CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

467 SUBOPTIMAL IMMUNE RECOVERY DESPITE SUPPRESSIVE ANTIRETROVIRAL THERAPY IN AFRICA

Stefanie Kroeze 1 , Pascale Ondoa 1 , Cissy Kityo 2 , Margaret Siwale 3 , Sonia Boender 1 , Peter Reiss 4 , Ferdinand Wit 4 , Tobias F. Rinke de Wit 1 , Raph L. Hamers 1 , for the PASER Study Group 1 Amsterdam Inst for Global Hlth and Development, Amsterdam, Netherlands, 2 Joint Clinical Rsr Cntr, Kampala, Uganda, 3 Lusaka Trust Hosp, Lusake, Zambia, 4 Stichting HIV Monitoring and Academic Med Cntr Amsterdam, Amsterdam, Netherlands Background: Suboptimal immune recovery (SO-IR), during suppressive antiretroviral therapy (ART), is associated with an increased risk of HIV-related illnesses, but has not been well-documented in African populations. We assessed SO-IR occurrence, defined by failure to attain clinically relevant thresholds of CD4 cell counts, factors associated with SO-IR, and incidence of tuberculosis (TB), AIDS or death during 6 years of ART within a large cohort. Methods: The Pan-African Studies to Evaluate Resistance (PASER) cohort comprises HIV-1 infected adults from Kenya, Nigeria, South Africa, Uganda, Zambia and Zimbabwe. Participants included in this analysis initiated first-line non-nucleoside reverse transcriptase inhibitor-based ART and had viral load (VL) <50 cps/mL after 1 year. VL testing was done annually. SO-IR was defined as proportions of participants with CD4<200, <350 and <500 cells/µL after 6 years of ART. Participants were censored at death, loss to follow- up, or at their last VL<50 cps/mL (if subsequent VL≥50 cps/mL). Incidence of TB, AIDS, or death was calculated per CD4 category and factors associated with SO-IR were assessed using Cox-regression. Results: 1,581 participants initiated ART, had VL<50 cps/mL after 12 months, and ≥1 CD4 count available; 61%were women, median age was 37 years (IQR 31-43), and median pre-ART CD4 count was 148 cells/µl (IQR 77-215), with 99%<350 and 70%<200 cells/µL. Total follow-up time was 5245 person-years (PYR). Proportions of SO-IR<200, <350, <500 cells/µL were 7.4, 27.2, 57.6% after 6 years. Per CD4 category <200, 200-350, 350-500 and >500 cells/µl, AIDS incidence was 4.4 (95%CI 3.2-5.6), 1.3 (0.9-2.0), 0.5 (0.2-1.1) and 0.4 (0.2-1.0) events/100PYR; TB incidence 3.3 (2.4-4.6), 0.8 (0.5-1.4), 0.4 (0.2-1.0) and 0.2 (0.1-0.8) events/100PYR; mortality 0.7 (0.4-1.4), 0.5 (0.2-1.0), 0.1 (0.0-0.6) and 0.7 (0.3-1.3)/100PYR. Baseline factors associated with failure to attain CD4≥500 were increasing age, male sex, and pre-ART CD4<200 cells/µL; additionally, subtype A, C or other (compared to D) was associated with failure to attain CD4≥350 and CD4≥200 (table). Conclusion: SO-IR is frequent in African adults, with the majority not attaining the CD4>500 cells/µL threshold after 6 years of ART. In our cohort, persons with SO-IR had an increased risk of TB and AIDS, but not death. This warrants close clinical and laboratory monitoring and emphasizes the importance of early ART initiation. 468 CURRENT STATIN USE REDUCES RISK OF VIRAL REBOUND ON SUPPRESSIVE CART Henning J. Drechsler 1 , Colby Ayers 2 , James Cutrell 1 , NaimMaalouf 3 , Pablo Tebas 4 , Roger Bedimo 1 1 VA North Texas Hlth Care Cntr, Dallas, TX, USA, 2 Univ of Texas Southwestern, Dallas, TX, USA, 3 Univ of Texas Southwestern Med Cntr, Dallas, TX, USA, 4 Univ of Pennsylvania, Philadelphia, PA, USA Background: Pleiotropic effects of statins include improvement of endothelial dysfunction, increased nitric oxide, antioxidant and anti-inflammatory properties, and stabilization of atherosclerotic plaques. Statins are also active against HIV-1 in vitro; however, they have never been shown to have an antiviral effect in clinical studies. Given their short half-lives, a modest virologic effect of statins is difficult to prove during cART and may require the analysis of continuous exposure. We hypothesized that continuous use of statins would increase the durability of successful cART. Methods: We examined the time to virologic rebound after reaching an undetectable viral load (VL) in all HIV infected US-veterans who started successful cART 1995-2011, had a VL >1000 copies/mL before, and had ≥1 follow up VL within 13 months of reaching undetectability. We defined virologic failure (VF) as any VL >1,000 copies/mL or the first of 2 consecutive VL >200 copies/mL. To address bias by indication and control for adherence, we used pharmacy refill data to build a time-updated drug exposure model for cART, statins, and other cardiovascular drugs (CVMs). We determined ever use, current use, and 30-day use rate [percentage