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  1. Vagenas P, Azar MM, Copenhaver MM, Springer SA, Molina PE, Altice FL
    Curr HIV/AIDS Rep, 2015 Dec;12(4):421-36.
    PMID: 26412084 DOI: 10.1007/s11904-015-0285-5
    Alcohol use is highly prevalent globally with numerous negative consequences to human health, including HIV progression, in people living with HIV (PLH). The HIV continuum of care, or treatment cascade, represents a sequence of targets for intervention that can result in viral suppression, which ultimately benefits individuals and society. The extent to which alcohol impacts each step in the cascade, however, has not been systematically examined. International targets for HIV treatment as prevention aim for 90 % of PLH to be diagnosed, 90 % of them to be prescribed with antiretroviral therapy (ART), and 90 % to achieve viral suppression; currently, only 20 % of PLH are virally suppressed. This systematic review, from 2010 through May 2015, found 53 clinical research papers examining the impact of alcohol use on each step of the HIV treatment cascade. These studies were mostly cross-sectional or cohort studies and from all income settings. Most (77 %) found a negative association between alcohol consumption on one or more stages of the treatment cascade. Lack of consistency in measurement, however, reduced the ability to draw consistent conclusions. Nonetheless, the strong negative correlations suggest that problematic alcohol consumption should be targeted, preferably using evidence-based behavioral and pharmacological interventions, to indirectly increase the proportion of PLH achieving viral suppression, to achieve treatment as prevention mandates, and to reduce HIV transmission.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  2. Loeliger KB, Meyer JP, Desai MM, Ciarleglio MM, Gallagher C, Altice FL
    PLoS Med, 2018 10;15(10):e1002667.
    PMID: 30300351 DOI: 10.1371/journal.pmed.1002667
    BACKGROUND: Sustained retention in HIV care (RIC) and viral suppression (VS) are central to US national HIV prevention strategies, but have not been comprehensively assessed in criminal justice (CJ) populations with known health disparities. The purpose of this study is to identify predictors of RIC and VS following release from prison or jail.

    METHODS AND FINDINGS: This is a retrospective cohort study of all adult people living with HIV (PLWH) incarcerated in Connecticut, US, during the period January 1, 2007, to December 31, 2011, and observed through December 31, 2014 (n = 1,094). Most cohort participants were unmarried (83.7%) men (77.0%) who were black or Hispanic (78.1%) and acquired HIV from injection drug use (72.6%). Prison-based pharmacy and custody databases were linked with community HIV surveillance monitoring and case management databases. Post-release RIC declined steadily over 3 years of follow-up (67.2% retained for year 1, 51.3% retained for years 1-2, and 42.5% retained for years 1-3). Compared with individuals who were not re-incarcerated, individuals who were re-incarcerated were more likely to meet RIC criteria (48% versus 34%; p < 0.001) but less likely to have VS (72% versus 81%; p = 0.048). Using multivariable logistic regression models (individual-level analysis for 1,001 individuals after excluding 93 deaths), both sustained RIC and VS at 3 years post-release were independently associated with older age (RIC: adjusted odds ratio [AOR] = 1.61, 95% CI = 1.22-2.12; VS: AOR = 1.37, 95% CI = 1.06-1.78), having health insurance (RIC: AOR = 2.15, 95% CI = 1.60-2.89; VS: AOR = 2.01, 95% CI = 1.53-2.64), and receiving an increased number of transitional case management visits. The same factors were significant when we assessed RIC and VS outcomes in each 6-month period using generalized estimating equations (for 1,094 individuals contributing 6,227 6-month periods prior to death or censoring). Additionally, receipt of antiretroviral therapy during incarceration (RIC: AOR = 1.33, 95% CI 1.07-1.65; VS: AOR = 1.91, 95% CI = 1.56-2.34), early linkage to care post-release (RIC: AOR = 2.64, 95% CI = 2.03-3.43; VS: AOR = 1.79; 95% CI = 1.45-2.21), and absolute time and proportion of follow-up time spent re-incarcerated were highly correlated with better treatment outcomes. Limited data were available on changes over time in injection drug use or other substance use disorders, psychiatric disorders, or housing status.

