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BackgroundVRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed.Methods and findingsHIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18–50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits.ConclusionsVRC01 administe...

Objective US guidelines recommend at least annual HIV testing for those at risk. This analysis assessed frequency and correlates of infrequent HIV testing and late diagnosis among black men who have sex with men (BMSM). Methods HIV testing history was collected at enrollment from participants in HPTN 061, an HIV prevention trial for at-risk US BMSM. Two definitions of late HIV diagnosis were assessed: CD4 cell count <200 cells/mm3 or <350 cells/mm3 at diagnosis. Results HPTN 061 enrolled 1553 BMSM. HIV testing questions were completed at enrollment by 1284 (98.7%) of 1301 participants with no prior HIV diagnosis; 272 (21.2%) reported no HIV test in prior 12 months (infrequent testing); 155 of whom (12.1% of the 1284 with testing data) reported never testing. Infrequent HIV testing was associated with: not seeing a medical provider in the prior 6 months (relative risk [RR]: 1.08, 95% confidence intervals [CI]: 1.03–1.13), being unemployed (RR 1.04, CI: 1.01–1.07), and having high internalized HIV stigma (RR: 1.03, CI: 1.0–1.05). New HIV diagnoses were more likely among infrequent testers compared to men tested in the prior year (18.4% vs. 4.4%; OR: 4.8, 95% CI: 3.2–7.4). Among men with newly diagnosed HIV, 33 (39.3%) had a CD4 cell count <350 cells/mm;3 including 17 (20.2%) with CD4 <200 cells/mm.3 Conclusions Infrequent HIV testing, undiagnosed infection, and late diagnosis were common among BMSM in this study. New HIV diagnoses were more common among infrequent testers, underscoring the need for additional HIV testing and prevention efforts among US BMSM.

Summary Background Bioinformatically designed mosaic antigens increase the breadth of HIV vaccine-elicited immunity. This study compared the safety, tolerability, and immunogenicity of a newly developed, tetravalent Ad26 vaccine with the previously tested trivalent formulation. Methods This randomised, parallel-group, placebo-controlled, double-blind, phase 1/2a study (TRAVERSE) was done at 11 centres in the USA and one centre in Rwanda. Eligible participants were adults aged 18 to 50 years, who were HIV-uninfected, healthy at screening based on their medical history and a physical examination including laboratory assessment and vital sign measurements, and at low risk of HIV infection in the opinion of study staff, who applied a uniform definition of low-risk guidelines that was aligned across sites. Enrolled participants were randomly assigned at a 2:1 ratio to tetravalent and trivalent groups. Participants in tetravalent and trivalent groups were then further randomly assigned at a 5:1 ratio to adenovirus 26 (Ad26)-vectored vaccine and placebo subgroups. Randomisation was stratified by region (USA and Rwanda) and based on a computer-generated schedule using randomly permuted blocks prepared under the sponsor's supervision. We masked participants and investigators to treatment allocation throughout the study. On day 0, participants received a first injection of tetravalent vaccine (Ad26.Mos4.HIV or placebo) or trivalent vaccine (Ad26.Mos.HIV or placebo), and those injections were repeated 12 weeks later. At week 24, vaccine groups received a third dose of tetravalent or trivalent together with clade C gp140, and this was repeated at week 48, with placebos again administered to the placebo group. All study vaccines and placebo were administered by intramuscular injection in the deltoid muscle. We assessed adverse events in all participants who received at least one study injection (full analysis set) and Env-specific binding antibodies in all participants who received at least the first three vaccinations according to the protocol-specified vaccination schedule, had at least one measured post-dose blood sample collected, and were not diagnosed with HIV during the study (per-protocol set). This study is registered with Clinicaltrials.gov , NCT02788045 . Findings Of 201 participants who were enrolled and randomly assigned, 198 received the first vaccination: 110 were in the tetravalent group, 55 in the trivalent group, and 33 in the placebo group. Overall, 185 (93%) completed two scheduled vaccinations per protocol, 180 (91%) completed three, and 164 (83%) completed four. Solicited, self-limiting local, systemic reactogenicity and unsolicited adverse events were similar in vaccine groups and higher than in placebo groups. All participants in the per-protocol set developed clade C Env binding antibodies after the second vaccination, with higher total IgG titres after the tetr...

Understanding what social factors are associated with risk of HIV acquisition and transmission among gay, bisexual and other men who have sex with men (MSM) is a critical public health goal. Experiencing discrimination may increase risk of HIV infection among MSM. This analysis assessed relations between experiences of sexual orientation- and race-based discrimination and sexual HIV risk behavior among MSM in New York City. 1,369 MSM completed a self-administered computerized assessment of past 3-month sexual behavior, experience of social discrimination and other covariates. Regression models assessed relations between recent experience of discrimination and sexual HIV risk behavior. Mean age was 32 years; 32 % were white; 32 % Latino/Hispanic; 25 % African American/Black. Of MSM who self-reported HIV-positive or unknown status (377), 7 % (N = 27) reported having unprotected insertive anal intercourse with an HIV-negative or unknown status partner (“HIV transmission risk”). Of MSM who self-reported HIV-negative status (992), 11 % (110) reported unprotected receptive anal intercourse with an HIV-positive or unknown status partner (“HIV acquisition risk”). HIV acquisition risk was positively associated with sexual orientation-based discrimination in home or social neighborhoods, but not race-based discrimination. We observed that sexual orientation-based discrimination was associated with sexual HIV risk behavior among urban-dwelling MSM. Addressing environmental sources of this form of discrimination, as well as the psychological distress that may result, should be prioritized in HIV prevention efforts.