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Komarov, T. N., M. V. Belova, D. D. Stolyarova, I. E. Shohin, D. S. Bogdanova, O. A. Miskiv, Yu V. Medvedev e I. M. Korenskaya. "Chemical and Toxicological Analysis of Antiretroviral Drugs". Drug development & registration 8, n.º 4 (26 de novembro de 2019): 53–60. http://dx.doi.org/10.33380/2305-2066-2019-8-4-53-60.
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Introduction. Human Immunodeficiency Virus (HIV) is one of the main socially significant infection all over the world. HIV-positive patients take medical care, including antiretroviral drugs (ARVs) pharmacotherapy. Like all drugs, ARVs have lots of side effects that should be taken when prescribing drugs as part of highly active antiretroviral therapy. There are many cases when side effects of ARVs caused patients to enter the toxicology department. Therefore, the development of new methods for the analysis of ARV in biological fluids for the timely diagnosis of treatment of poisoning of this group of drugs is relevant today.Aim. The aim of this study is development of screening analysis of atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in the urine to identify these drugs as possible toxicants for poisoning by high-performance liquid chromatography with tandem massselective detection (HPLC-MS/MS).Materials and methods. Identification of ARV was performed by HPLC-MS/MS. Methanol precipitation method was used as a sample preparation.Results and discussion. The optimal conditions for sample preparation, chromatographic separation, and mass-spectrometric detection were selected to determine the studied ARVs. This method was tested on urine samples from patients in the Department of Acute Poisoning and Somatopsychiatric Disorders (OOSPD) with acute ARV poisoning.Conclusion. This screening method for analyse atazanavir, abacavir, nevirapine, ritonavir, lopinavir, zidovudine, darunavir and efavirenz in human urine has been developed by HPLC-MS/MS. The developed method can be used to identify these drugs as possible toxicants in case of poisoning. The prospect for the development of the topic is the inclusion of new molecules in the method and quantitative determination of the studied ARVs.
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Matveev, A. V., A. E. Krasheninnikov, E. A. Egorova e E. I. Konyaeva. "Monitoring the safety of antiretroviral drugs in patients with HIV infection". HIV Infection and Immunosuppressive Disorders 13, n.º 1 (27 de abril de 2021): 115–23. http://dx.doi.org/10.22328/2077-9828-2021-13-1-115-123.
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The antiretroviral therapy is a lifelong use of a combination of three or more antiretroviral drugs (ARVDs). One of the factors contributing to a significant decrease in patients’ adherence to treatment is the high toxicity of ARVs.The aim of the study is to study the safety of antiretroviral drugs retrospectively and based on spontaneous reports about adverse drug reactions (ADRs) inputted in the ARCADe database.Materials and method. The objects of our research were the 649 spontaneous messages about ARVDs recorded in the regional electronic database (register) of spontaneous messages for period 01 January 2009 — 31 December 2018.Results. Most often, ADR were registered with the use of combined ARVD and non-nucleoside reverse transcriptase inhibitors. Zidovudine and Efavirenz were the leaders in terms of the incidence of ARV ADR. Among the combined anti-HIV drugs, the most frequently ADR were associated with the use of a Lamivudine and Zidovudine combination.Conclusion. Long-term use of ARVs requires regular monitoring of adverse reactions, which will improve the quality of life of patients with HIV infection and significantly increase their compliance with antiretroviral pharmacotherapy.
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Robinson, Jennifer A., Roxanne Jamshidi e Anne E. Burke. "Contraception for the HIV-Positive Woman: A Review of Interactions between Hormonal Contraception and Antiretroviral Therapy". Infectious Diseases in Obstetrics and Gynecology 2012 (2012): 1–15. http://dx.doi.org/10.1155/2012/890160.
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Background. Preventing unintended pregnancy in HIV-positive women can significantly reduce maternal-to-child HIV transmission as well as improve the woman’s overall health. Hormonal contraceptives are safe and effective means to avoid unintended pregnancy, but there is concern that coadministration of antiretroviral drugs may alter contraceptive efficacy.Materials and Methods. We performed a literature search of PubMed and Ovid databases of articles published between January 1980 and February 2012 to identify English-language reports of drug-drug interactions between hormonal contraceptives (HCs) and antiretroviral drugs (ARVs). We also reviewed the FDA prescribing information of contraceptive hormone preparations and antiretrovirals for additional data and recommendations.Results. Twenty peer-reviewed publications and 42 pharmaceutical package labels were reviewed. Several studies of combined oral contraceptive pills (COCs) identified decreased serum estrogen and progestin levels when coadministered with certain ARVs. The contraceptive efficacy of injectable depot medroxyprogesterone acetate (DMPA) and the levonorgestrel intrauterine system (LNG-IUS) were largely unaffected by ARVs, while data on the contraceptive patch, ring, and implant were lacking.Conclusions. HIV-positive women should be offered a full range of hormonal contraceptive options, with conscientious counseling about possible reduced efficacy of COCs and the contraceptive implant when taken with ARVs. DMPA and the LNG-IUS maintain their contraceptive efficacy when taken with ARVs.
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Satyanarayana, Kanikaram, e Sadhana Srivastava. "Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) – A Strategic Option for India". Open AIDS Journal 4, n.º 1 (19 de janeiro de 2010): 41–53. http://dx.doi.org/10.2174/1874613601004020041.
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The current HIV/AIDS scenario in India is quite grim with an estimated 2.4 million people living with HIV/AIDS (PLHA) in 2008, just behind South Africa and Nigeria. The anti-retroviral drugs (ARVs) remain the main stay of global HIV/AIDS treatment. Over 30 ARVs (single and FDCs) available under six categories viz., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), Protease inhibitors, the new Fusion inhibitors, Entry inhibitors-CCR5 co-receptor antagonists and HIV integrase strand transfer inhibitors. The major originator companies for these ARVs are: Abbott, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Gilead, GlaxoSmithKline (GSK), Merck, Pfizer, Roche, and Tibotec. Beginning with zidovidine in 1987, all the drugs are available in the developed countries. In India, about 30 ARVs are available as generics manufactured by Aurobindo, Hyderabad, Andhra Pradesh; Cipla Limited, Goa; Emcure Pharmaceuticals, Pune, Maharashtra; Hetero Drugs, Hyderabad, Andhra Pradesh; Macleods Pharmaceuticals, Daman; Matrix Laboratories, Nashik, Maharashtra; Ranbaxy, Sirmour, Himachal Pradesh; and Strides Arcolab, Bangalore, Karnataka. The National AIDS Control Organization (NACO) set up in 1992 by the Govt. of India provides free ARVs to HIV positive patients in India since 2004. The drugs available in India include both single drugs and FDCs covering both first line and second line ARVs. Even while there are claims of stabilization of the disease load, there is still huge gap of those who require ARVs as only about 150,000 PLHA receive the ARVs from the Govt. and other sources. Access to ARVs therefore is still a cause of serious concern ever since India became fully Trade Related Aspects of Intellectual Property Rights (TRIPS)-complaint in 2005. Therefore, the Indian pharmaceutical companies cannot make generics for those for drugs introduced post-2005 due to product patent regime. Other concerns include heat stable, other better formulations and second line ARVs for adults and more drugs and formulations for paediatric groups, that are still to be widely available in India and other developing countries. To examine whether strong intellectual property (IP) protection systems are to be considered important barriers for the limited or lack of access to ARVs, we studied the patent profile of the ARVs of the originator companies within and outside India. We could record 93 patents in the United States Patent & Trademark Office (USPTO). The originator companies have been also aggressively filing and enforcing patents in India. There have been a few efforts by companies like Gilead and GSK to grant licenses to generic manufacturers in developing countries, ostensibly to promote access to ARVs through lower (two-tier) pricing. These steps are considered as too little and too late. There is an urgent need to look for alternative strategies to promote access to ARVs both linked to and independent of IPRs. Patent pooling as a viable strategy mooted by the UNITAID should be seriously explored to promote access to ARVs. India is ideally suited for trying out the patent pool strategy as most of the global requirement of affordable ARV drugs for HIV/AIDS treatment is sourced from Indian generic companies.
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Bwalya, Edgar. "The Political Economy of Antiretroviral Drugs in Zambia". Perspectives on Global Development and Technology 5, n.º 4 (2006): 385–409. http://dx.doi.org/10.1163/156915006779206042.
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AbstractAccording to the 2005 United Nations Programe on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) Report, Zambia has one of the highest rates of HIV/AIDS cases in Southern Africa as well as in the world. However, it is also one of the few countries that have recorded a drop in the infection rates from an estimated 26% of the population in 2000 to just fewer than 16% in 2005. There appears to be a general consensus that the availability and free provision of antiretroviral drugs (ARVs) and treatment have raised hope that the recipients will live a longer, improved, and productive life. This paper will attempt to assess the major challenges to scaling-up antiretroviral therapy in Zambia. It argues that, while the government has made some progress in scaling-up access to ARVs, there is still much to be done.
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Scheffer, Mario Cesar. "Interaction between pharmaceutical companies and physicians who prescribe antiretroviral drugs for treating AIDS". Sao Paulo Medical Journal 132, n.º 1 (2014): 55–60. http://dx.doi.org/10.1590/1516-3180.2014.1321609.
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CONTEXT AND OBJECTIVE: Given that Brazil has a universal public policy for supplying medications to treat HIV and AIDS, the aim here was to describe the forms of relationship between physicians and the pharmaceutical companies that produce antiretrovirals (ARVs). DESIGN AND SETTING: Cross-sectional epidemiological study conducted in the state of São Paulo. METHODS : Secondary database linkage was used, with structured interviews conducted by telephone among a sample group of 300 physicians representing 2,361 professionals who care for patients with HIV and AIDS. RESULTS : Around two thirds (64%) of the physicians prescribing ARVs for HIV and AIDS treatment in the state of São Paulo who were interviewed declared that they had some form of relationship with pharmaceutical companies, of which the most frequent were receipt of publications (54%), visits by sales promoters (51%) and receipt of small-value objects (47%). CONCLUSIONS: Two forms of relationship between the pharmaceutical industry and physicians who deal with HIV and AIDS can be highlighted: facilitation of professionals' access to continuing education; and antiretroviral drug brand name promotion.
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Ndoboli, Dickson, Fredrick Nganga, Ben Lukuyu, Barbara Wieland, Delia Grace, Amrei von Braun e Kristina Roesel. "The misuse of antiretrovirals to boost pig and poultry productivity in Uganda and potential implications for public health". January-July 7, n.º 1 (7 de abril de 2021): 88–95. http://dx.doi.org/10.14202/ijoh.2021.88-95.
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Background and Aim: Since 2015, local newspapers reported that pig and poultry farmers in Uganda use antiretroviral drugs (ARVs) to promote growth in animals and control diseases. This study was conducted to assess farmers' knowledge, attitude and perceptions about the use of antiretroviral drugs as boosters in pigs and poultry and the possibility of detecting the antiretroviral drugs in meat using available laboratory methods. Materials and Methods: In 2019, a cross-sectional study was conducted in ten districts in Uganda. In 20 focus group discussions with 100 pig and poultry farmers and 70 animal health service providers, we assessed the use of ARV in livestock enterprises. Subsequently, samples of chicken, pigs, and animal feeds were collected from volunteer participants, and screened for residues of saquinavir, lopinavir, nevirapine, and efavirenz using liquid chromatography-tandem mass spectrophotometer. Results: Participants in all ten districts were predominantly smallholder farmers supplying the local markets. All groups reported the use of ARVs in pigs and broiler birds but not in layer hens. In the absence of good quality feeds, the motivation for feeding ARVs was rapid animal weight gain, as well as the control of animal diseases, for which farmers have no alternative solutions. ARVs were obtained within the community for free, against cash, or in-kind payment. Residues of lopinavir were detected in four, and saquinavir in seven districts, and all three sample matrices. Conclusion: Our study findings confirm anecdotal news reports on ARV use in livestock. While our findings are not generalizable to the whole country, they call for a representative follow-up. As the drugs were detected in tissues destined for human consumption, the potential risk to human health warrants further investigation.
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Hodel, E. M., C. Marzolini, C. Waitt e N. Rakhmanina. "Pharmacokinetics, Placental and Breast Milk Transfer of Antiretroviral Drugs in Pregnant and Lactating Women Living with HIV". Current Pharmaceutical Design 25, n.º 5 (3 de junho de 2019): 556–76. http://dx.doi.org/10.2174/1381612825666190320162507.
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Background:Remarkable progress has been achieved in the identification of HIV infection in pregnant women and in the prevention of vertical HIV transmission through maternal antiretroviral treatment (ART) and neonatal antiretroviral drug (ARV) prophylaxis in the last two decades. Millions of women globally are receiving combination ART throughout pregnancy and breastfeeding, periods associated with significant biological and physiological changes affecting the pharmacokinetics (PK) and pharmacodynamics (PD) of ARVs. The objective of this review was to summarize currently available knowledge on the PK of ARVs during pregnancy and transport of maternal ARVs through the placenta and into the breast milk. We also summarized main safety considerations for in utero and breast milk ARVs exposures in infants.Methods:We conducted a review of the pharmacological profiles of ARVs in pregnancy and during breastfeeding obtained from published clinical studies. Selected maternal PK studies used a relatively rich sampling approach at each ante- and postnatal sampling time point. For placental and breast milk transport of ARVs, we selected the studies that provided ratios of maternal to the cord (M:C) plasma and breast milk to maternal plasma (M:P) concentrations, respectively.Results:We provide an overview of the physiological changes during pregnancy and their effect on the PK parameters of ARVs by drug class in pregnancy, which were gathered from 45 published studies. The PK changes during pregnancy affect the dosing of several protease inhibitors during pregnancy and limit the use of several ARVs, including three single tablet regimens with integrase inhibitors or protease inhibitors co-formulated with cobicistat due to suboptimal exposures. We further analysed the currently available data on the mechanism of the transport of ARVs from maternal plasma across the placenta and into the breast milk and summarized the effect of pregnancy on placental and of breastfeeding on mammal gland drug transporters, as well as physicochemical properties, C:M and M:P ratios of individual ARVs by drug class. Finally, we discussed the major safety issues of fetal and infant exposure to maternal ARVs.Conclusions:Available pharmacological data provide evidence that physiological changes during pregnancy affect maternal, and consequently, fetal ARV exposure. Limited available data suggest that the expression of drug transporters may vary throughout pregnancy and breastfeeding thereby possibly impacting the amount of ARV crossing the placenta and secreted into the breast milk. The drug transporter’s role in the fetal/child exposure to maternal ARVs needs to be better understood. Our analysis underscores the need for more pharmacological studies with innovative study design, sparse PK sampling, improved study data reporting and PK modelling in pregnant and breastfeeding women living with HIV to optimize their treatment choices and maternal and child health outcomes.
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Moss, John A., Amanda M. Malone, Thomas J. Smith, Sean Kennedy, Cali Nguyen, Kathleen L. Vincent, Massoud Motamedi e Marc M. Baum. "Pharmacokinetics of a Multipurpose Pod-Intravaginal Ring Simultaneously Delivering Five Drugs in an Ovine Model". Antimicrobial Agents and Chemotherapy 57, n.º 8 (10 de junho de 2013): 3994–97. http://dx.doi.org/10.1128/aac.00547-13.
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ABSTRACTMultipurpose technologies that simultaneously protect from sexually transmitted infections and unintended pregnancy are urgently needed. Pod-intravaginal rings (IVRs) formulated with the antiretroviral agents (ARVs) tenofovir, nevirapine, and saquinavir and the contraceptives etonogestrel and estradiol were evaluated in sheep. Steady-state concentrations were maintained for 28 days with controlled, sustained delivery. This proof-of-principle study demonstrates that pod IVRs can deliver three ARVs from different mechanistic classes and a progestin-estrogen combination over the wide range needed for putative preventative efficacy.
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Anker, J. N. Y. van den, S. Sanduja, Kathleen Ferrer, N. Rakhmanina e Marc Pfister. "NOVEL APP FOR PRACTICAL DOSING OF COMBINATION ANTIRETROVIRAL THERAPY IN PEDIATRIC PATIENTS WITH HIV/AIDS". Archives of Disease in Childhood 101, n.º 1 (14 de dezembro de 2015): e1.20-e1. http://dx.doi.org/10.1136/archdischild-2015-310148.27.
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BackgroundCombination antiretroviral therapy (ART) of HIV infection in pediatric patients requires lifetime daily administration of a minimum of three antiretroviral drugs (ARVs). A wide range of dosing regimens is used in these patients. Dosing errors are common and may result in ARVs overdosing with associated toxicities orARVs underdosing resulting in the development of viral resistance. Attempts have been made to produce compact ARVs dosing charts, but have not been successful due to the complexity of regimens, ARV drug-drug interactions and compatibility restrictions. Advances in mobile technology have brought new opportunities for creating dosing support tools, including smartphone applications (Apps). In middle and low income countries, most affected by HIV epidemic,smartphones and tablets are widespread among medicalprofessionals. A mobile Appthat produces correct pediatric ARVs dosing, warnings for compatibility and most important drug interactions,has the potential to significantly improve the quality of ART in HIV-infected children.MethodsUsing reference ARVs guidelines from the 2014 Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection by the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children and 2013 World Health Organization pediatric HIV treatment guidelines we have developed a novel drug prescription App for pediatric ART.ResultsA noveldrug prescription App, based on up to date references, permits health care providers to easily access up-to-date dosing information and quickly calculate individualdoses of all ARVsbased on a patient's characteristics (e.g. weight, height, age, serum creatinine value). Most importantly, the App can be easily updated and synchronized remotely, allowing for timelydelivery of most important pediatric ARVs dosing updates.ConclusionThe smartphone App for pediatric ARVs can serve as an important healthcare worker support tool in the treatment of HIV-infected infants and children. Pharmacometric modelingcan be built in such App to leverage resistance and clinical patient data, individualize dosing strategies particularly for co-morbidities and optimize ART outcome. Most importantly, in the era of the global scale up of pediatric ART and task shifting of ART management to nursing staff, this App can have significant capacitating effect on the healthcare workforce.
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Cruz, Camille Carvalho Peixoto, Sóstenes Mistro, Carlos Maurício Cardeal Mendes, Robert Turner Schooley e Roberto José da Silva Badaró. "Monitoring of Delay to Pharmacy Refill in Assessing Adherence to Antiretroviral Therapy". Journal of Pharmacy Practice 33, n.º 2 (20 de agosto de 2018): 158–63. http://dx.doi.org/10.1177/0897190018795339.
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Background: Adherence to antiretroviral (ARV) therapy remains a major challenge in HIV therapeutics. Objective: To assess the adherence to ARV therapy by measuring the delay in monthly refilling of ARV drugs using pharmacy records and to correlate this with HIV plasma RNA measurements and CD4+ cell count. Method: Records of 170 HIV-positive patients were examined to identify HIV viral load (VL)/CD4+ results and the time interval to refill ARVs at the pharmacy. The correlation between the number of days missed to refill ARVs and plasma HIV-RNA detectability/CD4+ count was performed using the Spearman’s correlation coefficient ( r). Results: Fewer days missed to refill ARV was positively correlated with undetectable VL and increase in CD4+ count ( r = 0.407 and 0.237, respectively). Increase in adherence was correlated with longer retention in the cohort ( r = 0.208). Conclusion: Monitoring the delay to pick up ARVs from the pharmacy can be an important and simple tool to identify patients requiring assessment of their adherence.
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Kebede, T. G., MB Seroto, R. C. Chokwe, S. Dube e M. M. Nindi. "Adsorption of antiretroviral (ARVs) and related drugs from environmental wastewaters using nanofibers". Journal of Environmental Chemical Engineering 8, n.º 5 (outubro de 2020): 104049. http://dx.doi.org/10.1016/j.jece.2020.104049.
