Predictors of first-line antiretroviral therapy failure among adults and adolescents living with HIV/AIDS in a large prevention and treatment program in Nigeria

Abstract

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 mm3 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 mm3, and the mean HIV-1 RNA was 3.3 ± 1.3.log10 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 mm3 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 mm3 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.

Factors Associated With Virological Suppression of HIV Viral Load in Patients on Antiretroviral Therapy in Conakry, Guinea

“…Patients on rst-line ART were more likely to experience viral load suppression. This result is consistent with other authors' observations that the rst-line regimen should be initiated in all HIV-positive people starting treatment (14,19,20). As argued by some authors for the change from the former to the latter (21).…”

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria

“…For example, an analysis from the same study site found that one-fifth of Sanger sequences from 198 people who had failed first-line ART had no detectable drug resistance mutations. 37 This may reflect complete non-adherence or very poor adherence, in which case a switch to second-line ART would not be common practice. On the other hand, other studies have shown that extensive resistance does occur when people remain on failing NNRTI-based regimens long term.…”

Disengagement From HIV Care and Failure of Second-Line Therapy in Nigeria: A Retrospective Cohort Study, 2005–2017

“…This mirrors the results from previous first-line ART studies from sub-Saharan Africa that have shown clinical and immunologic failure to be poor predictors of viral failure during first-line ART. 10,[17][18][19] Viral failure was identified less often than one might expect from other second-line studies, [20][21][22][23][24][25] particularly when considering the long follow-up period of this analysis. However, the low frequency of viral load measurements, which was only done in 55% of participants, meant that this is likely to be an underestimate of the true proportion of the cohort that had viral failure.…”

“…This mirrors the results from previous first-line ART studies from sub-Saharan Africa that have shown clinical and immunologic failure to be poor predictors of viral failure during first-line ART. 10,17–19…”