CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

464 OUTCOMES AND SIDE EFFECTS OF PATIENTS ON ART FOR MORE THAN 10 YEARS IN MALAWI Sekai C. Mathabire 1 , Alia Tayea 1 , Joseph Bitilinyu-Bangoh 2 , Elkin H. Bermudez 1 , Leon Salumu 3 , Isabel A. Quiles 4 , Elisabeth Szumilin 3 , Zengani Chirwa 5 , Fernanda Rick 1 , David Maman 6 1 MSF France, Chiradzulu, Malawi, 2 Queen Elizabeth Central Hosp, Blantyre, Malawi, 3 MSF France, Paris, France, 4 MSF France, Lilongwe, Malawi, 5 Ministry of Hlth, Malawi, Lilongwe, Malawi, 6 Epicentre, Cape Town, South Africa Background: With the support of MSF, antiretroviral drugs (ART) have been available in Chiradzulu district, Malawi, since 2001. We conducted a cross-sectional study among individuals on ART for more than 10 years to assess long term clinical, immunological, virological outcomes and prevalence of major side effects. Methods: Participants from Chiradzulu, on ART for more than 10 years were identified using a routine electronic HIV cohort monitoring database and invited to participate in the cross-sectional study. Following informed consent, individual patient data was collected using a standard questionnaire, clinical examination was conducted and blood was collected for CD4 and viral load tests. The ACTG Brief Peripheral Neuropathy Screening Tool was used to assess peripheral neuropathy. Results: Of 7,117 patients who initiated ARV in Chiradzulu, between February 2001 and February 2006, 1,405(19.8%) died, 1,508 (21.2%) were lost to follow-up, 1,070(15.0%) transferred out and 3,134 (44.4%) were still alive and followed-up. Of them, 379 were randomly included in the study. They were mostly women (73.1%) and their median age was 47[IQR 42-53]. The median time on ART was 11.6 years (IQR 10.6-12.1) and 344 patients (91%) were on first line/alternative 1st line regimens, mostly on TDF based regimen (86.6%). At the time of the survey, most of the patients were WHO Stage 1 (89.3%; 95%CI 86.6-91.4), had a CD4 count above 500 cells/µL (61.4%; 95%CI 57.8-64.9) and were virally suppressed (92.7%; 95%CI 90.6-94.4). A total 239 patients (63.1%) had a history of ART related toxicities that led to drug changes, with 176 (46.4%) and 53 (14.0%) due to Lipodystrophy and peripheral neuropathy, respectively. Facial atrophy was still common (55.3%) and was higher among those who started with D4T than those who started on AZT regimens (57.4% [95%CI: 52.0-62.6] versus 42.5% [95%CI: 28.3-58.1], p=0.02). Regarding peripheral neuropathy, 35.1% (95%CI 30.5-40.0) had at least one symptom (95%CI 30.5-40.0). Of them, 52.2% (95%CI 44.1-61.1) and 63.5% (95%CI 54.7-71.5) had abnormal reflexes and perceptions of tuning fork vibrations, respectively. Conclusion: Good clinical and virological outcomes were achieved among those retained in care. Probably due to long exposure to D4T, Lipodystrophy and peripheral neuropathy were common side-effects. 465 INCREASED PERSISTENCE OF INITIAL ART WITH INSTI-CONTAINING REGIMENS Thibaut Davy , Sonia Napravnik, Oksana Zakharova, Joseph J. Eron Univ of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: The durability of a first combination antiretroviral (cART) regimen is important to long-term sustained virologic suppression and immunologic recovery and influences treatment selection. In this study we aimed to estimate and compare the durability of the first cART regimen received by antiretroviral-naïve patients from 1996 through 2014. Methods: All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and Cox proportional hazards models adjusted for baseline age, sex, race, CD4 cell count, HIV RNA level, and calendar year. Results: The study population comprised 1,624 patients with a median age of 37 years (Interquartile Range [IQR]: 29, 46) at therapy initiation, CD4 cell count of 277 cells/mm3 (IQR: 104, 463), and a majority of African-American (60%) and male (72%) patients. Eleven percent initiated INSTI, 33% NNRTI, 20% bPI, 27% Other, and 9% NRTI-only regimens. Less than half of patients initiating INSTI experienced discontinuation or virologic failure with median times to event greater than 7.4 years for both outcomes; compared to 3.5 years for discontinuation and 5.1 years for virologic failure among patients initiating NNRTI (Figure, both log-rank p<0.01). Compared to NNRTI-containing regimens, INSTI- containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35, 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46, 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared to NNRTI. Conclusion: In the last 20 years, new agents with greater potency, safety and tolerability used in first regimens have led to notable increases in the durability of a first regimen. The recent introduction of INSTI based regimens as initial treatment in routine clinical care has led to substantial increases in first line regimen durability and decreased virologic failure. 466 DYNAMICS OF ULTRA-DEEP SUPPRESSED HIV VIREMIA (<5 CP/ML) IN CART-TREATED PATIENTS Alessandra Amendola , Adriana Ammassari, Assunta Navarra, Giulia Bibbolino, Carmela Pinnetti, Isabella Abbate, Gabriella Rozera, Annalisa Mondi, Enrico Girardi, Maria R. Capobianchi Natl Inst for Infectious Diseases Lazzaro Spallanzani, Rome, Italy

