Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa

Abstract

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts.

Methods: We included 18,706 adult patients starting ART in South Africa and 80,937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months.

Results: In South Africa, 9.8% [95% confidence interval (CI) 9.1-10.5] had switched at 3 years, 1.3% (95% CI 0.9-1.6) remained on failing first-line regimens, 9.2% (95% CI 8.5-9.8) were lost to follow-up and 4.3% (95% CI 3.9-4.8) had died. In Malawi and Zambia, more patients were on a failing first-line regimen [3.7% (95% CI 3.6-3.9], fewer patients had switched [2.1% (95% CI 2.0-2.3)] and more patients were lost to follow-up [15.3% (95% CI 15.0-15.6)] or had died [6.3% (95% CI 6.0-6.5)]. Median CD4 cell counts were lower in South Africa at the start of ART (93 vs. 132 cells/μl; P < 0.001) but higher after 3 years (425 vs. 383 cells/μl; P < 0.001). The hazard ratio comparing South Africa with Malawi and Zambia after adjusting for age, sex, first-line regimen and CD4 cell count was 0.58 (0.50-0.66) for death and 0.53 (0.48-0.58) for loss to follow-up.

Conclusion: Over 3 years of ART mortality was lower in South Africa than in Malawi or Zambia. The more favourable outcome in South Africa might be explained by viral load monitoring leading to earlier detection of treatment failure, adherence counselling and timelier switching to second-line ART.

Figure 1

States and transitions between states in the multi-state model. ART= antiretroviral therapy

Figure 2

Cumulative mortality of patients starting antiretroviral therapy in four sites with routine viral load monitoring from the Republic of South Africa and two sites without access to routine viral load monitoring in Malawi and Zambia.

Figure 3

Cumulative probability of treatment outcomes from 6 months after starting antiretroviral therapy in sites with and without routine viral load monitoring in the Southern Africa IeDEA cohort. Failure relates to virological failure in viral load sites and immunological failure in non viral load sites and relates to patients who met criteria for failure but have not been switched to second-line therapy.

Figure 4

Evolution of CD4 cell counts from start of antiretroviral therapy (ART) up to three years after start of ART in four sites with routine viral load (Republic of South Africa) and two sites without access to viral load monitoring (Malawi and Zambia). Lines represent the mean fit of the mixed effect model with 95% confidence intervals, dots and crosses the moving averages of the observed data. Viral load sites are shown as broken lines and dots, non viral load sites as solid line and crosses.