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Background: Characterizing viral response to lopinavir/ritonavir (LPV/r) monotherapy as second-line treatment may guide recommendations for resource-limited settings (RLS)., Methods: We conducted a 48-week prospective, single-arm study of LPV/r monotherapy in patients failing first-line therapy in Nigeria. The primary outcome was sustained HIV-1 viral load (VL) <400 copies/mL at 48 weeks., Results: Of 30 enrolled patients, 28 (93%) achieved viral suppression on LPV/r, while 29 (96%) experienced low-level viremia. At 48 weeks, 9 (30%) met the primary outcome of sustained viral suppression; 14 (47%) patients were suppressed on LPV/r in a snapshot analysis. Detectable VLs at 12 and 24 weeks were strongly associated with treatment failure at 48 weeks. New resistance mutations were not detected. The trial was stopped early due to treatment failure., Conclusion: In this study, the rate of virologic failure among patients on a second-line lopinavir monotherapy regimen was relatively high and predicted by early detectable viremia. However, no LPV/r-associated resistance mutations were detected despite fluctuating low-level viremia, demonstrating the high genetic barrier to resistance of the protease inhibitor class which could be useful in RLS.

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.

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.