Among patients with sustained viral suppression in a resource-limited setting, CD4 gains are continuous although gender-based differences occur

Abstract

Introduction: There is conflicting data on long-term CD4 immune recovery after combination antiretroviral therapy (ART) in resource-limited settings. Virologic suppression is rarely documented in cohorts from sub-Saharan Africa so objective evidence of adherence is biologically unsubstantiated. We sought to investigate long-term patterns of immune recovery in Ugandan patients on ART with sustained viral suppression.

Methods: A prospective cohort of patients starting ART between April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained viral suppression (viral load ≤ 400 copies/ml at month 6 and 12) while on first-line ART. Propensity scores were used to adjust for treatment allocation (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan Meier methods and cross-sectional time series regression.

Results: Three hundred and fifty-six patients were included in the analysis.71.6% were female, 87% in WHO stage 3 or 4, median age was 37 years, (IQR:32-43), and median CD4 count was 108 cells/µL, (IQR:35-174) at ART start. At multivariable analysis, lower immune recovery (measured by change in CD4 from ART start at each time interval) was associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count of 101-200 cells/µL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, -26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median time to reach >400 cells/µL was longer in males (197.4 weeks, IQR:119.9-312.0), compared to females (144.7 weeks, IQR:96.6-219.7, P<0.001). The cumulative probability of attaining CD4 >400 cells/µL over 7 years was higher in females compared to males (P<0.001).

Conclusions: There was long-term, continuous, immunologic recovery up to 7 years after ART initiation in an urban Ugandan cohort. Virologically suppressed women had better sustained immune recovery than men. Men take longer to immune reconstitute and have a lower probability of reaching a CD4 cell count >400 cells/µL. The biologic mechanisms of these gender differences need further exploration.

Figure 1. Study flow diagram.

Figure 2. Median CD4 count over time stratified by baseline CD4 count.

The full line with diamonds represents people with baseline CD4 count ≤100 cells/µL. The long dash line with ‘x’ s represents people with baseline CD4 count 101-200 cells/µL. The long dash-dotted line with triangles represents people with baseline CD4 count >200 cells/µL.

Figure 3. Probability of achieving CD4 count >400 cells/µL and number at risk by baseline CD4 count.

The full line represents people with baseline CD4 count ≤100 cells/µL. The long dash line represents people with baseline CD4 count 101-200 cells/µL. The long dash-dotted line represents people with baseline CD4 count >200 cells/µL.

Figure 4. Probability of achieving CD4 count normalization (i.e. CD4 >400 cells/µL) and number at risk by gender.

The full line represents women. The long dash line represents men.

Figure 5. Median CD4 count trajectory stratified by gender within baseline CD4 count groups.

The full line represents women. The long dash line represents men.