Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study

Abstract

Background: An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.

Methods: Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.

Results: 152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.

Conclusions: Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.

Keywords: Antiretroviral therapy; HIV; Human immunodeficiency virus; Salvage; Third-line; Virologic failure.

Fig. 1

Kaplan–Meier curves showing time to virologic suppression or death. a, b Show Kaplan–Meier estimates of time to suppression of HIV viral load ≤400 and 50 copies/ml respectively. All 152 patients were included in these analyses and patients were censored at death, loss to the programme or on 30 April 2014. The median time to suppression ≤400 copies/ml was 194 days and to ≤50 copies/ml was 368 days. Viral load measurements were generally performed 6 monthly, partly explaining the delayed suppression; c shows Kaplan–Meier estimates of time to death analysis. Patients were censored at 30 April 2014 for this analysis (vital status was known for all patients on this date)

Fig. 2

CD4 count prior to start of salvage ART and at 6 months intervals on salvage ART. The graph shows the median and interquartile range for CD4 counts (for those patients who had CD4 count performed) prior to starting ART salvage, then at 6 months intervals on salvage ART (with a ±3 month window for each 6 month interval)