PMID- 33143751 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20210917 IS - 1742-6405 (Electronic) IS - 1742-6405 (Linking) VI - 17 IP - 1 DP - 2020 Nov 3 TI - Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria. PG - 64 LID - 10.1186/s12981-020-00317-9 [doi] LID - 64 AB - BACKGROUND: A substantial number of persons living with HIV (PLWH) in Nigeria do not experience durable viral suppression on first-line antiretroviral therapy (ART). Understanding risk factors for first-line treatment failure informs patient monitoring practices and distribution of limited resources for second-line regimens. We determined predictors of immunologic and virologic failures in a large ART delivery program in Abuja, Nigeria. METHODS: A retrospective cohort study was conducted at the University of Abuja Teaching Hospital, a tertiary health care facility, using data from February 2005 to December 2014 in Abuja, Nigeria. All PLWH aged >/= 15 years who initiated ART with at least 6-month follow-up and one CD4 measurement were included. Immunologic failure was defined as a CD4 decrease to or below pre-ART level or persistent CD4 < 100 cells per mm(3) after 6 months on ART. Virologic failure (VF) was defined as two consecutive HIV-1 RNA levels > 1000 copies/mL after at least 6 months of ART and enhanced adherence counselling. HIV drug resistance (Sanger sequences) was analyzed using the Stanford HIV database algorithm and scored for resistance to common nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Univariate and multivariate log binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: Of 12,452 patients followed, a total of 5928 initiated ART with at least 6 months of follow-up and one CD4 measurement. The entry point for 3924 (66.2%) was through the program's own voluntary counseling and testing (VCT) center, while 1310 (22.1%) were referred from an outside clinic/program, 332 (5.6%) in-patients, and 373 (6.3%) through other entry points including prevention of mother to child transmission (PMTCT) and transferred from other programs. The mean CD4 at enrollment in care was 268 +/- 23.7 cells per mm(3), and the mean HIV-1 RNA was 3.3 +/- 1.3.log(10) copies/mL. A total of 3468 (80.5%) received nevirapine (NVP) and 2260 (19.5%) received efavirenz (EFV)-based regimens. A total of 2140 (36.1%) received tenofovir (TDF); 2662 (44.9%) zidovudine (AZT); and 1126 (19.0%) stavudine (d4T). Among those receiving TDF, 45.0% also received emtricitabine (FTC). In a multivariate model, immunologic failure was more common among PLWH with female gender as compared to male [RR (95% CI) 1.22 (1.07-1.40)] and less common among those who entered care at the program's VCT center as compared to other entry points [0.79 (0.64-0.91)], WHO stage 3/4 as compared to 1/2 [0.19 (0.16-0.22)], or CD4 200 + cells per mm(3) as compared to lower [0.19 (0.16-0.22)]. Virologic failure was more common among PLWH who entered care at the program's VCT center as compared to other entry points [RR (95% CI) 1.45 (1.11-1.91) and those with CD4 < 200 cells per mm(3) at entry into care as compared to higher [1.71 (1.36-2.16)]. Of 198 patient-derived samples sequenced during virologic failure, 42 (21%) were wild-type; 145 (73%) carried NNRTI drug resistance mutations; 151 (76.3%) M184I/V; 29 (14.6%) had >/= 3 TAMs, and 37 (18.7%) had K65R, of whom all were on TDF-containing first-line regimens. CONCLUSIONS: In this cohort of Nigerian PLWH followed for a period of 9 years, immunologic criteria poorly predicted virologic failure. Furthermore, a subset of samples showed that patients failing ART for extended periods of time had HIV-1 strains harboring drug resistance mutations. FAU - Ndembi, Nicaise AU - Ndembi N AUID- ORCID: 0000-0002-9498-3428 AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. nicaise.ndembi@gmail.com. AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. nicaise.ndembi@gmail.com. FAU - Murtala-Ibrahim, Fati AU - Murtala-Ibrahim F AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. FAU - Tola, Monday AU - Tola M AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. FAU - Jumare, Jibreel AU - Jumare J AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Aliyu, Ahmad AU - Aliyu A AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. FAU - Alabi, Peter AU - Alabi P AD - University of Abuja Teaching Hospital, Federal Capital Territory, Abuja, Nigeria. FAU - Mensah, Charles AU - Mensah C AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Abimiku, Alash'le AU - Abimiku A AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Quinones-Mateu, Miguel E AU - Quinones-Mateu ME AD - Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand. FAU - Crowell, Trevor A AU - Crowell TA AD - Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. AD - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. FAU - Rhee, Soo-Yon AU - Rhee SY AD - Department of Medicine, Stanford University, Stanford, CA, USA. FAU - Shafer, Robert W AU - Shafer RW AD - Department of Medicine, Stanford University, Stanford, CA, USA. FAU - Gupta, Ravindra AU - Gupta R AD - University College London, London, UK. FAU - Blattner, William AU - Blattner W AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Charurat, Manhattan E AU - Charurat ME AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Dakum, Patrick AU - Dakum P AD - Institute of Human Virology, Federal Capital Territory, 252 Herbert Macaulay Way, Abuja, Nigeria. AD - Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng GR - R24 AI136618/AI/NIAID NIH HHS/United States GR - U2G GH002099-01/U.S. President's Emergency Plan for AIDS Relief/International GR - PA GH17-1753 (ACHIEVE)/U.S. President's Emergency Plan for AIDS Relief/International GR - NIH R01AI147331-01 (RAI147331A)/National Institute of Health (US)/International PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20201103 PL - England TA - AIDS Res Ther JT - AIDS research and therapy JID - 101237921 RN - 0 (Anti-HIV Agents) SB - IM MH - Adolescent MH - Adult MH - *Anti-HIV Agents/pharmacology/therapeutic use MH - Drug Resistance, Viral MH - Female MH - *HIV Infections/drug therapy/epidemiology/prevention & control MH - Humans MH - Infectious Disease Transmission, Vertical MH - Male MH - Nigeria MH - Retrospective Studies MH - Treatment Failure MH - Viral Load PMC - PMC7640637 COIS- The authors have no conflicts of interest. EDAT- 2020/11/05 06:00 MHDA- 2021/09/18 06:00 PMCR- 2020/11/03 CRDT- 2020/11/04 05:31 PHST- 2019/11/20 00:00 [received] PHST- 2020/09/10 00:00 [accepted] PHST- 2020/11/04 05:31 [entrez] PHST- 2020/11/05 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2020/11/03 00:00 [pmc-release] AID - 10.1186/s12981-020-00317-9 [pii] AID - 317 [pii] AID - 10.1186/s12981-020-00317-9 [doi] PST - epublish SO - AIDS Res Ther. 2020 Nov 3;17(1):64. doi: 10.1186/s12981-020-00317-9.