Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Bio-analytical Assay Methods used in Therapeutic Drug Monitoring of Antiretroviral Drugs-A Review

Background: Several clinical trials, as well as observational statistics, have exhibited that the advantages of antiretroviral [ARV] treatment for humans with Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome HIV/AIDS exceed their risks. Therapeutic drug monitoring [TDM] plays a key role in optimization of ARV therapy. Determination of ARV's in plasma, blood cells, and other biological matrices frequently requires separation techniques capable of high effectiveness, specific selectivity and high sensitivity. High-performance liquid chromatography [HPLC] coupled with ultraviolet [UV], Photodiode array detectors [PDA], Mass spectrophotometer [MS] detectors etc. are the important quantitative techniques used for the estimation of pharmaceuticals in biological samples. Objective: This review article is aimed to give an extensive outline of different bio-analytical techniques which have been reported for direct quantitation of ARV's. This article aimed to establish an efficient role played by the TDM in the optimum therapeutic outcome of the ARV treatment. It also focused on establishing the prominent role played by the separation techniques like HPLC and UPLC along with the detectors like UV and Mass in TDM. Methods: TDM is based on the principle that for certain drugs, a close relationship exists between the plasma level of the drug and its clinical effect. TDM is of no value if the relationship does not exist. The analytical methodology employed in TDM should: 1) distinguish similar compounds; 2) be sensitive and precise and 3) is easy to use Results: This review highlights the advancement of the chromatographic techniques beginning from the HPLC-UV to the more advanced technique like UPLC-MS/MS. TDM is essential to ensure adherence, observe viral resistance and to personalize ARV dose regimens. It is observed that the analytical methods like immunoassays and liquid chromatography with detectors like UV, PDA, Florescent, MS, MS/MS and Ultra performance liquid chromatography (UPLC)-MS/MS have immensely contributed to the clinical outcome of the ARV therapy. Assay methods are not only helping physicians in limiting the side effects and drug interactions but also assisting in monitoring patient's compliance. Conclusion: The present review revealed that HPLC has been the most widely used system irrespective of the availability of more sensitive chromatographic technique like UPLC.VRAID (ex DIPUC

The association of therapeutic versus recreational marijuana use and antiretroviral adherence among adults living with HIV in Florida

Zachary L Mannes,1 Larry E Burrell II,1 Erin G Ferguson,1 Zhi Zhou,2,3 Huiyin Lu,4,5 Charurut Somboonwit,6 Robert L Cook,2,3 Nicole Ennis1 1Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; 2Department of Epidemiology, College of Public Health and Health Professions, 3Department of Epidemiology, College of Medicine, University of Florida, Gainesville, FL, USA; 4Department of Biostatistics, College of Public Health and Health Professions, 5Department of Biostatistics, College of Medicine, University of Florida, Gainesville, Florida, USA; 6Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA Purpose: Marijuana use is common among people living with HIV (PLWH), but its association with antiretroviral therapy (ART) adherence is unclear. This study examined the association between reason for marijuana use and ART adherence in a sample of adults living with HIV. Patients and methods: Participants (N=703) recruited from seven community health centers in Florida completed a 45-minute questionnaire assessing demographics, symptoms of anxiety and depression, ART adherence, and substance use, including reasons for marijuana use. ART adherence was defined as the proportion of days in the last 30 days participants did not miss any medication and dichotomized as optimal (&ge;95%) and suboptimal (&lt;95%). Multivariate logistic regression analysis assessed the association between therapeutic marijuana use to manage HIV symptoms (ie, improve appetite/gain weight, induce sleep, relieve nausea/vomiting, relieve pain, relieve anxiety/depression/stress) versus recreational marijuana use and ART adherence. Results: Approximately one third (33.2%) of the participants reported using marijuana in the past 3 months. Of marijuana users, 21.8% reported using marijuana only for therapeutic purposes to manage HIV-associated medical symptoms, while 78.2% reported recreational use. After controlling for covariates, therapeutic use of marijuana was not associated with ART adherence (AOR =1.19, 95% CI =0.60&ndash;2.38, p=0.602) while recreational marijuana users showed significantly greater odds of suboptimal ART adherence compared to nonusers (AOR =1.80, 95% CI =1.18&ndash;2.72, p=0.005). Conclusion: Our results suggest differences in ART adherence between individuals who report recreational versus therapeutic marijuana use. Continued research examining the health implications of marijuana use among adults living with HIV is important as legalization of recreational and medical marijuana proliferates in the United States. Keywords: HIV/AIDS, marijuana use, antiretroviral therapy, antiretroviral adherenc

Impact of early versus deferred antiretroviral therapy on estimated glomerular filtration rate in HIV-positive individuals in the START trial

The impact of early ART initiation (versus deferring) on kidney function has not been studied. START was a randomised comparison of immediate versus deferred ART initiation among HIV-positive persons with CD4(+) (cellsimm(3)) counts >500. Serum creatinine and urine dipstick protein were measured at Months 0, 1, 4, 8 and 12, and annually thereafter. The two arms were compared for changes in eGFR (mL/min/1.73 m(2), calculated by CI94% and >19% of follow-up time, respectively. Overall, 89% started ART using a tenofovir-based regimen. Over 2.1 years median follow-up, mean eGFR was 056 (95% CI 0.003-1.11) higher in the immediate versus deferred arm, which was more prominent after adjustment for current tenofovir or bPI use (1.85, 95% CI 1.21-2.50) and in Black participants (30.1% overall) (3.90, 95% CI 2.84-4.97) versus non-Blacks (1.05, 95% CI 0.33-1.77) (P <0.001 for interaction). Relative risk for proteinuria in the immediate versus deferred arm was 0.74 (95% CI 0.55-1.00) (P = 0.049). In the short-term, immediate ART initiation was associated with a modestly higher eGFR and lower proteinuria risk versus deferring ART (more pronounced in Black participants). Whether this early benefit translates into a lower risk of CKD requires further follow-up. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.Peer reviewe

Relationship between inflammatory and coagulation biomarkers and cardiac autonomic function in HIV-infected individuals

AIM: To examine the relationship between inflammatory and coagulation biomarkers and cardiac autonomic function (CAF) as measured by heart rate variability in persons with HIV. MATERIALS & METHODS: This analysis included 4073 HIV-infected persons from the Strategies for Management of Antiretroviral Therapy study. We examined the association between IL-6, high-sensitivity C-reactive protein (hsCRP) and d-dimer with heart rate variability measures (SDNN and rMSSD), both cross-sectionally and longitudinally. RESULTS: Cross-sectional analysis revealed significant inverse associations between IL-6, hsCRP and d-dimer with SDNN and rMSSD (p < 0.01 for all comparisons). However, longitudinal analysis failed to show a significant association between baseline IL-6, hsCRP and d-dimer with change in CAF over time. CONCLUSION: Cross-sectionally, higher levels of inflammatory and coagulation biomarkers were associated with lower levels of CAF in the Strategies for Management of Antiretroviral Therapy trial. Although deterioration in CAF was observed during followup, baseline levels of inflammatory and coagulation markers were not predictive of the decline in CAF over time