Use of a multifaceted approach to analyze HIV incidence in a cohort study of women in the United States: HIV Prevention Trials Network 064 Study

Abstract

Background: Reliable methods for estimating the incidence of human immunodeficiency virus (HIV) infection are needed to monitor the epidemic, identify at-risk populations, and evaluate HIV prevention strategies. We used a multifaceted approach to estimate HIV incidence in the HIV Prevention Trials Network (HPTN) 064 study.

Methods: The HPTN 064 study enrolled 2067 HIV-seronegative women and 32 HIV-seropositive women with no prior HIV infection diagnosis. Women were followed for up to 12 months. HIV incidence estimates were based on (1) detection of acute HIV infection, (2) documentation of HIV seroconversion, and (3) detection of recent HIV infection, using a multiassay algorithm (MAA).

Results: Two women had acute HIV infection at enrollment, 4 seroconverted, and 2 were identified as recently infected at enrollment using the MAA. The annual HIV incidence estimate based on acute infection at enrollment (2.52% [95% confidence interval {CI}, .17%-9.33%], using a 14-day window period) was higher than the estimate based on seroconversion (0.24% [95% CI, .07%-.62%]; P = .027). Incidence estimates obtained using the MAA at enrollment and at the end of study were 0.25% (95% CI, .03%-.93%) and 0.13% (95% CI, .006%-.76%), respectively.

Conclusions: We detected a high frequency of acute infection at enrollment. Cross-sectional HIV incidence estimates obtained using the MAA were similar to the longitudinal estimate based on HIV seroconversion.

Clinical trials registration: NCT00995176.

Figure 1.

BED capture enzyme immunoassay (BED-CEIA) and avidity test results. The plots show results from the BED-CEIA (normalized optical density units [OD-n]) and the avidity assay (avidity index, %) for women at different study visits (plotted as days after enrollment). A, Results for 2 women (subjects 7 and 8) who received a new diagnosis of human immunodeficiency virus (HIV) infection at the time of study enrollment and were identified as recently infected at enrollment using the multiassay algorithm (MAA; Table 2). B, Results for five women who seroconverted during the study, of whom 1 (subject 1) had acute infection at study entry and 4 (subjects 3–6) were HIV uninfected at study entry (Table 2). C, Results for 30 women who received a new diagnosis of HIV infection at the time of study enrollment and were identified by the MAA as not recently infected at enrollment. The dashed lines indicate the cutoffs for the standard BED-CEIA (<0.8 OD-n) and the standard avidity assay (<40%); higher cutoffs are used in the MAA for both assays (<1.0 for the BED-CEIA and <80% for the avidity assay). Note that 2 women had BED-CEIA results that decreased over time; in both cases, the values remained greater than the cutoff for the standard BED-CEIA (>0.8 OD-n) and greater than the cutoff that is used in the MAA for the BED-CEIA (>1.0 OD-n). Both of those women had high HIV loads at all visits tested (range, 25 810 to >10 000 copies/mL). One of the women had a very low CD4⁺ T-cell count at study enrollment (11 cells/µL), which could have explained the decline in her serologic response to HIV infection over time, as measured by the BED-CEIA.