A combination of the Limiting-Antigen Avidity Assay (LAg-Avidity) with viral load (VL) >1000 copies/mL is being used internationally for cross-sectional estimation of population-level HIV incidence. However, the capacity of this method to measure a point estimate and a change in incidence over time has not been validated in an East African setting where HIV-1 subtypes A and D circulate.
We analyzed longitudinal data for two time periods in the Rakai Community Cohort Study (RCCS) in Uganda. Between survey Rounds 12 and 13 (2006-2007 and 2008-2009) the observed incidence was 1.05/100 person years (95% CI 0.90, 1.23). Between Rounds 14 and 15 (2010-2011 and 2012-2013) the observed incidence was significantly lower, 0.66/100 person years (95% CI 0.52, 0.83), P<0.05. The performance of the current LAg-Avidity protocol, with mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0% was compared to a subtype specific MMDRI and FRR calibrated by survey round.
Based on gp41 sequence data, the subtype proportion in the RCCS was 45% A and 55% D, and the subtype adjusted MDRI was 184 days. In Round 13 there were 9,973 subjects, of whom 1244 were HIV-positive, with 422 were on ART. Of the 742/822 remaining subjects with samples available for testing, 49 were classified as recent and the FRR was 1.1% (6/544). In Round 15 there were 6749 subjects, of whom were 985 HIV-positive, with 423 were on ART. Of the 500/562 remaining subjects with samples available for testing, 52 were classified as recent and the FRR was 4.8% (16/332). Per protocol cross-sectional R13 incidence was 1.63 (95% CI 0.97, 2.30), and the R15 estimate was 2.55 (95% CI 1.51, 3.59), P<0.05. Both per protocol estimates exceeded the observed incidence. When using the MDRI adjusted for subtype and a round specific FRR the incidence estimates was 0.88% (95%CI 0.44, 1.33) for R13 and 0.67% (95% CI 0.00, 1.68) for R15, P=0.54, which were closer to the observed incidence.
In this subtype A/D epidemic, the per protocol methods of LAg-Avidity +VL over estimated observed incidence and failed to detect the decline in incidence between the two time periods. In contrast, when the method was adjusted by survey-specific FRR and an MDRI calibrated for the population’s subtype distribution, the HIV incidence estimates were similar to observed incidence and detected declines in incidence.