HIV-1 Nucleic Acids Identify Rectal HIV Exposures in Self-Collected Rectal Swabs, Whereas Y-Chromosome Single Tandem Repeat Mixtures Are Not Reliable Biomarkers of Condomless Receptive Anal Intercourse.

BACKGROUND: To focus interventions, biomarkers of HIV-1 exposure could help in identifying subpopulations at highest risk of acquisition. We assessed whether Y-chromosome single tandem repeat (YSTR) mixtures obtained from rectal swabs could serve as a biomarker of condomless receptive anal intercourse (CRAI) among men who have sex with men and transgender women and evaluated the feasibility of detecting HIV-1 virions to assess exposures. METHODS: Twenty-nine sexually active HIV-seronegative men who have sex with men and one transgender woman from New York City answered on-site and mobile app sexual behavior questionnaires. They were randomized to collecting self-administered rectal swabs every morning or after receptive anal intercourse (RAI). YSTR profiles were assessed from blood sample and swabs; HIV-1 exposure was measured by conducting quantitative polymerase chain reaction in swabs. RESULTS: After 2 months, the daily mobile survey had 135%-201% more instances of anal sex acts and 170%-193% more RAI than on-site surveys. Daily mobile reporting had 11%-35% less CRAI events than those reported on-site (Pdaily = 0.001; Pper-sex = 0.047). The daily swabbing arm reported less RAI (P < 0.001) and CRAI (P < 0.038) and had 2.95 lower odds of detecting YSTR mixtures (P = 0.021) than the per-sex-event arm. Surprisingly, YSTR detection was not significantly modified by report of bowel movements and lubricant, enema, or condom use. No participant became HIV-1 infected, yet HIV-1 total nucleic acids were detected in 6 independent episodes of CRAI in 2 participants taking pre-exposure prophylaxis. CONCLUSIONS: YSTR mixtures demonstrated 80% specificity but only 30% sensitivity as a biomarker of CRAI in self-collected rectal swabs. However, detection of HIV-1 exposures in self-collected swabs may help in identifying those needing further HIV risk reduction strategies.

Herpes Simplex Virus Suppressive Therapy in Herpes Simplex Virus-2/Human Immunodeficiency Virus-1 Coinfected Women Is Associated With Reduced Systemic CXCL10 But Not Genital Cytokines.

BACKGROUND: Herpes simplex virus type-2 (HSV-2) may heighten immune activation and increase human immunodeficiency virus 1 (HIV-1) replication, resulting in greater infectivity and faster HIV-1 disease progression. An 18-week randomized, placebo-controlled crossover trial of 500 mg valacyclovir twice daily in 20 antiretroviral-naive women coinfected with HSV-2 and HIV-1 was conducted and HSV-2 suppression was found to significantly reduce both HSV-2 and HIV-1 viral loads both systemically and the endocervical compartment. METHODS: To determine the effect of HSV-2 suppression on systemic and genital mucosal inflammation, plasma specimens, and endocervical swabs were collected weekly from volunteers in the trial and cryopreserved. Plasma was assessed for concentrations of 31 cytokines and chemokines; endocervical fluid was eluted from swabs and assayed for 14 cytokines and chemokines. RESULTS: Valacyclovir significantly reduced plasma CXCL10 but did not significantly alter other cytokine concentrations in either compartment. CONCLUSIONS: These data suggest genital tract inflammation in women persists despite HSV-2 suppression, supporting the lack of effect on transmission seen in large scale efficacy trials. Alternative therapies are needed to reduce persistent mucosal inflammation that may enhance transmission of HSV-2 and HIV-1.

High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.

BACKGROUND: In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants). RESULTS: Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001). CONCLUSIONS: High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.