Dataset Information

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.

ABSTRACT:

Background

The foreskin is the site of most HIV acquisition in uncircumcised heterosexual men. Although HIV-exposed, seronegative (HESN) uncircumcised men demonstrate HIV-neutralizing IgA and increased antimicrobial peptides (AMPs) in the foreskin prepuce, no prospective studies have examined the mucosal immune correlates of HIV acquisition.

Methods

To assess the association of foreskin immune parameters with HIV acquisition, antimicrobial peptides and IgA with the capacity to neutralize a primary clade C HIV strain were quantified by blinded investigators, using sub-preputial swabs collected longitudinally during a randomized trial of male circumcision for HIV prevention in Rakai, Uganda.

Results

Participants were 99 men who acquired HIV (cases) and 109 randomly selected controls who remained HIV seronegative. At enrollment, 44.4% of cases vs. 69.7% of controls demonstrated IgA neutralization (adjusted OR?=?0.31; 95% CI, 0.16-0.61). IgA neutralization was detected in 38.7% of cases and 70.7% of controls at the last seronegative case visit prior to HIV acquisition and the comparable control visit (adjusted OR 0.21; 95% CI, 0.11-0.39). Levels of the ?-defensins and secretory leukocyte protease inhibitor (SLPI) were over ten-fold higher in the foreskin prepuce of cases who acquired HIV, both at enrollment (mean 4.43 vs. 3.03 and 5.98 vs. 4.61 log(n) pg/mL, P?=?0.005 and 0.009, respectively), and at the last seronegative visit (mean 4.81 vs. 3.15 and 6.46 vs. 5.20 log(n) pg/mL, P?=?0.0002 and 0.013).

Conclusions

This prospective, blinded analysis is the first to assess the immune correlates of HIV acquisition in the foreskin. HIV-neutralizing IgA, previously associated with the HESN phenotype, was a biomarker of HIV protection, but other HESN associations correlated with increased HIV acquisition. This emphasizes the importance of prospective epidemiological studies or in vitro tissue studies to define the impact of mucosal parameters on HIV risk.

SUBMITTER: Hirbod T

PROVIDER: S-EPMC4183701 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.

Hirbod Taha T Kong Xiangrong X Kigozi Godgrey G Ndyanabo Anthony A Serwadda David D Prodger Jessica L JL Tobian Aaron A AA Nalugoda Fred F Wawer Maria J MJ Shahabi Kamnoosh K Rojas Olga L OL Gommerman Jennifer L JL Broliden Kristina K Kaul Rupert R Gray Ronald H RH

PLoS pathogens 20141002 10

<h4>Background</h4>The foreskin is the site of most HIV acquisition in uncircumcised heterosexual men. Although HIV-exposed, seronegative (HESN) uncircumcised men demonstrate HIV-neutralizing IgA and increased antimicrobial peptides (AMPs) in the foreskin prepuce, no prospective studies have examined the mucosal immune correlates of HIV acquisition.<h4>Methods</h4>To assess the association of foreskin immune parameters with HIV acquisition, antimicrobial peptides and IgA with the capacity to neu ...[more]