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Angira, Francis, Eucabeth Awuonda, Jacinter Oruko, Oyaro Boaz, Elijah Asadhi e George Olilo. "PO 8595 FACTORS ASSOCIATED WITH VIROLOGIC FAILURE AMONG WOMEN WITH PRIOR EXPOSURE TO ANTIRETROVIRAL DRUGS FOR PMTCT, KISUMU, KENYA". BMJ Global Health 4, Suppl 3 (abril de 2019): A60.3—A61. http://dx.doi.org/10.1136/bmjgh-2019-edc.159.
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BackgroundUse of antiretroviral drugs (ARVs) for a discrete period for Preventing Mother-to-Child HIV transmission (PMTCT) only may be compared to Structured Treatment Interruption, which has been associated with virologic failure (VF). We sought to determine factors associated with VF among women on Antiretroviral Therapy (ART) but with prior exposure to short-term ARVs for PMTCT.MethodsHIV-infected women presenting for ART initiation in three HIV care clinics in Kisumu County, Kenya were enrolled in the KiBS follow-up study (2010–2013) if they had previously received triple ARVs for PMTCT (Group 1) or short-course ARVs for PMTCT (Group 2) or were ARVs-naïve (Group 3). First-line ART was provided as per 2010 WHO treatment guidelines and viral load (VL) tests were conducted every six months for 24 months. VF was defined as any confirmed VL value ≥400 copies/ml after 6 months of ART initiation. Frequencies and proportions were used in the descriptive analysis while Pearson’s Chi-square/Fisher’s exact test was used to determine the association between VF and eight independent variables. Univariate and Multivariate Cox-proportional regression model was fitted to investigate factors associated with VF.ResultsOut of 284 participants data for 245 were analysed (Group 1: 27; Group 2: 107; Group 3: 111). Majority were aged 25–29 years and over 60% had primary/lesser education. There were 39 (Group 1: 5; Group 2: 16; Group 3: 18) VFs with a total VF incidence of 8.12 [95% CI (5.96, 11.17)] per 1000 Person months of observation (PMOs). Group 2 had the lowest VF incidence. Baseline CD4 <349 cells/mm3 and initiation/use of TDF/3TC/EFV were associated with virologic failure (VF).ConclusionWomen at risk of VF based on the identified risk factors should be identified and targeted with appropriate intervention. Further studies are needed to verify and understand the mechanisms of association between VF and TDF/3TC/EFV which is a WHO-recommended first-line ART regimen.
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Chahal, Harinder Singh, Peter Capella, Ryan Presto, Jeffrey S. Murray, Martin Shimer, Mary Lou Valdez e Peter G. Lurie. "Impact of the US Food and Drug Administration registration of antiretroviral drugs on global access to HIV treatment". BMJ Global Health 3, n.º 3 (maio de 2018): e000651. http://dx.doi.org/10.1136/bmjgh-2017-000651.
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BackgroundSince 2004, the US Food and Drug Administration’s (USFDA) dedicated drug review process in support of President’s Emergency Plan for AIDS Relief (PEPFAR) has made safe, effective and quality antiretrovirals (ARVs) available for millions of patients. Furthermore, the WHO and Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) can add the USFDA-reviewed products to their respective formularies, through a novel process of ‘one-way reliance’. We assessed the number of ARVs made available through WHO and Global Fund based on the USFDA review.MethodsWe conducted a cross-sectional study of all the USFDA-reviewed PEPFAR drugs between 1 December 2014 and 20 March 2017 to determine 1) the percentage that are included on the WHO and Global Fund formularies; 2) the number of the USFDA ARVs supporting the WHO HIV treatment guidelines, and their uptake by WHO and Global Fund and 3) time between the USFDA review and WHO review of the same ARVs.FindingsOverall, 91% (204/224) of the USFDA products appeared on either the WHO/Prequalification of Medicines Programme (PQP) or the Global Fund ARV lists. Forty-five per cent (100/224) and 83% (184/224) appear on WHO/PQP and Global Fund formularies through one-way reliance, respectively. Forty-one per cent (91/224) of the USFDA products support the WHO-preferred first-line HIV treatment options. Of these 91 products, 38% and 85% of products were adopted by WHO/PQP and Global Fund through one-way reliance, respectively. Sixty-six products that were fully reviewed and registered by WHO (vs one-way reliance) had also undergone the USFDA review; 46 of these were registered by WHO after the USFDA review was complete (median delay of 559 days (IQR 233–798 days)).ConclusionsThe USFDA’s PEPFAR process is making safe and effective ARVs available worldwide, in part because the major global ARV procurement organisations rely on the USFDA registration as proof of quality. There is room for improved information sharing and collaboration to reduce duplication of effort, save resources and further expedite access to ARVs.
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Sanchez, Ana B., Giuseppe P. Varano, Cyrus M. de Rozieres, Ricky Maung, Irene C. Catalan, Cari C. Dowling, Natalia E. Sejbuk, Melanie M. Hoefer e Marcus Kaul. "Antiretrovirals, Methamphetamine, and HIV-1 Envelope Protein gp120 Compromise Neuronal Energy Homeostasis in Association with Various Degrees of Synaptic and Neuritic Damage". Antimicrobial Agents and Chemotherapy 60, n.º 1 (19 de outubro de 2015): 168–79. http://dx.doi.org/10.1128/aac.01632-15.
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ABSTRACTHIV-1 infection frequently causes HIV-associated neurocognitive disorders (HAND) despite combination antiretroviral therapy (cART). Evidence is accumulating that components of cART can themselves be neurotoxic upon long-term exposure. In addition, abuse of psychostimulants, such as methamphetamine, seems to aggravate HAND and compromise antiretroviral therapy. However, the combined effect of virus and recreational and therapeutic drugs on the brain is poorly understood. Therefore, we exposed mixed neuronal-glial cerebrocortical cells to antiretrovirals (ARVs) (zidovudine [AZT], nevirapine [NVP], saquinavir [SQV], and 118-D-24) of four different pharmacological categories and to methamphetamine and, in some experiments, the HIV-1 gp120 protein for 24 h and 7 days. Subsequently, we assessed neuronal injury by fluorescence microscopy, using specific markers for neuronal dendrites and presynaptic terminals. We also analyzed the disturbance of neuronal ATP levels and assessed the involvement of autophagy by using immunofluorescence and Western blotting. ARVs caused alterations of neurites and presynaptic terminals primarily during the 7-day incubation and depending on the specific compounds and their combinations with and without methamphetamine. Similarly, the loss of neuronal ATP was context specific for each of the drugs or combinations thereof, with and without methamphetamine or viral gp120. Loss of ATP was associated with activation of AMP-activated protein kinase (AMPK) and autophagy, which, however, failed to restore normal levels of neuronal ATP. In contrast, boosting autophagy with rapamycin prevented the long-term drop of ATP during exposure to cART in combination with methamphetamine or gp120. Our findings indicate that the overall positive effect of cART on HIV infection is accompanied by detectable neurotoxicity, which in turn may be aggravated by methamphetamine.
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Giancola, Maria Letizia, Patrizia Lorenzini, Antonella Cingolani, Francesco Baldini, Simona Bossolasco, Teresa Bini, Laura Monno et al. "Virological Response in Cerebrospinal Fluid to Antiretroviral Therapy in a Large Italian Cohort of HIV-Infected Patients with Neurological Disorders". AIDS Research and Treatment 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/708456.
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The aim of the present study was to analyse the effect of antiretroviral (ARV) therapy and single antiretroviral drugs on cerebrospinal fluid (CSF) HIV-RNA burden in HIV-infected patients affected by neurological disorders enrolled in a multicentric Italian cohort. ARVs were considered “neuroactive” from literature reports. Three hundred sixty-three HIV-positive patients with available data from paired plasma and CSF samples, were selected. One hundred twenty patients (33.1%) were taking ARVs at diagnosis of neurological disorder. Mean CSF HIV-RNA was significantly higher in naïve than in experienced patients, and in patients not taking ARV than in those on ARV. A linear correlation between CSF HIV-RNA levels and number of neuroactive drugs included in the regimen was also found (r=−0.44,P<0.001). Low -plasma HIV-RNA and the lack of neurocognitive impairment resulted in independently associated to undetectable HIV-RNA. Taking nevirapine or efavirenz, or regimen including NNRTI, NNRTI plus PI or boosted PI, was independently associated to an increased probability to have undetectable HIV-RNA in CSF. The inclusion of two or three neuroactive drugs in the ARV regimen was independently associated to undetectable viral load in CSF. Our data could be helpful in identifying ARV regimens able to better control HIV replication in the CNS sanctuary, and could be a historical reference for further analyses.
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Kieran, Jennifer A., Eimear O’Reilly, Siobhan O’Dea, Colm Bergin e Aisling O’Leary. "Generic substitution of antiretrovirals: patients’ and health care providers’ opinions". International Journal of STD & AIDS 28, n.º 12 (2 de março de 2017): 1239–46. http://dx.doi.org/10.1177/0956462417696215.
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There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients’ and providers’ knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.
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Satyanarayana, Kanikaram. "Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India". Open AIDS Journal 4, n.º 1 (19 de janeiro de 2010): 41–53. http://dx.doi.org/10.2174/1874613601004010041.
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Satyanarayana, Kanikaram. "Patent Pooling for Promoting Access to Antiretroviral Drugs (ARVs) - A Strategic Option for India". Open AIDS Journal 4, n.º 1 (1 de fevereiro de 2010): 41–53. http://dx.doi.org/10.2174/1874120701004010041.
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Stader, Felix, Hannah Kinvig, Manuel Battegay, Saye Khoo, Andrew Owen, Marco Siccardi e Catia Marzolini. "Analysis of Clinical Drug-Drug Interaction Data To Predict Magnitudes of Uncharacterized Interactions between Antiretroviral Drugs and Comedications". Antimicrobial Agents and Chemotherapy 62, n.º 7 (23 de abril de 2018): e00717-18. http://dx.doi.org/10.1128/aac.00717-18.
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ABSTRACTDespite their high potential for drug-drug interactions (DDI), clinical DDI studies of antiretroviral drugs (ARVs) are often lacking, because the full range of potential interactions cannot feasibly or pragmatically be studied, with some high-risk DDI studies also being ethically difficult to undertake. Thus, a robust method to screen and to predict the likelihood of DDIs is required. We developed a method to predict DDIs based on two parameters: the degree of metabolism by specific enzymes, such as CYP3A, and the strength of an inhibitor or inducer. These parameters were derived from existing studies utilizing paradigm substrates, inducers, and inhibitors of CYP3A to assess the predictive performance of this method by verifying predicted magnitudes of changes in drug exposure against clinical DDI studies involving ARVs. The derived parameters were consistent with the FDA classification of sensitive CYP3A substrates and the strength of CYP3A inhibitors and inducers. Characterized DDI magnitudes (n= 68) between ARVs and comedications were successfully quantified, meaning 53%, 85%, and 98% of the predictions were within 1.25-fold (0.80 to 1.25), 1.5-fold (0.66 to 1.48), and 2-fold (0.66 to 1.94) of the observed clinical data. In addition, the method identifies CYP3A substrates likely to be highly or, conversely, minimally impacted by CYP3A inhibitors or inducers, thus categorizing the magnitude of DDIs. The developed effective and robust method has the potential to support a more rational identification of dose adjustment to overcome DDIs, being particularly relevant in an HIV setting, given the treatment's complexity, high DDI risk, and limited guidance on the management of DDIs.
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Matthew, Anyanwu. "A descriptive study of HIV positive pregnant mothers on antiretroviral drugs (ARVS) in the Gambian tertiary hospital". International Journal of Pregnancy & Child Birth 6, n.º 4 (11 de agosto de 2020): 93–97. http://dx.doi.org/10.15406/ipcb.2020.06.00204.
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Background:/Aims: The use of antiretroviral drugs (ARVs) in pregnancy has shown remarkable improvement in immune status and have revolutionized the approach of care to people living with HIV (PLHIV). Some adverse pregnancy conditions have been reported which may depend on type of regimen, time and duration of use. The use of ARVs in pregnancy have been dynamic and transition from one regimen to the other have setting and country based variations. Therefore, knowing the impact of ARVs in pregnancy among PLHIV in our settings deserve evidence based information. Methods: Pregnant women attending antenatal clinic at the hospital were prospectively recruited and followed up. HIV positive mothers were recruited irrespective of gestation age. At the time of delivery, obstetric and neonatal characteristics were entered into computer database. Mothers and their children were followed until 6 weeks postpartum. The data was analyzed with Epi-info version 7.1.5. Chi square at significant level of 0.05 and confidence level of 95% was used to determine significance. Results: A total of 55 HIV positive mothers were in the study. The age range was between 18 to 45 years and parity was 0 to 8. The mean birth weight and gestation age at delivery was 2.92kg (SD 0.556) and 36 weeks (SD 2.8 weeks) respectively. The absolute CD4 count of 500cells/mm3 and above (43.3%) was associated with no low birth weight. The mean glycaemic results were within normal range, 4.02-4.75 and 5.00-6.79 Mmol/l pre and post prandial respectively. Conclusion: Low birth weight was not associated with HAART in pregnancy and good immune condition was not associated with low birth weight. There was no association of protease inhibitors and gestational diabetes mellitus.
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Dionisio, Daniele, Vincenzo Racalbuto e Daniela Messeri. "Designing ARVs Patent Pool Up to Trade & Policy Evolutionary Dynamics". Open AIDS Journal 4, n.º 1 (19 de janeiro de 2010): 70–75. http://dx.doi.org/10.2174/1874613601004020070.
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Patent pools for second and third-line Fixed Dose Combination (FDC) antiretroviral drugs (ARVs) should not be delayed as they are instrumental to urgent public health needs in the under-served markets. Nonetheless, multinational originator companies still seem to perceive patent pooling for ARVs as a minefield that would offer the generic competitors lots of deeply exploitable opportunities, to the detriment of patent owner’s rights. This paper analyses the brand industry concerns, while looking for a strategy up to a really equitable and free world market, without any discrimination between end-users in wealthy and resource-limited countries. This strategy would urge partnerships between originator companies first to make newer FDC ARVs quickly available and allow patent pool agreements with generic counterparts to be negotiated straight afterwards. The patent pool strategy highlighted in this paper would assert the primacy of health over for-profit policies, while aligning with the 61st WHO’s Assembly recommendations and G7, G8 and World Trade Organisation’s warnings and pledges against trade protectionism.
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Avery, L. B., N. Sacktor, J. C. McArthur e C. W. Hendrix. "Protein-Free Efavirenz Concentrations in Cerebrospinal Fluid and Blood Plasma Are Equivalent: Applying the Law of Mass Action To Predict Protein-Free Drug Concentration". Antimicrobial Agents and Chemotherapy 57, n.º 3 (7 de janeiro de 2013): 1409–14. http://dx.doi.org/10.1128/aac.02329-12.
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ABSTRACTEfavirenz (EFV) is one of the most commonly prescribed antiretroviral drugs (ARVs) for the treatment of HIV. Highly protein-bound drugs, like EFV, have limited central nervous system (CNS) penetration when measured using total drug concentration gradients between blood plasma (BP) and cerebrospinal fluid (CSF). However, the more relevant pharmacologically active protein-free drug concentrations are rarely assessed directly in clinical studies. Using paired BP and CSF samples obtained from 13 subjects on an EFV-containing regimen, both the protein-free and total concentrations of EFV were determined. Despite a median (interquartile range [IQR]) total EFV BP/CSF concentration ratio of 134 (116 to 198), the protein-free EFV BP/CSF concentration ratio was 1.20 (0.97 to 2.12). EFV median (IQR) protein binding was 99.78% (99.74 to 99.80%) in BP and 76.19% (74.47 to 77.15%) in CSF. In addition, using the law of mass action and anin vitro-derived EFV-human serum albumin dissociation constant, we have demonstrated that the predicted median (IQR) protein-free concentration in BP, 4.59 ng/ml (4.02 to 9.44 ng/ml), compared well to that observed in BP, 4.77 ng/ml (3.68 to 6.75 ng/ml). Similar results were also observed in CSF and seminal plasma. This method provides a useful predictive tool for estimating protein binding in varied anatomic compartments. Our results of equivalent protein-free EFV concentrations in BP and CSF do not support prior concerns of the CNS as a pharmacological sanctuary from EFV. As CSF penetration of ARVs may increase our understanding of HIV-associated neurological dysfunction and antiretroviral effect, assessment of protein-free CSF concentrations of other highly protein-bound ARVs is warranted.
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Maulidya Sari, Aisha, Ika Ratna Hidayati e Rizka Novia Atmadani. "The Relationship between The Level of Side Effects of ARV Drugs in ODHA Patients to The Level of The Compliance Use of ARV Drugs". Pharmaceutical Journal of Indonesia 6, n.º 2 (30 de junho de 2021): 125–29. http://dx.doi.org/10.21776/ub.pji.2021.006.02.8.
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HIV or Human Immunodeficiency Virus is one of the causes of AIDS ( Acquired Immunodeficiency Syndrome) that is a disease that attacks the body's immunity. One therapy for treating HIV/AIDS is with antiretroviral therapy. In antiretroviral therapy high adherence is needed at least 95% of the dose should not be forgotten to achieve desired virological suppression. One factor affecting compliance is the side effects of ARV drugs that appear in ODHA patients undergoing antiretroviral therapy. This study aims at knowing the relationship of the level of drug side effects to the level of compliance in the treatment of ARVs in ODHA patients. This research uses cross-sectional in ODHA patients in Puskesmas Dinoyo, Malang City. The results of the study were found that the level of ODHA patient drug side effects at the Puskesmas Dinoyo VCT Clinic, the ODHA patient who did not experience side effects, was 5.8% , side effects a little 21.3%, moderate side effects 21.2% and high side effects 51.8%. Compliance with taking ODHA patient medication at the VCT Clinic Puskesmas Dinoyo patients with low adherence of 1.2%, moderate compliance 69.4% and high compliance 29.4%. There is no significant relationship between the level of side effects of ARV drugs in ODHA patients with the level of compliance with ARV drug use with values p- the value obtained is 0.412.
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Kwobah, Charles M., Kara K. Wools-Kaloustian, Jane N. Gitau e Abraham M. Siika. "Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups". Case Reports in Medicine 2012 (2012): 1–5. http://dx.doi.org/10.1155/2012/698513.
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Mycobacteria leprae(leprosy)and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population) of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs); medications’ side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART). We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART) and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient.
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Manowati, Lilik, Purwaningsih Purwaningsih e Abu Bakar. "Perception of People Living With HIV/AIDS Affecting Lost to Follow-Up of ARV Therapy". Critical Medical and Surgical Nursing Journal 8, n.º 1 (26 de junho de 2019): 31. http://dx.doi.org/10.20473/cmsnj.v8i1.12403.
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ABSTRACTIntroduction: HIV/AIDS sufferers must consume antiretrovirals every day and control routinely each month to take ARVs in the hospital. The condition make patients having a risk of lost to follow up attitude. The purpose of this study was to determine the factors related to the attitude of lost to follow-up on people living with hiv/aids with arv therapy at rsud dr. soetomo surabaya. Method: This study used descriptive correlation design with a cross-sectional approach. The population were 135 patients and 100 patients were required as research participant with consequtive sampling. Independent variables were perceived susceptibility, perceived severity, perceived barrier to action, perceived benefits of action, cues to action, and self efficacy. The dependent variable was lost to follow up behavior. Data were obtained by questionnaire and analyzed with Spearman's Rho. Result: There was a relationship between perceived susceptability (p=0.002), perceived severity (p=0.025), perceived barrier to action (p=0.022) and cues to action (p=0.011) with lost to follow-up behavior. There was no correlation between perceived benefit of action (p=0.196) and self efficacy (p=0.071) with lost to follow-up behavior. Discussion: Knowledge and awareness regarding the importance taking antiretroviral drugs regularly and control routinely needs to be increased for patients with antiretroviral drugs. Further researchers are advised to conduct in-depth research (qualitative research) related to the causes of lost to follow-up behaviour thus.
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Khairunisa, Siti Qamariyah, Irine Normalina e Nasronudin Nasronudin. "EVALUATION ON THE NUMBER OF CD4 T CELLS AND ANTIRETROVIRAL SIDE EFFECTS IN PATIENTS WITH AIDS". Indonesian Journal of Tropical and Infectious Disease 3, n.º 2 (20 de junho de 2016): 96. http://dx.doi.org/10.20473/ijtid.v3i2.213.
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Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occur within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy and side effects arising during the taking of ARVs. Samples were collected from 10 patients infected by HIV/AIDS in a clinic in Surabaya. This study is an analytical survey. Data collection was conducted using secondary data obtained from the medical record card status on HIV paients in a clinic in Surabaya. Data results showed that the side effects that often occur in people with AIDS are appetite loss (90%), headache (80%), insomnia (80%) and nausea (70%). While many combinations of antiretroviral drugs have side effects such as a combination of AZT +3 TC + EFV, d4T +3 TC + followed by EFV and AZT +3 TC + NVP. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cellsin patients living with HIV, as shown by the tendency of an increase in the number of CD4 T-cells in 8 out of 10 AIDS patients who received a antiretroviral therapy.
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Mutanga, Jane N., Simon Mutembo, Amara E. Ezeamama, Robert C. Fubisha, Derrick Sialondwe, Brenda Simuchembu, Macwani Mutukwa, Jelita Chinyonga, Philip E. Thuma e Christopher C. Whalen. "Tracking Progress Toward Elimination of Mother to Child Transmission of HIV in Zambia: Findings from the Early Infant Diagnosis of HIV Program (2009–2017)". Journal of Tropical Pediatrics 66, n.º 1 (14 de maio de 2019): 56–65. http://dx.doi.org/10.1093/tropej/fmz030.
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Abstract Background We carried out analyses of early infant testing results at Livingstone Central Hospital in Zambia to assess time of testing, linkages to care and availability of test results for clinical decision making. Methods We abstracted data from registers of HIV-exposed infants who had dried blood spots cards (DBS) collected for DNA-PCR from January 2009 to December 2017. Only those tested from 2014 to 2017 had additional data which were used to estimate risk factors for mother-to-child HIV transmission using logistic regression models. Results DBS were collected from 2630 children. The proportion of HIV-positive tests decreased from 21% in 2009 to 2% in 2016 and 2017. Median turnaround time for results was 9 weeks (IQR: 5, 15) for HIV-negative, 7 weeks (IQR: 5, 13) for HIV-positive children. Only 2% of infants whose mothers took antiretroviral therapy (ART) were HIV positive, while 18% of infants whose mothers took short course antiretroviral drugs (ARVs) were infected. Infants of mothers who did not take ARVs had 9 times the odds of an HIV positive test (OR = 8.9, 95% CI: 3.6, 22.6). Infants of mothers who received short course ARVs were 40% less likely to get an HIV test within the first 2 months of life (OR = 0.6, 95% CI: 0.4, 0.9) compared to infants of mothers who received ART. Only 52% had a third test at median age 52 weeks (IQR: 50, 54). Conclusions Long turnaround time for test results and low retention in care after the initial HIV test were critical challenges to clinical decision making.
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Anggriani, Ani, Ida Lisni e Olga Susana Liku. "POLA PENGGUNAAN OBAT ANTIRETROVIRAL (ARV) PADA RESEP PASIEN RAWAT JALAN DARI KLINIK HIV/AIDS SALAH SATU RUMAH SAKIT SWASTA DI KOTA BANDUNG". Jurnal Riset Kefarmasian Indonesia 1, n.º 1 (19 de janeiro de 2019): 64–81. http://dx.doi.org/10.33759/jrki.v1i1.10.
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ABSTRACT
The Human Immunodeficiency Virus (HIV) continues to be a major global public health issue, which targets the human immune system. The using of ARVs in the treatment of HIV / AIDS increased life expectancy for PLHIV (People With HIV / AIDS). This study aims to determine the description of the using of ARV drugs in outpatients of the HIV / AIDS Clinic and assessed their suitability with established treatment standards. This research was carried out in a descriptive non-experimental manner, with data collection carried out retrospectively, used patient prescription data from April to December 2017. The results of quantitative studies showed 87% were male patients, and the largest age group was 20-29 years (39%) . Class of antiretroviral drugs used were Nucleoside / Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Protease Inhibitors (PI), with a combination of antiretroviral drugs most was the combination of first-line tenofovir + lamivudine + efavirenz (69%) while the second-line drug zidovudine + lamivudine + lopinavir / ritonavir was 1%. The most commonly used comorbid drug was cotrimoxazole. For qualitative data, the accuracy of combination and dose of ARV drugs was 100% in accordance with Permenkes No. 87/ 2014, with 79% of patients adhered to antiretroviral treatment every month. The potential for most ARV drug interactions with other drugs for the moderate category was zidovudin + cotrimoxazole (11%) which occured pharmacokinetically by decreasing renal clearance of zidovudine and glucuronide metabolites. In conclusion, the pattern of used of ARV drugs had met the standard of Permenkes No.87/2014, with the most used were the first line combination of tenofovir + lamivudine + efavirenz.
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Bakare, Adekunle A., Kehinde M. Akinseye, Bayonle A. Aminu, Francis C. Ofoegbu, Saheed O. Anifowose, Stork Abruda, Opeoluwa M. Fadoju et al. "Genetic and reproductive toxicity of lamivudine, tenofovir disoproxil fumarate, efavirenz and their combination in the bone marrow and testicular cells of male mice". Annals of Science and Technology 5, n.º 1 (1 de junho de 2020): 1–10. http://dx.doi.org/10.2478/ast-2020-0001.
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AbstractThe combination of antiretroviral (ARV) drugs: lamivudine, tenofovir disoproxil fumarate (TDF) and efavirenz is among the preferred first-line regimens for adolescents and adults infected with HIV. However, knowledge on in vivo genetic and reproductive toxicity of each of these drugs and their combination is limited. We evaluated the genotoxicity of lamivudine, TDF, efavirenz and their combination utilizing the mouse micronucleus (MN) and sperm morphology tests. Histopathological analysis of the testes of exposed mice was also carried out. 0.016, 0.032, 0.064 and 0.129 mg/kg bwt of lamivudine, TDF and the combination; and 0.032, 0.064, 0.129 and 0.259 mg/kg bwt of efavirenz corresponding to 0.125, 0.250, 0.500 and 1.000 x the human therapeutic daily dose (HTD) of each of the ARVs and their combinations were administered to mice for 5 consecutive days. Data on MN showed a significant increase (p < 0.05) across the tested doses of TDF, efavirenz and the combination, with the combination inducing lower frequency of MN than TDF and efavirenz. Lamivudine did not evoke significant induction of MN. Significant increase in frequency of abnormal sperm cells were observed in the tested samples, however, the combination induced the highest number of abnormal spermatozoa. The ARVs and their combination induced pathological lesions such as vacuolation and necrosis in mice testes. These findings suggest that the individual ARVs and their combination are potentially capable of activating genetic alterations in the bone marrow and germ cells of male mice thereby raising concern for long term use by HIV patients.
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Kramer, Victor G., Susan M. Schader, Maureen Oliveira, Susan P. Colby-Germinario, Daniel A. Donahue, Diane N. Singhroy, Randy Tressler, Richard D. Sloan e Mark A. Wainberg. "Maraviroc and Other HIV-1 Entry Inhibitors Exhibit a Class-Specific Redistribution Effect That Results in Increased Extracellular Viral Load". Antimicrobial Agents and Chemotherapy 56, n.º 8 (21 de maio de 2012): 4154–60. http://dx.doi.org/10.1128/aac.00409-12.
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ABSTRACTHIV entry inhibitors, such as maraviroc (MVC), prevent cell-free viruses from entering the cells. In clinical trials, patients who were treated with MVC often displayed viral loads that were above the limit of conventional viral load detection compared to efavirenz-based regimens. We hypothesize that viruses blocked by entry inhibitors may be redistributed to plasma, where they artificially increase viral load measurements compared to those with the use of antiretroviral drugs (ARVs) that act intracellularly. We infected PM-1 cells with CCR5-tropic HIV-1 BaL or CXCR4-tropic HIV-1 NL4-3 in the presence of inhibitory concentrations of efavirenz, raltegravir, enfuvirtide, maraviroc, and AMD3100, the latter three being entry inhibitors. Supernatant viral load, reverse transcriptase enzyme activity, and intracellular nucleic acid levels were measured at times up to 24 h postinfection. Infectivity of redistributed dual-tropic HIV-1 was assessed using TZM-bl cells. Extracellular viral load analysis revealed that entry inhibitor-treated cells had higher levels of virus in the supernatant than the cells treated with other ARVs at 8 h postinfection. By 24 h, the supernatant viral load was still higher for entry inhibitors than other ARVs. We observed a correlation between viral load and the step of entry inhibition. Dual-tropic virus infectivity was undiminished utilizing the CCR5 coreceptor following redistribution by CXCR4 entry inhibition. Thisin vitromodel indicates that entry inhibitors exhibit a redistribution effect unseen with intracellular ARV drugs. Based on these results, the effectiveness of some entry inhibitors may be underestimated if plasma viral load is used as a sole indicator of clinical success.
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Wainberg, Mark A., e Bluma G. Brenner. "The Impact of HIV Genetic Polymorphisms and Subtype Differences on the Occurrence of Resistance to Antiretroviral Drugs". Molecular Biology International 2012 (26 de junho de 2012): 1–10. http://dx.doi.org/10.1155/2012/256982.
