Long-Term Outcome of Second-Line Antiretroviral Therapy in Resource-Limited Settings

Abstract

There is limited information on efficacy and durability of second-line antiretroviral therapy (2NL) beyond 12 months in resource-limited settings. A total of 73 patients were enrolled into a prospective 2NL observational cohort in Nigeria. Second-line antiretroviral therapy consisted of lopinavir/ritonavir plus nucleoside reverse transcriptase inhibitors. Time on 2NL ranged from 15 to 31 months. Genotypes were retrospectively done and not available to guide second-line regimen choice. At enrollment, median CD4 count was 121 cells/mm3, and median time on first-line antiretroviral therapy (ISL) was 24 months. At 6 to 9 months on 2NL, 72.6% (intention to treat [ITT]) and 88.3% (on treatment [OT]) had an undetectable viral load (UDVL). At 12 months, 65.8% (ITT) and 90.57% (OT) had UDVL. At >12 to 24 months and at >24 months, 57.5% (ITT) and 91.3% (OT) had UDVL. No statistically significant association was observed between CD4 at 2NL start, sex, genotypic sensitivity score of 2NL, or tenofovir (TDF) use in ISL and viral suppression. Two patients developed major protease inhibitor mutations while on 2NL. We observed a high degree of viral suppression at 12 months and little loss of viral suppression thereafter.

Treatment outcomes of over 1000 patients on second‐line, protease inhibitor‐based antiretroviral therapy from four public‐sector HIV treatment facilities across Johannesburg, South Africa

“…Patients with higher viral loads and lower CD4 counts at the time of switch to second line were at greater risk for attrition and were less likely to experience virologic suppression. These findings are similar to those reported elsewhere, but the larger sample size and longer follow‐up time aid in making inferences . While drug resistance testing is not routinely conducted, previous research has shown that suboptimal adherence is likely to be the primary driver of virologic failure on second‐line ART .…”

“…Numerous programmes in resource‐limited settings have demonstrated successful treatment outcomes of first‐line therapy. Fewer, however, have described the treatment outcomes of second‐line therapy, with evidence mainly restricted to smaller cohorts with limited information on efficacy and durability of second‐line ART beyond 1 year . Nonetheless, programmes that have reported outcomes have shown mixed results.…”

HIV drug Resistance Mutations among Patients Failing Second-Line Antiretroviral Therapy in Rwanda

“…This study was the first to identify and analyse DRMs in HIV-infected patients failing second-line ART regimens in Rwanda. Little data exists for DRMs in patients failing second-line ART in Africa [4,6]. Of patients with successful genotype analyses, more than one-third demonstrated no evidence of resistance, while 30% had DRMs to at least one class of ARVs.…”

“…However, as in other resource-limited settings (RLS), viral load (VL) monitoring during the initial scale-up period was not routinely available. Patients failing first-line ART regimens were at risk of acquisition and accumulation of HIV drug resistance mutations (DRMs) that could compromise effectiveness of secondline ART regimens [2][3][4].…”

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

“…Viral failure was identified less often than one might expect from other second-line studies, 20–25 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.…”