Altered Antibody Responses in Persons Infected with HIV-1 While Using Preexposure Prophylaxis

Abstract

Preexposure prophylaxis (PrEP) is an effective HIV prevention tool, although effectiveness is dependent upon adherence. It is important to characterize the impact of PrEP on HIV antibody responses in people who experience breakthrough infections to understand the potential impact on timely diagnosis and treatment. Longitudinal HIV-1-specific antibody responses were evaluated in 42 people who inject drugs (PWID) from the Bangkok Tenofovir Study (BTS) (placebo = 28; PrEP = 14) who acquired HIV while receiving PrEP. HIV-1 antibody levels and avidity to three envelope proteins (gp41, gp160, and gp120) were measured in the plasma using a customized Bio-Plex (Bio-Rad Laboratories, Hercules, CA) assay. A time-to-event analysis was performed for each biomarker to compare the distribution of times at which study subjects exceeded the recent/long-term assay threshold, comparing PrEP and placebo treatment groups. We fit mixed-effects models to identify longitudinal differences in antibody levels and avidity between groups. Overall, longitudinal antibody levels and avidity were notably lower in the PrEP breakthrough group compared to the placebo group. Time-to-event analyses demonstrated a difference in time to antibody reactivity between treatment groups for all Bio-Plex biomarkers. Longitudinal gp120 antibody levels within the PrEP breakthrough group were decreased compared to the placebo group. When accounting for PrEP adherence, both gp120 and gp160 antibody levels were lower in the PrEP breakthrough group compared to the placebo group. We demonstrate hindered envelope antibody maturation in PWID who became infected while receiving PrEP in the BTS, which has significant implications for HIV diagnosis. Delayed maturation of the antibody response to HIV may increase the time to detection for antibody-based tests. Clinical Trial Registration Number, NCT00119106.

Keywords: HIV; antibody maturation; preexposure prophylaxis; seroconversion.

Conflict of interest statement

J.G.G-L is named in U.S. Government patents on “Inhibition of HIV infection through chemoprophylaxis”, and in U.S. Government patent applications on “HIV postexposure prophylaxis” and “HIV pre-exposure prophylaxis”. The other authors declare no conflicts of interest.

Figures

FIG. 1.

Survival analysis comparing the distribution of times, at which study subjects exceeded the recent/long-term assay threshold between PrEP and placebo treatment groups. Product limit survival estimates for gp120 and gp160 antibody levels (A), and for gp120, gp160, and gp41 antibody avidity (B) by time after viral RNA positivity. The PrEP and untreated control group are displayed in solid red and blue lines, respectively, with 95% confidence intervals shaded. -a, avidity; -n, normalized value; PrEP, preexposure prophylaxis.

FIG. 2.

Longitudinal HIV-1 envelope antibody responses among BTS participants. Antibody levels (A) and avidity index values (B) for each individual subject are plotted for the PrEP treatment (red lines) and untreated control (blue lines) groups for gp120, gp160, and gp41. LOESS curves for the PrEP and untreated control group are displayed as bold red and blue lines, respectively. BTS, Bangkok Tenofovir Study; LOESS, locally estimated scatterplot smoothing.