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The vast majority of reports on drug resistance deal with subtype B infections in developed countries, and this is largely due to historical delays in access to antiretroviral therapy (ART) on a worldwide basis. This notwithstanding the concept that naturally occurring polymorphisms among different non-B subtypes can affect HIV-1 susceptibility to antiretroviral drugs (ARVs) is supported by both enzymatic and virological data. These findings suggest that such polymorphisms can affect both the magnitude of resistance conferred by some major mutations as well as the propensity to acquire certain resistance mutations, even though such differences are sometimes difficult to demonstrate in phenotypic assays. It is mandatory that tools are optimized to assure accurate measurements of drug susceptibility in non-B subtypes and to recognize that each subtype may have a distinct resistance profile and that differences in resistance pathways may also impact on cross-resistance and the choice of regimens to be used in second-line therapy. Although responsiveness to first-line therapy should not theoretically be affected by considerations of viral subtype and drug resistance, well-designed long-term longitudinal studies involving patients infected by viruses of different subtypes should be carried out.
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Barral, Maria F. M., Gisele R. de Oliveira, Rubens C. Lobato, Raul A. Mendoza-Sassi, Ana M. b. Martínez e Carla V. Gonçalves. "RISK FACTORS OF HIV-1 VERTICAL TRANSMISSION (VT) AND THE INFLUENCE OF ANTIRETROVIRAL THERAPY (ART) IN PREGNANCY OUTCOME". Revista do Instituto de Medicina Tropical de São Paulo 56, n.º 2 (abril de 2014): 133–38. http://dx.doi.org/10.1590/s0036-46652014000200008.
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In the absence of intervention, the rate of vertical transmission of HIV can range from 15-45%. With the inclusion of antiretroviral drugs during pregnancy and the choice of delivery route this amounts to less than 2%. However ARV use during pregnancy has generated several questions regarding the adverse effects of the gestational and neonatal outcome. This study aims to analyze the risk factors for vertical transmission of HIV-1 seropositive pregnant women living in Rio Grande and the influence of the use of ARVs in pregnancy outcome. Among the 262 pregnant women studied the rate of vertical transmission of HIV was found to be 3.8%. Regarding the VT, there was a lower risk of transmission when antiretroviral drugs were used and prenatal care was conducted at the referral service. However, the use of ART did not influence the outcome of pregnancy. However, initiation of prenatal care after the first trimester had an influence on low birth weight, as well as performance of less than six visits increased the risk of prematurity. Therefore, the risk factors analyzed in this study appear to be related to the realization of inadequate pre-natal and maternal behavior.
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D, Nthani, e Hamoonga Mwiinga Bona. "Investigating Treatment Literacy on Antiretroviral Drugs (ARVs) and Nutrient Interaction Among People Living with HIV/AIDS (PLHIV)". Acta Scientifci Nutritional Health 5, n.º 4 (20 de março de 2021): 30–48. http://dx.doi.org/10.31080/asnh.2020.05.0844.
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Lago, Regina Ferro do, e Nilson do Rosário Costa. "Antiretroviral manufacturers and the challenge of universal access to drugs through the Brazilian National STD/AIDS Program". Cadernos de Saúde Pública 25, n.º 10 (outubro de 2009): 2273–84. http://dx.doi.org/10.1590/s0102-311x2009001000017.
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This article describes the antiretroviral (ARV) manufacturing market in Brazil and contextualizes the challenges for the public policy of supplying ARVs through the National STD/AIDS Program. Increasing expenditure on these drugs is the main source of uncertainty for the policy's future. Brazil's domestic scenario is one of growing external dependence, both for the finished drugs and the active ingredients. Experience in the National Program has shown that it is the state's role to provide public goods, which presupposes ensuring mutual compatibility between company interests and social interests. This balance is currently at stake in Brazil, since structural changes in the market have raised challenges for the National Program's sustainability, requiring new public policy instruments in defense of the collective interest. The article drew on a literature review, using bibliographic indexing sources, systematic organization of primary data, government publications, relevant legislation, research reports, and articles recommended by experts from the field.
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Santos, André F. A., Denis M. Tebit, Matthew S. Lalonde, Ana B. Abecasis, Annette Ratcliff, Ricardo J. Camacho, Ricardo S. Diaz, Ottmar Herchenröder, Marcelo A. Soares e Eric J. Arts. "Effect of Natural Polymorphisms in the HIV-1 CRF02_AG Protease on Protease Inhibitor Hypersusceptibility". Antimicrobial Agents and Chemotherapy 56, n.º 5 (13 de fevereiro de 2012): 2719–25. http://dx.doi.org/10.1128/aac.06079-11.
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ABSTRACTHypersusceptibility (HS) to inhibition by different antiretroviral drugs (ARVs) among diverse HIV-infected individuals may be a misnomer because clinical response to treatment is evaluated in relation to subtype B infections while drug susceptibility of the infecting virus, regardless of subtype, is compared to a subtype B HIV-1 laboratory strain (NL4-3 or IIIB). Mounting evidence suggests that HS to different ARVs may result in better treatment outcome just as drug resistance leads to treatment failure. We have identified key amino acid polymorphisms in the protease coding region of a non-B HIV-1 subtype linked to protease inhibitor HS, namely, 17E and 64M in CRF02_AG. These HS-linked polymorphisms were introduced in the BD6-15 CRF02_AG molecular clone and tested for inhibition using a panel of protease inhibitors. In general, suspected HS-linked polymorphisms did increase susceptibility to specific protease inhibitors such as amprenavir and atazanavir, but the combination of the 17E/64M polymorphisms showed greater HS. These two mutations were found at low frequencies but linked in a sequence database of over 700 protease sequences of CRF02_AG. In direct head-to-head virus competitions, CRF02_AG harboring the 17E/64M polymorphisms also had higher replicative fitness than did the 17E or the 64M polymorphism in the CFR02_AG clone. These findings suggest that subtype-specific, linked polymorphisms can result in hypersusceptibility to ARVs. Considering the potential benefit of HS to treatment outcome, screening for potential HS-linked polymorphisms as well as preexisting drug resistance mutations in treatment-naïve patients may guide the choice of ARVs for the best treatment outcome.
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Frederika, Edith, Irine Normalina, Nasronudin Nasronudin e Rury Mega. "EVALUATION ON THE EFFECT OF ANTIRETROVIRAL DRUGS ON CD4 T-CELL AND THE INCREMENT OF BODY WEIGHT AMONG HIV-AIDS PATIENTS IN SURABAYA". Indonesian Journal of Tropical and Infectious Disease 3, n.º 2 (20 de junho de 2016): 92. http://dx.doi.org/10.20473/ijtid.v3i2.210.
Texto completo da fonteResumo:
Antiretroviral drug discovery has encouraged a revolution in the care of people living with HIV, although it has not been able to cure diseases and to increase the challenge in terms of drug side effects. Side effects of antiretroviral drugs are fairly common occurrences in HIV patients and generally occurr within the first three months after initiation of antiretroviral therapy, although long-term side effects are also often found afterwards. This study aims to evaluate the number of CD4 T-cells in patients with AIDS before and after getting on ARV therapy, the side effects arising during the taking of ARVs are related to the increment of body weight among the HIVAIDS patients. Subjects were then narrowed down from 25 to 12 due to the incomplete data. The results showed that the top three most side effects which often occur in people with AIDS are appetite loss (20.0%), nausea (17.8%), and diarrhoea (15.6%). Meanwhile, about 58% of the subjects experienced increment of their body weight, and 42% were losing weight due to the side effects of the ARV therapy. Among those who lost their body weight, 50% were in the productive ages between 21–30 years old. The present study shows that combination antiretroviral therapy gives good results to the increased number of CD4 T-cells in patients living with HIV, as shown by the tendency of an increment in the number of CD4 T-cells in patients who received antiretroviral therapy. However, around 42% of those patients were losing weight because of the side effects of the therapy. Therefore, the importance of giving specific nutrient to overcome with the weight loss is needed to be given to the patients HIV instead of only giving the ARV treatment.
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Courlet, Perrine, Monia Guidi, Susana Alves Saldanha, Matthias Cavassini, Marcel Stoeckle, Thierry Buclin, Catia Marzolini, Laurent A. Decosterd e Chantal Csajka. "Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs". European Journal of Clinical Pharmacology 77, n.º 7 (16 de janeiro de 2021): 979–87. http://dx.doi.org/10.1007/s00228-020-03060-2.
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Abstract Purpose Drug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations. Methods A population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs. Results Amlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%. Conclusion Coadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.
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Hassen, Aregash, e Yasmin Mohammed. "Antiretroviral Therapy Adherence Level and Associated Factors Among HIV/AIDS Patients in Jimma Zone Government Health Facilities, ART Clinics, South-west Ethiopia". International Journal of Multicultural and Multireligious Understanding 5, n.º 5 (14 de janeiro de 2019): 331. http://dx.doi.org/10.18415/ijmmu.v5i5.535.
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Optimal and strict adherence to Antiretroviral Viral Therapy a need for over the long period to achieve the goals of ART and obtain maximum benefits of ART. However, PLWHA find it very difficult to take ARVs drug as precisely as they should for a number of reasons. Therefore, this study aimed at examining the level of antiretroviral therapy adherence and identifying possible associated factors for ART adherence behavior in Jimma zone government ART facilities. A facility based cross-sectional study was conducted in the ART clinics of Jimma zone governmental health facilities in which ARV treatment supplied from November 25/2015 – February 30/2016 for a period of 4 months. 352 adult PLWHA (190 female and 162 male) ranged in age from 15-62 years (Mean=37.1, SD= 8.95), with 100% response rate, were our study participants. Binary logistic regression was used to perform bivariate and multivariate analyses to determine the association between study variables and ART adherence status. 259(73.6%) participants were adherent (>=95%) and 93(26.4%) were non-adherent (<95%) to the prescribed dose of ARV drugs over the past seven days prior to the interview. The main reasons for skipping the prescribed ARV drugs were, busyness (78.5%), having too many pills (71%), felt depressed (68.8%), taking the drugs reminded HIV infected (66.7%), did not want other see (62.4%), and felt asleep(60.2%). The last stepwise regression analysis revealed that, educational status, knowledge of HIV/AIDS, use of additional drugs and access to reliable pharmacy were significantly associated with ART adherence status. So, efforts to maximize ART adherence should focus on addressing these associated significant factors.
