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Previous studies demonstrated that individuals with subtype D HIV infection who had been infected for 2 or more years were frequently misclassified as assay positive using cross-sectional incidence assays. Samples from 510 subjects (212 subtype A, 298 subtype D) who were infected for 2.2 to 14.5 years (median 5.4 years) and were not virally suppressed were tested using an LAg-Avidity enzyme immunoassay (LAg-Avidity EIA), Bio-Rad Avidity assay, and BED capture enzyme immunoassay (BED-CEIA). The performance of these three assays was evaluated using various assay cutoff values [LAg-Avidity EIA: <1.0 OD-n and <2.0 OD-n; Bio-Rad Avidity assay: <40% avidity index (AI) and <80% AI; BED-CEIA: <0.8 OD-n]. The mean LAg-Avidity EIA result was higher for subtype A than D (4.54±0.95 vs. 3.86±1.26, p<0.001); the mean Bio-Rad Avidity assay result was higher for subtype A than D (88.9%±12.5% vs. 75.1±30.5, p<0.001); and the mean BED-CEIA result was similar for the two subtypes (2.2±1.2 OD-n for subtype A, 2.2±1.3 OD-n for subtype D, p<0.9). The frequency of misclassification was higher for individuals with subtype D infection compared to those with subtype A infection, using either the LAg-Avidity EIA with a cutoff of <2.0 OD-n or the Bio-Rad Avidity assay with cutoffs of <40% or <80% AI. No subtype-specific differences in assay performance were observed using the BED-CEIA. Sex and age were not significantly associated with misclassification by any assay. The LAg-Avidity EIA with a cutoff <1.0 OD-n had the lowest frequency of misclassification in this Ugandan population.

Introduction: Analysis of samples from Uganda using serologic HIV incidence assays reveal that individuals with subtype D infection often have weak humoral immune responses to HIV infection. It is unclear whether this reflects a poor initial response to infection or a waning antibody response later in infection., Materials and Methods: Samples (N = 2614) were obtained from 114 women aged 18-45 years in the Ugandan Genital Shedding and Disease Progression Study cohort (2001-2009; 82 subtype A, 32 subtype D; median 23 samples/women, range 3-41 samples, median follow-up of 6.6 years). Samples were analyzed using the BED capture immunoassay (cutoff, 0.8 OD-n) and the avidity assay (cutoff, 90% Avidity Index). Antibody maturation was assessed by having the BED capture enzyme immunoassay (BED-CEIA) or avidity value exceed the assay cutoff 1 or 2 years after infection. The waning antibody response was measured by having the BED-CEIA or avidity value fall >20% below the maximum value., Results: For the BED-CEIA, 8 women with subtype A infection and 3 women with subtype D infection never progressed previously the cutoff value (median, 5.9 years follow-up after infection). Six women with subtype D infection never achieved an avidity index >90%. Subtype did not impact the proportion of women whose assay values regressed by >20% of the maximal value (for BED-CEIA: 33% for A, 41% for D, P = 0.51; for avidity: 1% for A, 6% for D, P = 0.19)., Discussion: The higher frequency of misclassification of individuals with long-term subtype D infection as recently infected using serologic incidence assays reflects a weak initial antibody response to HIV infection that is sustained over time.

Background: The association between initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection and possible herpes simplex virus type 2 (HSV-2) shedding and genital ulcer disease (GUD) has not been evaluated., Methods: GUD and vaginal HSV-2 shedding were evaluated among women coinfected with HIV and HSV-2 (n = 440 for GUD and n = 96 for HSV-2 shedding) who began ART while enrolled in a placebo-controlled trial of HSV-2 suppression with acyclovir in Rakai, Uganda. Monthly vaginal swabs were tested for HSV-2 shedding, using a real-time quantitative polymerase chain reaction assay. Prevalence risk ratios (PRRs) of GUD were estimated using log binomial regression. Random effects logistic regression was used to estimate odds ratios (ORs) of HSV-2 shedding., Results: Compared with pre-ART values, GUD prevalence increased significantly within the first 3 months after ART initiation (adjusted PRR, 1.94; 95% confidence interval [CI], 1.04-3.62) and returned to baseline after 6 months of ART (adjusted PRR, 0.80; 95% CI, .35-1.80). Detection of HSV-2 shedding was highest in the first 3 months after ART initiation (adjusted OR, 2.58; 95% CI, 1.48-4.49). HSV-2 shedding was significantly less common among women receiving acyclovir (adjusted OR, 0.13; 95% CI, .04-.41)., Conclusions: The prevalence of HSV-2 shedding and GUD increased significantly after ART initiation, possibly because of immune reconstitution inflammatory syndrome. Acyclovir significantly reduced both GUD and HSV-2 shedding and should be considered to mitigate these effects following ART initiation.