of days covered (PDC)] We used both multiply adjusted and inverse-probability-weighted (IPW) Cox models to explore the association between statin use and VF. Results: We included 19,324 veterans. Median follow-up until the first viral rebound was 15 months (IQR: 6-40); 55% experienced VF. Almost 1/3 patients ever used statins but exposure was discontinuous with only 41% of follow-up time covered after initial exposure. The unadjusted hazard ratio (HR) for VF for current statin use was 0.60 (95%CI: 0.56- 0.65). This association persisted after multivariate adjustment for demographics, HIV and cART parameters [HR 0.81 (CI: 0.75-0.88), p<0.001] and IPW [HR: 0.86 (CI: 0.78-0.96), p=0.001, see Table]. This was not observed for current use of other CVMs. The PDC model yielded similar results (not shown). There was no independent association between ever-statin use and VF. Conclusion: Current statin exposure reduces the risk of VF in univariate, multivariate and inverse-probability-weighted models suggesting that statins have a modest antiviral activity in vivo. Whether this effect is direct or mediated by their anti-inflammatory properties merits further evaluation. In addition to their cardiovascular benefits, statins could increase the durability of successful antiretroviral therapy. 469 HIV-RELATED PILL AVERSION: CHARACTERIZING A NOVEL BARRIER TO ADHERENCE Robin Dorman, Sarah H. Sutton, Lynn M. Yee Northwestern Univ, Chicago, IL, USA Background: Pill aversion, defined as difficulty swallowing pills without identifiable medical cause as well as anxiety associated with pill swallowing, is a poorly-characterized barrier to sustained viral suppression in HIV-infected adults. We aimed to determine the prevalence of pill aversion in an adult outpatient HIV population and describe the relationship between symptoms and skipping pills. Methods: This was an observational study of HIV-infected individuals at a single urban tertiary care center. Participants attending HIV clinic were asked to complete anonymous questionnaires about their experience of swallowing HAART pills. The primary outcome was skipping pills due to pill aversion symptoms; this was defined as any affirmative response regarding skipping pills due to feeling uncomfortable taking them, problems swallowing them, or pill qualities. Descriptive statistics and bivariable analyses were used as appropriate. Multivariable logistic regression was utilized to determine factors associated with skipping pills. Results: Of 312 participants (mean age 47.8y), a majority were male (74.8%) and identified as white (48.4%) or non-Hispanic black (NHB; 40.8%). Nearly a quarter (24.8%) skipped pills due to pill aversion symptoms. Younger age, being NHB or Hispanic compared to white and having public insurance were associated with skipping pills due to pill aversion. Depression (27.6%) and anxiety (21.2%) were common and associated with pill aversion on bivariable analyses, but this association did not persist on multivariable analysis. Individuals who skipped pills were more likely to report a detectable viral load (25.7% vs. 8.5%, p=0.001) and have a lower self-reported adherence (79.4% vs. 94.9%, p<0.001). Importantly, participants who skip pills were more likely to report negative or fear-based emotions about their pills (Table). Participants who skipped pills were more likely to report sensations of gagging (13.5% vs 5.0%, p=0.013), choking (9.5% vs 1.8%, p=0.003), pills getting stuck in the throat (24.3% vs 9.0%, p=0.001), a heavy feeling in the stomach (18.9% vs 0.9%, p<0.001), as well as being bothered by the taste, smell, and size of pills (all p<0.001). Conclusion: HIV-related pill aversion is surprisingly frequent. Symptoms of pill aversion are a significant and novel barrier to adherence in an adult HIV population. Further investigation regarding generalizability, prevalence, and characterization of pill aversion is essential and may have implications for the cascade of care. 470 LONG-TERM EFFECTS OF IMMEDIATE VERSUS DEFERRED C-ART IN PRIMARY HIV INFECTION (PHI) Kees Brinkman , Sebastian Tawil, Guido van den Berk, Daoud Ait Moha, Willem Blok OLVG, Amsterdam, Netherlands Background: In primary HIV infection Immediate (but transient) cART suggests an immunological benefit over deferred cART; clinical benefits have not been reported. There are no studies on continuous cART in this setting. Here we studied the long-term effects of immediate (continuous) cART on immune recovery, mortality and clinical events in comparison with deferred cART in persons with PHI.

Poster and Themed Discussion Abstracts

CROI 2017 196