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Weber, Jan, Ana C. Vazquez, Dane Winner, Justine D. Rose, Doug Wylie, Ariel M. Rhea, Kenneth Henry et al. "Novel Method for Simultaneous Quantification of Phenotypic Resistance to Maturation, Protease, Reverse Transcriptase, and Integrase HIV Inhibitors Based on 3′Gag(p2/p7/p1/p6)/PR/RT/INT-Recombinant Viruses: a Useful Tool in the Multitarget Era of Antiretroviral Therapy". Antimicrobial Agents and Chemotherapy 55, n.º 8 (31 de maio de 2011): 3729–42. http://dx.doi.org/10.1128/aac.00396-11.
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ABSTRACTTwenty-six antiretroviral drugs (ARVs), targeting five different steps in the life cycle of the human immunodeficiency virus type 1 (HIV-1), have been approved for the treatment of HIV-1 infection. Accordingly, HIV-1 phenotypic assays based on common cloning technology currently employ three, or possibly four, different recombinant viruses. Here, we describe a system to assess HIV-1 resistance to all drugs targeting the three viral enzymes as well as viral assembly using a single patient-derived, chimeric virus. Patient-derived p2-INT (gag-p2/NCp7/p1/p6/pol-PR/RT/IN) products were PCR amplified as a single fragment (3,428 bp) or two overlapping fragments (1,657 bp and 2,002 bp) and then recombined into a vector containing a near-full-length HIV-1 genome with theSaccharomyces cerevisiaeuracil biosynthesis gene (URA3) replacing the 3,428 bp p2-INT segment (Dudley et al., Biotechniques 46:458–467, 2009). P2-INT-recombinant viruses were employed in drug susceptibility assays to test the activity of protease (PI), nucleoside/nucleotide reverse transcriptase (NRTI), nonnucleoside reverse transcriptase (NNRTI), and integrase strand-transfer (INSTI) inhibitors. Using a single standardized test (ViralARTS HIV), this new technology permits the rapid and automated quantification of phenotypic resistance for all known and candidate antiretroviral drugs targeting all viral enzymes (PR, RT, including polymerase and RNase H activities, and IN), some of the current and potential assembly inhibitors, and any drug targeting Pol or Gag precursor cleavage sites (relevant for PI and maturation inhibitors) This novel assay may be instrumental (i) in the development and clinical assessment of novel ARV drugs and (ii) to monitor patients failing prior complex treatment regimens.
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Kodidela, Sunitha, Namita Sinha, Asit Kumar e Santosh Kumar. "Anti-HIV Activity of Cucurbitacin-D against Cigarette Smoke Condensate-Induced HIV Replication in the U1 Macrophages". Viruses 13, n.º 6 (27 de maio de 2021): 1004. http://dx.doi.org/10.3390/v13061004.
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Chemodietary agents are emerging as promising adjuvant therapies in treating various disease conditions. However, there are no adjuvant therapies available to minimize the neurotoxicity of currently existing antiretroviral drugs (ARVs). In this study, we investigated the anti-HIV effect of a chemodietary agent, Cucurbitacin-D (Cur-D), in HIV-infected macrophages using an in-vitro blood–brain barrier (BBB) model. Since tobacco smoking is prevalent in the HIV population, and it exacerbates HIV replication, we also tested the effect of Cur-D against cigarette smoke condensate (CSC)-induced HIV replication. Our results showed that Cur-D treatment reduces the viral load in a dose-dependent (0–1 μM) manner without causing significant toxicity at <1 μM concentration. Further, a daily dose of Cur-D (0.1 μM) not only reduced p24 in control conditions, but also reduced CSC (10 μg/mL)-induced p24 in U1 cells. Similarly, Cur-D (single dose of 0.4 μM) significantly reduced the CSC (single dose of 40 μg/mL)-induced HIV replication across the BBB model. In addition, treatment with Cur-D reduced the level of pro-inflammatory cytokine IL-1β. Therefore, Cur-D, as an adjuvant therapy, may be used not only to suppress HIV in the brain, but also to reduce the CNS toxicity of currently existing ARVs.
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Lavender, Kerry J., Kathrin Gibbert, Karin E. Peterson, Erik Van Dis, Sandra Francois, Tyson Woods, Ronald J. Messer et al. "Interferon Alpha Subtype-Specific Suppression of HIV-1 InfectionIn Vivo". Journal of Virology 90, n.º 13 (20 de abril de 2016): 6001–13. http://dx.doi.org/10.1128/jvi.00451-16.
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ABSTRACTAlthough all 12 subtypes of human interferon alpha (IFN-α) bind the same receptor, recent results have demonstrated that they elicit unique host responses and display distinct efficacies in the control of different viral infections. The IFN-α2 subtype is currently in HIV-1 clinical trials, but it has not consistently reduced viral loads in HIV-1 patients and is not the most effective subtype against HIV-1in vitro. We now demonstrate in humanized mice that, when delivered at the same high clinical dose, the human IFN-α14 subtype has very potent anti-HIV-1 activity whereas IFN-α2 does not. In both postexposure prophylaxis and treatment of acute infections, IFN-α14, but not IFN-α2, significantly suppressed HIV-1 replication and proviral loads. Furthermore, HIV-1-induced immune hyperactivation, which is a prognosticator of disease progression, was reduced by IFN-α14 but not IFN-α2. Whereas ineffective IFN-α2 therapy was associated with CD8+T cell activation, successful IFN-α14 therapy was associated with increased intrinsic and innate immunity, including significantly higher induction of tetherin and MX2, increased APOBEC3G signature mutations in HIV-1 proviral DNA, and higher frequencies of TRAIL+NK cells. These results identify IFN-α14 as a potent new therapeutic that operates via mechanisms distinct from those of antiretroviral drugs. The ability of IFN-α14 to reduce both viremia and proviral loadsin vivosuggests that it has strong potential as a component of a cure strategy for HIV-1 infections. The broad implication of these results is that the antiviral efficacy of each individual IFN-α subtype should be evaluated against the specific virus being treated.IMPORTANCEThe naturally occurring antiviral protein IFN-α2 is used to treat hepatitis viruses but has proven rather ineffective against HIV in comparison to triple therapy with the antiretroviral (ARV) drugs. Although ARVs suppress the replication of HIV, they fail to completely clear infections. Since IFN-α acts by different mechanism than ARVs and has been shown to reduce HIV proviral loads, clinical trials are under way to test whether IFN-α2 combined with ARVs might eradicate HIV-1 infections. IFN-α is actually a family of 12 distinct proteins, and each IFN-α subtype has different efficacies toward different viruses. Here, we use mice that contain a human immune system, so they can be infected with HIV. With this model, we demonstrate that while IFN-α2 is only weakly effective against HIV, IFN-α14 is extremely potent. This discovery identifies IFN-α14 as a more powerful IFN-α subtype for use in combination therapy trials aimed toward an HIV cure.
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Patel, M., P. Bessong e H. Liu. "Traditional Medicines, HIV, and Related Infections". Advances in Dental Research 23, n.º 1 (25 de março de 2011): 159–64. http://dx.doi.org/10.1177/0022034511400077.
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Traditional medicines are an integral part of health care worldwide, even though their efficacy has not been scientifically proven. HIV-infected individuals may use them singularly or in combination with conventional medicines. Many in vitro studies have proven the anti-HIV, anti- Candida, and anti–herpes simplex virus potential of traditional plants and identified some of the mechanisms of action. Very few in vivo studies are available that involve a small number of participants and show controversial results. In addition, knowledge is limited of the role of traditional medicines in the enhancement of the immune system. The use of traditional medicines with antiretroviral drugs (ARVs) has created a problem because drug interactions compromise the efficacy of ARVs. Several currently popular plants have been studied in the laboratory for their interaction with ARVs, with disadvantageous results. Unfortunately, no clinical trials are available. The science of traditional medicines is relatively new and is at present being modernized worldwide. However, there are still ethical issues regarding traditional medicines that need to be addressed—for example, regulations regarding quality control and standardization of medicines, regulation and education of healers who deliver these medicines, and unregulated clinical trials. The workshop addressed the following questions about traditional medicine and their use in HIV infection: What are the mechanisms of action of anti-HIV traditional medicines? Should traditional medicines be used in conjunction with ARV? Do traditional medicines enhance the immune system? Should medicinal plants be used for the control of oral infections associated with HIV? What are the ethical issues surrounding the use of traditional medicines for the treatment of HIV and associated infections?
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Mel’nikov, Arkadiy Sergeevich, Elena Alekseevna Rukoyatkina, Roman Azizovich Funden e Inga Borisovna Latysheva. "Women and HIV infection, current status of the problem". Pediatrician (St. Petersburg) 6, n.º 1 (15 de março de 2015): 5–10. http://dx.doi.org/10.17816/ped615-10.
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The increase in the number of people infected with the human immunodeficiency virus (HIV) and increasing the share of women among them, as well as annual growth in the number of births to HIV-infected women define extraordinary relevance for the prevention of HIV transmission from mother to child. Tactics to prevent HIV transmission from mother to child is determined by a set of epidemiological, clinical and laboratory parameters and selected for each individual woman after consultation with the appropriate professionals. It is shown that the most important factor affecting the likelihood of HIV transmission from mother to fetus and child, is the concentration of virus in the blood of women (the so-called viral load - VL) during pregnancy and childbirth, so it is important to achieve it undetectable levels as early as possible in pregnancy. As the activities carried out in the framework of this prevention, the importance of timely diagnosis of HIV infection and identifying high risk of HIV infection in pregnant women, chemoprophylaxis (CP) carried out with the help of antiretroviral drugs (ARVs), woman and child, the tactics of pregnancy and childbirth, and also keeping the child in the first half year of life, including avoidance of breastfeeding. Appointment ARV HIV-infected women may be necessary not only to prevent infection of the child, but also to treat the woman. In appointing ART necessary to minimize potential adverse effects of ARV drugs on the fetus, which is especially important in the I trimester of pregnancy. Therefore, the starting date of receiving ARVs in pregnant should be optimal from the point of view of the effectiveness of the treatment of women, the effectiveness of prophylaxis of infection of the child and the safety of the fetus.
