Detection of HIV Virologic Failure and Switch to Second-Line Therapy: A Systematic Review and Meta-analysis of Data From Sub-Saharan Africa

Background: The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved.

Methods: We searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF-or at second-line ART switch-over time. We also explored temporal trends in delay between VF and switch to second-line ART.

Results: We identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm³ (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, -7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm³ (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (-14 days/year; 95% CI, -58 to 52).

Conclusions: VF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch.