PMID- 30043384 OWN - NLM STAT- MEDLINE DCOM- 20190312 LR - 20190312 IS - 1179-1942 (Electronic) IS - 0114-5916 (Print) IS - 0114-5916 (Linking) VI - 41 IP - 12 DP - 2018 Dec TI - Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa. PG - 1343-1353 LID - 10.1007/s40264-018-0698-3 [doi] AB - INTRODUCTION: Understanding the occurrence of antiretroviral (ARV)-related adverse events (AEs) among patients receiving second-line antiretroviral therapy (ART) is important in preventing switches to more limited and expensive third-line regimens. OBJECTIVE: This study aimed to estimate the rates and examine predictors of AEs among adult HIV-1-infected patients receiving second-line ART in the Right to Care (RTC) clinical cohort in South Africa. METHODS: This was a cohort study of HIV-1-infected adult patients (>/= 18 years of age) initiating standard second-line ART in South Africa from 1 April 2004 to 10 January 2016. Our primary outcome was the development of an AE within 24 months of initiating second-line therapy. We used Kaplan-Meier survival analysis to determine AE incidence in the first 24 months of second-line ART. Predictors of AEs were modelled using a Cox proportional hazards model. RESULTS: A total of 7708 patients initiated second-line ART, with 44.5% developing at least one AE over the first 24 months of second-line treatment. The highest AE incidence was observed among patients receiving abacavir (ABC) + lamivudine (3TC) + ritonavir-boosted lopinavir/atazanavir (LPVr/ATVr) (52.7/100 person-years (PYs), 95% confidence interval (CI): 42.9-64.8), while patients initiated on a tenofovir (TDF) + emtricitabine (FTC)/3TC + LPVr regimen had the lowest rate of AEs (26.4/100 PYs, 95% CI: 24.9-28.3). Clinical predictors of AEs included experiencing AEs when receiving first-line ART (adjusted hazard ratio (aHR) 2.3, 95% CI: 1.9-2.8), lower CD4 cell count (0-199 vs. >/= 350 cells/mm(3); aHR 1.4, 95% CI: 1.4-1.8), and switching to second-line therapy from an ABC-base first-line regimen (ABC + 3TC + efavirenz/nevirapine [EFV/NVP] vs. TDF + 3TC/FTC + EFV/NVP; aHR 3.4, 95% CI: 1.1-11.1). CONCLUSIONS: The rates of AEs were lowest among patients receiving a TDF-based second-line regimen. Patients with poorer health at the time of switch were at higher risk of AEs when receiving second-line ART and may require closer monitoring to improve the durability of second-line therapy. FAU - Onoya, Dorina AU - Onoya D AUID- ORCID: 0000-0002-2664-7342 AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 39 Empire Road, Empire Park, Parktown, Johannesburg, 2193, South Africa. donoya@heroza.org. FAU - Hirasen, Kamban AU - Hirasen K AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 39 Empire Road, Empire Park, Parktown, Johannesburg, 2193, South Africa. FAU - van den Berg, Liudmyla AU - van den Berg L AD - Right to Care, Johannesburg, South Africa. FAU - Miot, Jacqui AU - Miot J AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 39 Empire Road, Empire Park, Parktown, Johannesburg, 2193, South Africa. FAU - Long, Lawrence C AU - Long LC AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 39 Empire Road, Empire Park, Parktown, Johannesburg, 2193, South Africa. AD - Department of Global Health, Boston University School of Public Health, Boston, MA, USA. FAU - Fox, Matthew P AU - Fox MP AD - Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, 39 Empire Road, Empire Park, Parktown, Johannesburg, 2193, South Africa. AD - Department of Global Health, Boston University School of Public Health, Boston, MA, USA. AD - Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - New Zealand TA - Drug Saf JT - Drug safety JID - 9002928 RN - 0 (Anti-HIV Agents) RN - 0 (Anti-Retroviral Agents) SB - IM MH - Adolescent MH - Adult MH - Anti-HIV Agents/*adverse effects MH - Anti-Retroviral Agents/*adverse effects MH - Cohort Studies MH - Drug-Related Side Effects and Adverse Reactions/diagnosis/*epidemiology MH - Female MH - Follow-Up Studies MH - HIV Infections/*drug therapy/*epidemiology MH - *HIV-1 MH - Humans MH - Male MH - Prospective Studies MH - South Africa/epidemiology MH - Young Adult PMC - PMC6223700 COIS- CONFLICT OF INTEREST: Dorina Onoya, Kamban Hirasen, Liudmyla van den Berg, Jacqui Miot, Lawrence C. Long and Matthew P. Fox have no conflicts of interest that are directly relevant to the content of this study. ETHICAL APPROVAL: All data were fully anonymised for analyses. Ethics approval for the retrospective data review was obtained from the Human Research Ethics Committee of the University of Witwatersrand (M140201) and the Boston University Institutional Review Board (H-29768). PATIENT CONSENT: Following Sect. 3 of the recommendations regarding the provisions for waiver or alteration of the informed consent requirements under the South African Department of Health and Human Services (HHS) Regulations at 45 CFR 46.116(d) and the Declaration of Helsinki, a waiver for individual patient consent was obtained. EDAT- 2018/07/26 06:00 MHDA- 2019/03/13 06:00 PMCR- 2018/07/24 CRDT- 2018/07/26 06:00 PHST- 2018/07/26 06:00 [pubmed] PHST- 2019/03/13 06:00 [medline] PHST- 2018/07/26 06:00 [entrez] PHST- 2018/07/24 00:00 [pmc-release] AID - 10.1007/s40264-018-0698-3 [pii] AID - 698 [pii] AID - 10.1007/s40264-018-0698-3 [doi] PST - ppublish SO - Drug Saf. 2018 Dec;41(12):1343-1353. doi: 10.1007/s40264-018-0698-3.