PMID: 25275513

Similar Datasets

Project description:BackgroundAlthough efficacy is unknown, many men who have sex with men (MSM) attempt to reduce HIV risk by adapting condom use, partner selection, or sexual position to the partner's HIV serostatus. We assessed the association of seroadaptive practices with HIV acquisition.Methodology/principal findingsWe pooled data on North American MSM from four longitudinal HIV-prevention studies. Sexual behaviors reported during each six-month interval were assigned sequentially to one of six mutually exclusive risk categories: (1) no unprotected anal intercourse (UAI), (2) having a single negative partner, (3) being an exclusive top (only insertive anal sex), (4) serosorting (multiple partners, all HIV negative), (5) seropositioning (only insertive anal sex with potentially discordant partners), and (6) UAI with no seroadaptive practices. HIV antibody testing was conducted at the end of each interval. We used Cox models to evaluate the independent association of each category with HIV acquisition, controlling for number of partners, age, race, drug use, and intervention assignment. 12,277 participants contributed to 60,162 six-month intervals with 663 HIV seroconversions. No UAI was reported in 47.4% of intervals, UAI with some seroadaptive practices in 31.8%, and UAI with no seroadaptive practices in 20.4%. All seroadaptive practices were associated with a lower risk, compared to UAI with no seroadaptive practices. However, compared to no UAI, serosorting carried twice the risk (HR?=?2.03, 95%CI:1.51-2.73), whereas seropositioning was similar in risk (HR?=?0.85, 95%CI:0.50-1.44), and UAI with a single negative partner and as an exclusive top were both associated with a lower risk (HR?=?0.56, 95%CI:0.32-0.96 and HR?=?0.55, 95%CI:0.36-0.84, respectively).Conclusions/significanceSeroadaptive practices appear protective when compared with UAI with no seroadaptive practices, but serosorting appears to be twice as risky as no UAI. Condom use and limiting number of partners should be advocated as first-line prevention strategies, but seroadaptive practices may be considered harm-reduction for men at greatest risk.

Project description:BackgroundWhether a broadly neutralizing antibody (bnAb) can be used to prevent human immunodeficiency virus type 1 (HIV-1) acquisition is unclear.MethodsWe enrolled at-risk cisgender men and transgender persons in the Americas and Europe in the HVTN 704/HPTN 085 trial and at-risk women in sub-Saharan Africa in the HVTN 703/HPTN 081 trial. Participants were randomly assigned to receive, every 8 weeks, infusions of a bnAb (VRC01) at a dose of either 10 or 30 mg per kilogram (low-dose group and high-dose group, respectively) or placebo, for 10 infusions in total. HIV-1 testing was performed every 4 weeks. The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay.ResultsAdverse events were similar in number and severity among the treatment groups within each trial. Among the 2699 participants in HVTN 704/HPTN 085, HIV-1 infection occurred in 32 in the low-dose group, 28 in the high-dose group, and 38 in the placebo group. Among the 1924 participants in HVTN 703/HPTN 081, infection occurred in 28 in the low-dose group, 19 in the high-dose group, and 29 in the placebo group. The incidence of HIV-1 infection per 100 person-years in HVTN 704/HPTN 085 was 2.35 in the pooled VRC01 groups and 2.98 in the placebo group (estimated prevention efficacy, 26.6%; 95% confidence interval [CI], -11.7 to 51.8; P = 0.15), and the incidence per 100 person-years in HVTN 703/HPTN 081 was 2.49 in the pooled VRC01 groups and 3.10 in the placebo group (estimated prevention efficacy, 8.8%; 95% CI, -45.1 to 42.6; P = 0.70). In prespecified analyses pooling data across the trials, the incidence of infection with VRC01-sensitive isolates (IC80 <1 μg per milliliter) per 100 person-years was 0.20 among VRC01 recipients and 0.86 among placebo recipients (estimated prevention efficacy, 75.4%; 95% CI, 45.5 to 88.9). The prevention efficacy against sensitive isolates was similar for each VRC01 dose and trial; VRC01 did not prevent acquisition of other HIV-1 isolates.ConclusionsVRC01 did not prevent overall HIV-1 acquisition more effectively than placebo, but analyses of VRC01-sensitive HIV-1 isolates provided proof-of-concept that bnAb prophylaxis can be effective. (Supported by the National Institute of Allergy and Infectious Diseases; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 ClinicalTrials.gov numbers, NCT02716675 and NCT02568215.).

Dataset Information

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.

Background

Methods

Results

Conclusions

Publications

HIV acquisition is associated with increased antimicrobial peptides and reduced HIV neutralizing IgA in the foreskin prepuce of uncircumcised men.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets