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      Sexually transmitted infections amongst men who have sex with men (MSM) in South Africa

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          Abstract

          There is limited data about bacterial STIs in MSM populations in sub-Saharan Africa. Our retrospective analysis used data from the HVTN 702 HIV vaccine clinical trial (October 2016 to July 2021). We evaluated multiple variables. Polymerase chain reaction testing was conducted on urine and rectal samples to detect Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) every 6 months. Syphilis serology was conducted at month 0 and thereafter every 12 months. We calculated STI prevalence and the associated 95% confidence intervals until 24 months of follow-up. The trial enrolled 183 participants who identified as male or transgender female, and of homosexual or bisexual orientation. Of these, 173 had STI testing done at month 0, median age was 23 (IQR 20–25) years, with median 20.5 (IQR 17.5–24.8) months follow-up (FU). The clinical trial also enrolled and performed month 0 STI testing on 3389 female participants, median age 23 (IQR 21–27) years, median 24.8 (IQR 18.8–24.8) months FU and 1080 non-MSM males with a median age of 27 (IQR 24–31) years, median 24.8 (IQR 23–24.8) months FU. At month 0, CT prevalence was similar in MSM and females (26.0% vs 23.0%, p = 0.492) but was more prevalent in MSM compared to non-MSM males (26.0% vs 14.3%, p = 0.001). CT was the most prevalent STI among MSM at months 0 and 6 but declined from month 0 to month 6 (26.0% vs 17.1%, p = 0.023). In contrast, NG did not decline in MSM between months 0 and 6 (8.1% vs 7.1%, p = 0.680) nor did syphilis prevalence between months 0 and 12 (5.2% vs 3.8%, p = 0.588). Bacterial STI burden is higher in MSM compared to non-MSM males, and CT is the most prevalent bacterial STI amongst MSM. Preventive STI vaccines, especially against CT, may be helpful to develop.

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          Most cited references23

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          Approximate Is Better than "Exact" for Interval Estimation of Binomial Proportions

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            Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial.

            Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels. We undertook a double-blind, phase II, test-of-concept study at 34 sites in North America, the Caribbean, South America, and Australia. We randomly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506). Randomisation was prestratified by sex, adenovirus type 5 (Ad5) antibody titre at baseline, and study site. Primary objective was a reduction in HIV-1 acquisition rates (tested every 6 months) or a decrease in HIV-1 viral-load setpoint (early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis). Analyses were per protocol and modified intention to treat. The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis. This study is registered with ClinicalTrials.gov, number NCT00095576. In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1.2 [95% CI 0.6-2.2]). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4.61 vs 4.41 log(10) copies per mL, one tailed p value for potential benefit 0.66). The vaccine elicited interferon-gamma ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n=354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2.3 [95% CI 1.2-4.3]) and uncircumcised men (3.8 [1.5-9.3]), but was not increased in Ad5 seronegative (1.0 [0.5-1.9]) or circumcised (1.0 [0.6-1.7]) men. This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level. Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored.
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              Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120/MF59 in Adults

              BACKGROUND A safe, effective vaccine is essential to end HIV. A canarypox/protein HIV vaccine regimen showed modest efficacy at reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus demonstrated potent humoral and cellular responses in a Phase 1/2a trial and triggered a Phase 2b/3 double-blinded trial to assess the safety and efficacy of this regimen in South Africa. METHODS We enrolled and randomized 5,404 healthy, HIV-uninfected 18-35-year olds at 14 sites to vaccine (2,704 participants) or placebo (2,700 participants) between 26 October 2016 and 21 June 2019. The vaccine regimen consisted of two ALVAC-HIV (vCP2438) (expressing HIV-1 subtype C env, clade B gp41, gag and pro) immunizations at months 0 and 1, with booster immunizations of ALVAC-HIV plus bivalent subtype C gp120 protein/MF59 adjuvant at months 3, 6, 12 and 18. Efficacy was evaluated by HIV testing every 3 months. RESULTS In January 2020, pre-specified non-efficacy criteria were met at an interim analysis; further vaccinations were subsequently halted. The vaccines were safe and well-tolerated in the study population (median age 24, 70% female-sex-at-birth). Over the primary 24-month follow-up, there were 133 infections among placebo recipients and 138 among vaccinees (hazard ratio = 1.02; 95%CI, 0.81-1.30; P=0.84). Pre-specified subgroup analyses demonstrated no difference in efficacy by sex or when restricting to follow-up post-4th vaccination, and no difference amongst female-sex-at-birth by age, BMI, prevalent STIs, behavioral risk score or region. CONCLUSIONS The ALVAC/gp120 regimen did not prevent HIV infection in South Africans despite prior evidence of immunogenicity. ClinicalTrials.gov (NCT02968849)

                Author and article information

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                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLOS Glob Public Health
                PLOS Glob Public Health
                plos
                PLOS Global Public Health
                Public Library of Science (San Francisco, CA USA )
                2767-3375
                5 April 2023
                2023
                : 3
                : 4
                : e0001782
                Affiliations
                [1 ] Faculty of Health Sciences, Perinatal HIV Research Unit, University of the Witwatersrand, Diepkloof, Soweto, South Africa
                [2 ] Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, United States of America
                [3 ] Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Vaccine Research Program, Bethesda, Maryland, United States of America
                [4 ] Desmond Tutu HIV Foundation, University of Cape Town, Cape Town, South Africa
                [5 ] Fred Hutchinson Cancer Center (SCHARP, HVTN), Seattle, WA, United States of America
                [6 ] Synergy Biomed Research Institute, East London, South Africa
                [7 ] Sefako Makgatho Health Sciences University/NHLS, Ga-Rankuwa, South Africa
                National University of Singapore, SINGAPORE
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-0435-1292
                https://orcid.org/0000-0001-8701-2001
                https://orcid.org/0000-0002-4965-0624
                https://orcid.org/0000-0003-4385-8915
                https://orcid.org/0000-0001-5231-9951
                Article
                PGPH-D-22-00629
                10.1371/journal.pgph.0001782
                10075439
                37018240
                d8248693-1b76-402d-9b66-24b5c86369b8
                © 2023 Mashingaidze et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 April 2022
                : 7 March 2023
                Page count
                Figures: 1, Tables: 4, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                People and Places
                Population Groupings
                Sexuality Groupings
                Men WHO Have Sex with Men
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Syphilis
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Sexually Transmitted Diseases
                Syphilis
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Bacterial Diseases
                Treponematoses
                Syphilis
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Treponematoses
                Syphilis
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                Sexually Transmitted Diseases
                Biology and Life Sciences
                Anatomy
                Digestive System
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                Custom metadata
                All data underlying the findings reported in this manuscript are available at: https://atlas.scharp.org/cpas/project/HVTN%20Public%20Data/HVTN%20702/begin.view?, in a folder named Mashingaidze et al. PLOS Global Public Health 2023.

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