PMID- 28830382 OWN - NLM STAT- MEDLINE DCOM- 20171109 LR - 20231112 IS - 1471-2334 (Electronic) IS - 1471-2334 (Linking) VI - 17 IP - 1 DP - 2017 Aug 22 TI - Rates of switching to second-line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among HIV-infected adults with virologic failure in Rakai, Uganda. PG - 582 LID - 10.1186/s12879-017-2680-6 [doi] LID - 582 AB - BACKGROUND: Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90' of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005. METHODS: Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of >/=50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients. RESULTS: The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9-6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 >/= 100 cells/ul (aHR = 2.30, 95% CI = 1.5-3.6). Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases. CONCLUSIONS: Intervention strategies that aid clinicians to promptly switch patients to second-line ART as soon as virologic failure on 1st line ART is confirmed should be prioritized. FAU - Ssempijja, Victor AU - Ssempijja V AUID- ORCID: 0000-0003-2609-6525 AD - Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., NCI Campus at Frederick, Frederick, MD, 21702, USA. victor.ssempijja@nih.gov. AD - Clinical Monitoring Research Program (CMRP), Leidos Biomedical Research, Inc., 5705 Industry Lane, Frederick, MD, 21704, USA. victor.ssempijja@nih.gov. FAU - Nakigozi, Gertrude AU - Nakigozi G AD - Rakai Health Sciences Program, Kalisizo, Uganda. FAU - Chang, Larry AU - Chang L AD - Rakai Health Sciences Program, Kalisizo, Uganda. AD - Johns Hopkins School of Medicine, Baltimore, MD, USA. AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. FAU - Gray, Ron AU - Gray R AD - Rakai Health Sciences Program, Kalisizo, Uganda. AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. FAU - Wawer, Maria AU - Wawer M AD - Rakai Health Sciences Program, Kalisizo, Uganda. AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. FAU - Ndyanabo, Anthony AU - Ndyanabo A AD - Rakai Health Sciences Program, Kalisizo, Uganda. FAU - Kasule, Jingo AU - Kasule J AD - Rakai Health Sciences Program, Kalisizo, Uganda. FAU - Serwadda, David AU - Serwadda D AD - Rakai Health Sciences Program, Kalisizo, Uganda. AD - School of Public Health, Makerere University College of Health Sciences, Kampala, Uganda. FAU - Castelnuovo, Barbara AU - Castelnuovo B AD - Infectious Disease Institute, Makerere University College of Health Sciences, Kampala, Uganda. FAU - Hoog, Anja Van't AU - Hoog AV AD - Department of Global Health -Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. FAU - Reynolds, Steven James AU - Reynolds SJ AD - Rakai Health Sciences Program, Kalisizo, Uganda. AD - Johns Hopkins School of Medicine, Baltimore, MD, USA. AD - Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. AD - Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. LA - eng GR - Z01 AI001040/AI/NIAID NIH HHS/United States GR - HHSN261200800001E/CA/NCI NIH HHS/United States GR - D43 TW009771/TW/FIC NIH HHS/United States GR - PEPFAR/PEPFAR/ PT - Journal Article DEP - 20170822 PL - England TA - BMC Infect Dis JT - BMC infectious diseases JID - 100968551 RN - 0 (Anti-HIV Agents) SB - IM MH - Adolescent MH - Adult MH - Anti-HIV Agents/*therapeutic use MH - CD4 Lymphocyte Count MH - Female MH - HIV Infections/*drug therapy/virology MH - Humans MH - Incidence MH - Male MH - Proportional Hazards Models MH - Retrospective Studies MH - Time Factors MH - Treatment Failure MH - Uganda MH - Viral Load MH - Young Adult PMC - PMC5568262 OTO - NOTNLM OT - *Antiretroviral therapy OT - *Cohort studies OT - *Competing risk model OT - *HIV OT - *Mortality OT - *Second line antiretroviral therapy OT - *Treatment switch OT - *Virologic failure COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: The retrospective use of de-identified, routinely collected clinical data was approved by the Uganda Virus Research Institute's Research and Ethics Committee, The Institutional Review Board for Johns Hopkins University School of Medicine, and the Uganda National Council for Science and Technology. Individual informed consent was not obtained. CONSENT FOR PUBLICATION: Not applicable. COMPETING INTERESTS: BC is a member of the editorial board for the BMC Infectious Diseases journal. Other authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2017/08/24 06:00 MHDA- 2017/11/10 06:00 PMCR- 2017/08/22 CRDT- 2017/08/24 06:00 PHST- 2017/04/23 00:00 [received] PHST- 2017/08/13 00:00 [accepted] PHST- 2017/08/24 06:00 [entrez] PHST- 2017/08/24 06:00 [pubmed] PHST- 2017/11/10 06:00 [medline] PHST- 2017/08/22 00:00 [pmc-release] AID - 10.1186/s12879-017-2680-6 [pii] AID - 2680 [pii] AID - 10.1186/s12879-017-2680-6 [doi] PST - epublish SO - BMC Infect Dis. 2017 Aug 22;17(1):582. doi: 10.1186/s12879-017-2680-6.