    CONCLUSIONS: In a large cohort of CJ-involved PLWH with a 3-year post-release evaluation, RIC diminished significantly over time, but was associated with HIV care during incarceration, health insurance, case management services, and early linkage to care post-release. While re-incarceration and conditional release provide opportunities to engage in care, reducing recidivism and supporting community-based RIC efforts are key to improving longitudinal treatment outcomes among CJ-involved PLWH.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  3. Rich KM, Wickersham JA, Valencia Huamaní J, Kiani SN, Cabello R, Elish P, et al.
    LGBT Health, 2018;5(8):477-483.
    PMID: 30874476 DOI: 10.1089/lgbt.2017.0186
    PURPOSE: Globally, transgender women (TGW) experience a high burden of adverse health outcomes, including a high prevalence of HIV and sexually transmitted infections (STIs) as well as psychiatric disorders and substance use disorders. To address gaps in HIV research in Peru focused specifically on TGW, this study presents characteristics of a sample of HIV-positive TGW and identifies factors associated with viral suppression.

    METHODS: Between June 2015 and August 2016, 50 HIV-positive TGW were recruited in Lima, Peru. Multivariable logistic regression was used to identify factors associated with viral suppression (<200 copies/mL) among the TGW.

    RESULTS: Among TGW, 85% achieved viral suppression. Approximately half (54%) reported anal sex with more than five partners in the past 6 months, 38% reported sex work, 68% had not disclosed their HIV status to one or more of their partners, and 38% reported condomless sex with their last partner. The prevalence of alcohol use disorders was high (54%), and 38% reported use of drugs in the past year. Moderate-to-severe drug use significantly reduced odds of achieving viral suppression (adjusted odds ratio 0.69; 95% confidence interval: 0.48-0.98).

    CONCLUSION: Our findings highlight the need for integrated treatment for substance disorders in HIV care to increase the viral suppression rate among TGW in Lima, Peru.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  4. Lim SH, Mburu G, Bourne A, Pang J, Wickersham JA, Wei CKT, et al.
    PLoS One, 2017;12(9):e0182838.
    PMID: 28902857 DOI: 10.1371/journal.pone.0182838
    OBJECTIVE: We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia.

    METHODS: An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP.

    RESULTS: Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals.

    CONCLUSIONS: Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  5. Balasubramaniam K
    Issues Med Ethics, 2000 Jan-Mar;8(1):26-7.
    PMID: 16323335
    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  6. Bekker LG, Alleyne G, Baral S, Cepeda J, Daskalakis D, Dowdy D, et al.
    Lancet, 2018 Jul 28;392(10144):312-358.
    PMID: 30032975 DOI: 10.1016/S0140-6736(18)31070-5
    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  7. Ismail I, Bulgiba A
    Prev Med, 2013;57 Suppl:S27-30.
    PMID: 23295172 DOI: 10.1016/j.ypmed.2012.12.023
    To determine predictors of unsuccessful treatment in HIV-infected tuberculosis (TB) patients.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  8. Kharkwal H, Kumar BK, Murugesan S, Singhvi G, Avasthi P, Goyal A, et al.
    Future Med Chem, 2021 02;13(3):269-286.
    PMID: 33399497 DOI: 10.4155/fmc-2020-0257
    Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  9. Yap PK, Loo Xin GL, Tan YY, Chellian J, Gupta G, Liew YK, et al.
    J Pharm Pharmacol, 2019 Sep;71(9):1339-1352.
    PMID: 31144296 DOI: 10.1111/jphp.13107
    OBJECTIVES: Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP.

    KEY FINDINGS: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class.

    SUMMARY: Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  10. Qin Y, Huang X, Chen H, Liu X, Li Y, Hou J, et al.
    BMC Infect Dis, 2020 Jul 29;20(1):551.
    PMID: 32727383 DOI: 10.1186/s12879-020-05260-8
    BACKGROUND: Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia.

    METHODS: In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity.

    RESULTS: 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58-16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA.

    CONCLUSIONS: The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  11. Jung IY, Boettiger D, Wong WW, Lee MP, Kiertiburanakul S, Chaiwarith R, et al.
    J Int AIDS Soc, 2017 12;20(4).
    PMID: 29243388 DOI: 10.1002/jia2.25016
    INTRODUCTION: Although substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV-infected patients in non-clinical trial settings in Asian countries.

    METHODS: The study population consisted of HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within-class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.

    RESULTS: Of 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.

    CONCLUSIONS: The rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non-clinical trial settings in Asian countries.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  12. De Clercq E
    Med Res Rev, 2000 Sep;20(5):323-49.
    PMID: 10934347
    A large variety of natural products have been described as anti-HIV agents, and for a portion thereof the target of interaction has been identified. Cyanovirin-N, a 11-kDa protein from Cyanobacterium (blue-green alga) irreversibly inactivates HIV and also aborts cell-to-cell fusion and transmission of HIV, due to its high-affinity interaction with gp120. Various sulfated polysaccharides extracted from seaweeds (i.e., Nothogenia fastigiata, Aghardhiella tenera) inhibit the virus adsorption process. Ingenol derivatives may inhibit virus adsorption at least in part through down-regulation of CD4 molecules on the host cells. Inhibition of virus adsorption by flavanoids such as (-)epicatechin and its 3-O-gallate has been attributed to an irreversible interaction with gp120 (although these compounds are also known as reverse transcriptase inhibitors). For the triterpene glycyrrhizin (extracted from the licorice root Glycyrrhiza radix) the mode of anti-HIV action may at least in part be attributed to interference with virus-cell binding. The mannose-specific plant lectins from Galanthus, Hippeastrum, Narcissus, Epipac tis helleborine, and Listera ovata, and the N-acetylgl ucosamine-specific lectin from Urtica dioica would primarily be targeted at the virus-cell fusion process. Various other natural products seem to qualify as HIV-cell fusion inhibitors: the siamycins [siamycin I (BMY-29304), siamycin II (RP 71955, BMY 29303), and NP-06 (FR901724)] which are tricyclic 21-amino-acid peptides isolated from Streptomyces spp that differ from one another only at position 4 or 17 (valine or isoleucine in each case); the betulinic acid derivative RPR 103611, and the peptides tachyplesin and polyphemusin which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus, i.e., the 18-amino-acid peptide T22 from which T134 has been derived. Both T22 and T134 have been shown to block T-tropic X4 HIV-1 strains through a specific antagonism with the HIV corecept or CXCR4. A number of natural products have been reported to interact with the reverse transcriptase, i.e., baicalin, avarol, avarone, psychotrine, phloroglucinol derivatives, and, in particular, calanolides (from the tropical rainforest tree, Calophyllum lanigerum) and inophyllums (from the Malaysian tree, Calophyllum inophyllum). The natural marine substance illimaquinone would be targeted at the RNase H function of the reverse transcriptase. Curcumin (diferuloylmethane, from turmeric, the roots/rhizomes of Curcuma spp), dicaffeoylquinic and dicaffeoylt artaric acids, L-chicoric acid, and a number of fungal metabolites (equisetin, phomasetin, oteromycin, and integric acid) have all been proposed as HIV-1 integrase inhibitors. Yet, we have recently shown that L-c hicoric acid owes its anti-HIV activity to a specific interaction with the viral envelope gp120 rather than integrase. A number of compounds would be able to inhibit HIV-1 gene expression at the transcription level: the flavonoid chrysin (through inhibition of casein kinase II, the antibacter ial peptides melittin (from bee venom) and cecropin, and EM2487, a novel substance produced by Streptomyces. (ABSTRACT TRUNCATED)
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  13. Purcell DF, Elliott JH, Ross AL, Frater J
    Retrovirology, 2013 Nov 13;10:134.
    PMID: 24224983 DOI: 10.1186/1742-4690-10-134
    The International AIDS Society convened the multi-stakeholder "Towards an HIV Cure" symposium in Kuala Lumpur, Malaysia in 2013 to address the significant research challenges posed by the search for a cure for HIV infection. Current antiretroviral regimens select for a small reservoir of cells that harbour latent HIV provirus, produce few or no HIV virions, and resist detection or clearance by host immunity. The symposium examined basic molecular science and animal model data, and emerging and ongoing clinical trial results to prioritise strategies and determine the viral and immune responses that could lead to HIV remission without ART. Here we review the presentations that scrutinized the molecular mechanisms controlling virus expression from proviral DNA, and the intrinsic cellular restriction and immune mechanisms preventing viral production. Insights from the basic science have translated into new therapeutic strategies seeking HIV remission without ongoing therapy, and much interest was focused on these ongoing trials. We also summarise the emerging ethical issues and patient expectations as concepts move into the clinic.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  14. Tan HY, Yong YK, Andrade BB, Shankar EM, Ponnampalavanar S, Omar SF, et al.
    AIDS, 2015 Feb 20;29(4):421-31.
    PMID: 25565499 DOI: 10.1097/QAD.0000000000000557
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a substantial problem in HIV/TB coinfected patients commencing antiretroviral therapy (ART). The immunopathogenesis of TB-IRIS includes increased production of proinflammatory chemokines and cytokines, including interleukin-18, which is a signature cytokine of the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 inflammasome. We compared plasma levels of interleukin-18 and other biomarkers of monocyte/macrophage activation in the prediction and characterization of TB-IRIS.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  15. Lim A, Tan D, Price P, Kamarulzaman A, Tan HY, James I, et al.
    AIDS, 2007 Jul 31;21(12):1525-34.
    PMID: 17630546
    To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR).
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  16. del Amo J, Moreno S, Bucher HC, Furrer H, Logan R, Sterne J, et al.
    Clin Infect Dis, 2012 May;54(9):1364-72.
    PMID: 22460971 DOI: 10.1093/cid/cis203
    BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

    METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.

    RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.

    CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  17. Bijker R, Jiamsakul A, Kityo C, Kiertiburanakul S, Siwale M, Phanuphak P, et al.
    J Int AIDS Soc, 2017 03 03;20(1):21218.
    PMID: 28362063 DOI: 10.7448/IAS.20.1.21218
    INTRODUCTION: Our understanding of how to achieve optimal long-term adherence to antiretroviral therapy (ART) in settings where the burden of HIV disease is highest remains limited. We compared levels and determinants of adherence over time between HIV-positive persons receiving ART who were enrolled in a bi-regional cohort in sub-Saharan Africa and Asia.
    METHODS: This multicentre prospective study of adults starting first-line ART assessed patient-reported adherence at follow-up clinic visits using a 30-day visual analogue scale. Determinants of suboptimal adherence (<95%) were assessed for six-month intervals, using generalized estimating equations multivariable logistic regression with multiple imputations. Region of residence (Africa vs. Asia) was assessed as a potential effect modifier.
    RESULTS: Of 13,001 adherence assessments in 3934 participants during the first 24 months of ART, 6.4% (837) were suboptimal, with 7.3% (619/8484) in the African cohort versus 4.8% (218/4517) in the Asian cohort (p 
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  18. Hanna L
    BETA, 1999 Apr;12(2):8-9.
    PMID: 11366704
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  19. Mustafa S, Yusuf WN, Woillard JB, Choon TS, Hassan NB
    Eur J Clin Pharmacol, 2016 Jul;72(7):831-8.
    PMID: 27025609 DOI: 10.1007/s00228-016-2049-6
    AIMS: Nevirapine is the first non-nucleoside reverse-transcriptase inhibitor approved and is widely used in combination therapy to treat HIV-1 infection. The pharmacokinetics of nevirapine was extensively studied in various populations with a parametric approach. Hence, this study was aimed to determine population pharmacokinetic parameters in Malaysian HIV-infected patients with a non-parametric approach which allows detection of outliers or non-normal distribution contrary to the parametric approach.

    METHODS: Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters' estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC.

    RESULTS: The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC.

    CONCLUSIONS: In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  20. HIV-CAUSAL Collaboration, Cain LE, Phillips A, Olson A, Sabin C, Jose S, et al.
    Clin Infect Dis, 2015 Apr 15;60(8):1262-8.
    PMID: 25567330 DOI: 10.1093/cid/ciu1167
    BACKGROUND: Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience.

    METHODS: We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes.

    RESULTS: A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone.

    CONCLUSIONS: Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
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