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

Abstract

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.

Keywords: AIDS; Sub-Saharan Africa; advanced HIV; resource-limited settings; second-line antiretroviral therapy; virologic failure.

Figure 1.

Flowchart for search and selection strategy for studies in the meta-analysis of CD4 cell count at virologic treatment failure and at time of switch to second-line ART in Sub-Saharan Africa. Abbreviations: ART, antiretroviral therapy; VL, viral load.

Figure 2.

Mean CD4 cell count (cells/µL) among HIV patients at virologic failure, by country, for studies during the period of 2009–2020. There were no studies that reported CD4 cell counts at the time of switch to second-line ART between 2018 and 2020. One study from 2014 only reported mean and no standard deviation, represented by a circle. Abbreviation: ART, antiretroviral therapy.

Figure 3.

Mean CD4 count (cells/µL) +/-SE among HIV patients at the time of second-line ART switch, by country, for studies during the period of 2009–2020. Abbreviation: ART, antiretroviral therapy.

Figure 4.

Sensitivity analysis of mean CD4 count (95% CI) at virologic failure by country of origin (South Africa vs other) and clinic type (dedicated ART clinic vs other types). Abbreviation: ART, antiretroviral therapy.

Figure 5.

Mean time (+/-SE) from virologic failure to switch to second-line ART, in days, among HIV patients by country. Abbreviation: ART, antiretroviral therapy.