Clinical factors and outcomes associated with immune non-response among virally suppressed adults with HIV from Africa and the United States

Abstract

A significant minority of people living with HIV (PLWH) achieve viral suppression (VS) on antiretroviral therapy (ART) but do not regain healthy CD4 counts. Clinical factors affecting this immune non-response (INR) and its effect on incident serious non-AIDS events (SNAEs) have been challenging to understand due to confounders that are difficult to control in many study settings. The U.S. Military HIV Natural History Study (NHS) and African Cohort Study (AFRICOS). PLWH with sustained VS (< 400 copies/ml for at least two years) were evaluated for INR (CD4 < 350 cells/µl at the time of sustained VS). Logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for factors associated with INR. Cox proportional hazards regression produced adjusted hazard ratios (aHRs) for factors associated with incident SNAE after sustained VS. INR prevalence was 10.8% and 25.8% in NHS and AFRICOS, respectively. Higher CD4 nadir was associated with decreased odds of INR (aOR = 0.34 [95% CI 0.29, 0.40] and aOR = 0.48 [95% CI 0.40, 0.57] per 100 cells/µl in NHS and AFRICOS, respectively). After adjustment, INR was associated with a 61% increase in relative risk of SNAE [95% CI 1.12, 2.33]. Probability of "SNAE-free" survival at 15 years since sustained VS was approximately 20% lower comparing those with and without INR; nearly equal to the differences observed by 15-year age groups. CD4 monitoring before and after VS is achieved can help identify PLWH at risk for INR. INR may be a useful clinical indicator of future risk for SNAEs.

Figure 1

Time-to-incident SNAE. The first panel illustrates the difference in time-to-SNAE by INR status, with the blue representing CD4 ≥ 350 cells/µl and red representing CD4 < 350 cells/µl at viral suppression. The second panel illustrates the difference by age, with red representing < 35, blue representing 35–50 and green representing ≥ 50 years at ART initiation. The third panel represents the difference by nadir CD4, with blue representing < 350 cells/µl and red representing ≥ 350 cells/µl. The probability of “SNAE-free” survival 15 years after viral suppression was approximately 20% lower comparing those with and without INR; nearly equal to the difference observed by 15-year age groups.