Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study

Abstract

Introduction: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up.

Methods: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations.

Results: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%).

Conclusions: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.

Keywords: HIV treatment; HIV viraemia; Treat All; antiretroviral therapy; prospective cohort; sub-Saharan Africa.

FIGURE 1

Flow chart of inclusion into the analytic cohort from the Rakai Community Cohort Study (RCCS).

FIGURE 2

Sankey diagram of person‐level viral load trajectories among participants contributing three visits (two visit‐pairs) to the analytic cohort (N = 1524). Abbreviation: c/ml, HIV RNA copies/ml.

FIGURE 3

Conditional proportions of high‐ and low‐level HIV viraemia at follow‐up in the visit‐pair (N = 4604).

FIGURE 4

Weighted unadjusted and adjusted risk ratios of persistent high‐level viraemia (≥1000 copies/ml), relative to sustained or new low‐level viraemia or suppression, by calendar period—stratified by sex and community type. Notes: Risk ratios (RRs) and 95% confidence intervals (95% CI) were estimated from Poisson regression with generalized estimating equations, exchangeable covariance matrices, and robust standard errors. Error bars represent 95% CI for estimated risk ratios of persistent high‐level viraemia. Calendar period represents the survey interval in which a participant's index visit was observed (Oct. 2016–May 2018, referent: Feb. 2015–Sep. 2016). Sustained or new low‐level viraemia or suppression was defined as <1000 copies/ml across visits or at follow‐up only.

FIGURE 5

Weighted regional and community‐level prevalence of persistent high‐level viraemia (≥1000 copies/ml), by sex and calendar period. Notes: Error bars in panels A and B represent 95% confidence intervals (95% CI) for prevalence estimates of persistent high‐level viraemia. Bars in panel C represent the absolute difference in community‐level prevalence of persistent high‐level viraemia between survey rounds. Region names have been geomasked with letter identifiers.