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Mokheseng, Mamolise, Gideon S. Horn e Aileen G. Klopper. "Supply chain solutions to improve the distribution of antiretroviral drugs (ARVs) to clinics in rural areas: A case study of the QwaQwa district". Health SA Gesondheid 22 (dezembro de 2017): 93–104. http://dx.doi.org/10.1016/j.hsag.2016.11.001.
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Navarro, Rafaella, Jose Luis Paredes, Juan Echevarria, Elsa González-Lagos, Ana Graña, Fernando Mejía e Larissa Otero. "HIV and antiretroviral treatment knowledge gaps and psychosocial burden among persons living with HIV in Lima, Peru". PLOS ONE 16, n.º 8 (19 de agosto de 2021): e0256289. http://dx.doi.org/10.1371/journal.pone.0256289.
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This study aims to describe knowledge on HIV and antiretroviral (ARV) treatment and psychosocial factors among people living with HIV (PLWH) in Lima, Perú, to explore characteristics associated to this knowledge, and determine its impact on sustained viral suppression. A cross-sectional survey was conducted among 171 PLWH at the largest referral health care center in Lima. The psychosocial factors measured were depression, risk of alcoholism, use of illegal drugs and disclosure. A participant had “poor knowledge” when less than 80% of replies were correct. Sustained viral suppression was defined as two consecutive viral loads under 50 copies/mL. A total of 49% and 43% had poor HIV and ARV knowledge respectively; 48% of the study population screened positive for depression and 27% reported feeling unsupported by the person they disclosed to. The largest gaps in HIV and ARV knowledge were among 98 (57%) that did not recognize that HIV increased the risk of cancer and among 57 (33%) participants that did not disagree with the statement that taking a double dose of ARV if they missed one. Moderate depression was significantly associated to poor HIV and ARV knowledge. Non-disclosure and being on ARVs for less than 6 months were associated with not achieving sustained viral suppression. Our findings highlight important HIV and ARV knowledge gaps of PLWH and a high burden of psychosocial problems, especially of depression, among PLWH in Lima, Peru. Increasing knowledge and addressing depression and disclosure could improve care of PLWH.
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Shahriar, Rajin, Soo-Yon Rhee, Tommy F. Liu, W. Jeffrey Fessel, Anthony Scarsella, William Towner, Susan P. Holmes, Andrew R. Zolopa e Robert W. Shafer. "Nonpolymorphic Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Treatment-Selected Mutations". Antimicrobial Agents and Chemotherapy 53, n.º 11 (31 de agosto de 2009): 4869–78. http://dx.doi.org/10.1128/aac.00592-09.
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ABSTRACT The spectrum of human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT) mutations selected by antiretroviral (ARV) drugs requires ongoing reassessment as ARV treatment patterns evolve and increasing numbers of protease and RT sequences of different viral subtypes are published. Accordingly, we compared the prevalences of protease and RT mutations in HIV-1 group M sequences from individuals with and without a history of previous treatment with protease inhibitors (PIs) or RT inhibitors (RTIs). Mutations in protease sequences from 26,888 individuals and in RT sequences from 25,695 individuals were classified according to whether they were nonpolymorphic in untreated individuals and whether their prevalence increased fivefold with ARV therapy. This analysis showed that 88 PI-selected and 122 RTI-selected nonpolymorphic mutations had a prevalence that was fivefold higher in individuals receiving ARVs than in ARV-naïve individuals. This was an increase of 47% and 77%, respectively, compared with the 60 PI- and 69 RTI-selected mutations identified in a similar analysis that we published in 2005 using subtype B sequences obtained from one-fourth as many individuals. In conclusion, many nonpolymorphic mutations in protease and RT are under ARV selection pressure. The spectrum of treatment-selected mutations is changing as data for more individuals are collected, treatment exposures change, and the number of available sequences from non-subtype B viruses increases.
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Lang, Raynell, Hartmut B. Krentz, Quang Vu e M. John Gill. "2505. Incidence of Transmitted Drug Resistance and Its Clinical Implications Between 1999 and 2018 in a Regional HIV Population". Open Forum Infectious Diseases 6, Supplement_2 (outubro de 2019): S868—S869. http://dx.doi.org/10.1093/ofid/ofz360.2183.
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Abstract Background Baseline genotype antiretroviral resistance testing (GART) were introduced to allow better selection of antiretroviral therapy (ART), minimizing the use of less effective drugs and risk for ongoing transmission of drug-resistant virus. However, the value of baseline GART has recently been questioned due to declining incidence of TDR in the setting of improved drug tolerability profiles and effectiveness. We aimed to evaluate the long-term clinical and economic impact of TDR using a well characterized, geographically defined cohort between 1999–2018. Methods In the Southern Alberta Cohort (SAC) database we identified all (ART naïve) HIV patients, ≥16 years of age, with a baseline GART. They were classified by presence or absence of TDR. Clinical and sociodemographic data were obtained from database and chart review. All statistical analysis was performed with Stata. Results During the study 745 GART tests were done on ART naïve patients. Baseline ART resistance was documented in 78 /745 patients. TDR was to the NNRTI class in 59 (75.6%), to NRTI in 12 (15.4%) and to the PI class in 7 (8.9%) patients. Two patients had two class resistance and none had INSTI resistance. There was a significant difference in cost per year of therapy comparing the TDR and control ($17,152/year vs. $15,362/year, P ≤ 0.001). Patients with TDR had greater pill burden with 20% being on BID/TID ART regimens compared with the controls of 13% (P = 0.003). No differences in incident ART adverse events (12.8% TDR vs. 13.3% no TDR), drug interactions (1.6% vs. 1.0%) or reasons to stop or change ARVs were seen between study groups. The duration of ART on any given drug class was similar between the two populations (P = 0.6694) as was status of viral suppression at one year 73% vs. 65%. Conclusion Presence of TDR at baseline had little immediate impact on ART initiation or tolerance, but by limiting choices negatively impacted pill burden and dosing as well as drug costs. Disclosures All authors: No reported disclosures.
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Bunglawala, Fazila, Rajith K. R. Rajoli, Mark Mirochnick, Andrew Owen e Marco Siccardi. "Prediction of dolutegravir pharmacokinetics and dose optimization in neonates via physiologically based pharmacokinetic (PBPK) modelling". Journal of Antimicrobial Chemotherapy 75, n.º 3 (20 de dezembro de 2019): 640–47. http://dx.doi.org/10.1093/jac/dkz506.
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Abstract Background Only a few antiretroviral drugs (ARVs) are recommended for use during the neonatal period and there is a need for more to be approved to increase treatment and prophylaxis strategies. Dolutegravir, a selective integrase inhibitor, has potential for treatment of HIV infection and prophylaxis of transmission in neonates. Objectives To model the pharmacokinetics of dolutegravir in neonates and to simulate a theoretical optimal dosing regimen. Methods The physiologically based pharmacokinetic (PBPK) model was built incorporating the age-related changes observed in neonates. Virtual neonates between 0 and 28 days were simulated. The model was validated against observed clinical data for raltegravir and midazolam in neonates, prior to the prediction of dolutegravir pharmacokinetics. Results Both raltegravir and midazolam passed the criteria for model qualification, with simulated data within 1.8-fold of clinical data. The qualified model predicted the pharmacokinetics for several multidose regimens of dolutegravir. Regimen 6 involved 5 mg doses with a 48 h interval from Day 1–20, increasing to 5 mg once daily on Week 3, yielding AUC and Ctrough values of 37.2 mg·h/L and 1.3 mg/L, respectively. These exposures are consistent with those observed in paediatric patients receiving dolutegravir. Conclusions Dolutegravir pharmacokinetics were successfully simulated in the neonatal PBPK model. The predictions suggest that during the first 3 weeks of life a 5 mg dose administered every 48 h may achieve plasma exposures needed for therapy and prophylaxis.
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Dewi, Nurina Dewi Ayu, e Ira Nurmala. "DUKUNGAN SOSIAL TERHADAP KONSUMSI ARV IBU RUMAH TANGGA PENDERITA HIV DI SURABAYA". Jurnal PROMKES 4, n.º 2 (26 de fevereiro de 2018): 165. http://dx.doi.org/10.20473/jpk.v4.i2.2016.165-176.
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In 2014, East Java ranks second highest HIV cases in Indonesia to 32.872 the number of HIV cases. Concern HIV disease is exposed when in 2014 based on the sequence of work housewife ranks second HIV cases in Surabaya with the number of 129 cases. The case of a housewife who has HIV is higher compared to commercial sex workers. Therapeutic treatment for patients with HIV using antiretroviral drugs. ARV consumption serves to suppress the growth of HIV. This study was conducted to determine the social support for the consumptionof ARV housewife in Surabaya. The research is a qualitative research with case study approach. Informants used are numbered 9 consisting of three housewives with HIV, three families and three close friends housewife with HIV. The study was conducted from May to December 2016. Data collection using an interview guide and study documents. The results showed that there is social support for the consumption of housewives with HIV. Their diff erences in background,control beliefs, perceived behavioral control, intention-owned and social support received informants could aff ect the consumption of ARVs do informant. The conclusion that can be drawn is that the most infl uential social support for the consumption of ARV housewife with HIV in Surabaya is emotional support and support networks. Another eff ect of ARV consumption comes from a background that was once owned by housewives with HIV.Keywords: social support, consumption of ARV, housewife, HI