Poster and Themed Discussion Abstracts

Background: Residual viremia (RV; <50 c/ml HIV RNA) persists in up to 70-90% patients under successful cART over extended periods. Its role in loss of virologic control is controversial, since it has been found to predict virological rebound in some, but not all studies. Further, RV dynamics are still largely unknown. Our aimwas to monitor RV in effectively cART- treated patients for one year after viral suppression (VS; <50 c/ml) to assess the proportion of patients reaching ultra-deep suppressed viremia (USV; <5 c/ml) and the ability to maintain this condition. Methods: Sixty HIV-infected patients (49 with chronic HIV infection, 11 with primary HIV infection) on first-line cART, reaching and maintaining stable VS, were analysed (M/F 54/6; mean age 36 y; pre-cART median HIV RNA 4.89 log10 c/ml and mean CD4+ 382/mm3). HIV RNA viral load (VL) and RV were measured with standard and ultrasensitive (US) protocols of Abbott Real-Time HIV-1 assay (LLOD: 40 and 5 c/ml, respectively) at baseline (BL), at VS (T0), at month 6 (T1) and 12 (T2) after T0. Cox proportional hazard models were carried out to analyze factors associated with time to first USV and USV maintenance. Results: Overall, during first year of cART-induced continuous VS, a steady decrease of the median RV occurred: median RV log10 c/ml (IQR) at T0, T1 and T2 were 0.81 (0.40-1.23), 0.39 (0.00-0.78) and 0.18 (0.00-0.068), respectively. A significant difference was found for T0 vs T1 and To vs T2: p<0.0005. All patients achieved USV: 27 (45%) maintained USV throughout the study and, among them, 88.2% showed undetected HIV RNA with US at the end of follow-up. The remaining 33 patients, although with continuous VS, showed fluctuating levels of RV between 5-10 c/ml HIV RNA. Factors associated with the inability to maintain USV were [aHR, 95%IC]: pre-cART higher VL [2.14, 1.23-3.72], pre-cART CD4+<200/mm3 [3.97, 1.61-9.77], >12 weeks to achieve VS [2.51, 1.07-5.89] (Figure). Conclusion: After VS on first-line cART, a steady and significant reduction of RV is observed, suggesting progressive purging of viral reservoirs. In almost half of successfully-treated patients, USV is achieved and maintained throughout the first year of continuous VS. Pre-cART lower VL and higher CD4+ cells, together with faster VS achievement, were all associated to USV attainment. Early start of cART and use of potent cART are essential to lower RV and viral reservoirs in HIV-positive patients.

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