Men who have sex with men (MSM) are disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. Previous reviews investigating the role of circumcision in preventing HIV and other STIs among MSM were inconclusive. Many new studies have emerged in the past decade. To inform global prevention strategies for HIV and other STIs among MSM, we reviewed all available evidence on the associations between circumcision and HIV and other STIs among MSM. In this systematic review and meta-analysis, we searched PubMed, Web of Science, BioMed Central, Scopus, ResearchGate, Cochrane Library, Embase, PsycINFO, Google Scholar, and websites of international HIV and STI conferences for studies published before March 8, 2018. Interventional or observational studies containing original quantitative data describing associations between circumcision and incident or prevalent infection of HIV and other STIs among MSM were included. Studies were excluded if MSM could not be distinguished from men who have sex with women only. We calculated pooled odds ratios (ORs) and their 95% CIs using random-effect models. We assessed risk of bias using the Newcastle-Ottawa scale. We identified 62 observational studies including 119 248 MSM. Circumcision was associated with 23% reduced odds of HIV infection among MSM overall (OR 0·77, 95% CI 0·67-0·89; number of estimates [k]=45; heterogeneity I2=77%). Circumcision was protective against HIV infection among MSM in countries of low and middle income (0·58, 0·41-0·83; k=23; I2=77%) but not among MSM in high-income countries (0·99, 0·90-1·09; k=20; I2=40%). Circumcision was associated with reduced odds of herpes simplex virus (HSV) infection among MSM overall (0·84, 0·75-0·95; k=5; I2=0%) and penile human papillomavirus (HPV) infection among HIV-infected MSM (0·71, 0·51-0·99; k=3; I2=0%). We found evidence that circumcision is likely to protect MSM from HIV infection, particularly in countries of low and middle income. Circumcision might also protect MSM from HSV and penile HPV infection. MSM should be included in campaigns promoting circumcision among men in countries of low and middle income. In view of the substantial proportion of MSM in countries of low and middle income who also have sex with women, well designed longitudinal studies differentiating MSM only and bisexual men are needed to clarify the effect of circumcision on male-to-male transmission of HIV and other STIs. National Natural Science Foundation of China, National Science and Technology Major Project of China, Australian National Health and Medical Research Council Early Career Fellowship, Sanming Project of Medicine in Shenzhen, National Institutes of Health, Mega Projects of National Science Research for the 13th Five-Year Plan, Doris Duke Charitable Foundation.

Background: Cross-sectional studies have found a high prevalence of syphilis and HIV infection among men who have sex with men (MSM) in China. Methods: A total of 218 HIV-negative MSM participated in this prospective cohort study. Interviewer-administered questionnaires were completed, and blood samples were obtained for HIV and syphilis testing, both upon enrollment and at 12-month follow-up. Results: Of enrolled participants, 56% (122) were retained for the full 12-month follow-up period. The cohort had an HIV incidence density of 5.4 (95% CI: 2.0–11.3)/100 person-year (PY) and a syphilis incidence density of 38.5(95% CI: 27.7–50.2)/100 PY. Having syphilis (odds ratio [OR]: 11.4, 95% CI: 1.2–104.7) and more than 5 male sexual partners within the past 12 months (OR: 6.5, 95% CI: 1.1–39.8) were independent risk factors for HIV seroconversion (each P < 0.05). Being married (OR: 3.5, 95% CI: 1.4–8.2) and having more than 5 male sexual partners within the past 12 months (OR: 4.7, 95% CI: 2.0–6.2) were risk factors for syphilis seroconversion, while age ≥30 (OR 2.1, 95% CI 0.7–9.5) and having recently engaged in unprotected receptive anal sex (OR: 2.4, 95% CI: 0.7–13.1) were marginally associated with syphilis seroconversion. Conclusion: The high incidence rates of HIV and syphilis in the Shenyang MSM community are significant cause for concern. The seroconversion rate for syphilis, in particular, indicates the high prevalence of high-risk sexual behaviors and the potential for increased HIV transmission. Appropriate interventions that address MSM-specific issues, including stigma, pressures from traditional society, and bisexual behavior, need to be tailored to inform and empower MSM in order to prevent HIV and syphilis in this community.

Background: Natural killer (NK) cells have emerged as pivotal players in innate immunity, especially in the defense against viral infections and tumors. Killer immunoglobulin-like receptors (KIRs) – an important recognition receptor expressed on the surface of NK cells – regulate the inhibition and/or activation of NK cells after interacting with human leukocyte antigen (HLA) class I ligands. Various KIR genes might impact the prognosis of many different diseases. The implications of KIR-HLA interaction in HIV disease progression remains poorly understood.Methods: Here, we studied KIR genotypes, mRNA levels, HLA genotypes, CD4⁺T cell counts and viral loads in our cohort of Human Immunodeficiency Virus (HIV)-infected individuals, a group that includes HIV long-term nonprogressors (LTNPs) and typical progressors (TPs).Results: We found that the frequency of KIR3DS1/L1 heterozygotes with HLA-Bw4-80I gene was much higher in LTNPs than in TPs (P = 0.001) and that the KIR3DL1 homozygotes without HLA-Bw4-80I gene had higher viral loads and lower CD4⁺T cell counts (P = 0.014 andP = 0.021, respectively). Our study also confirmed that homozygosity for the HLA-Bw6 allele was associated with rapid disease progression. In addition to the aforementioned results on the DNA level, we observed that higher level expression of KIR3DS1 mRNA was in LTNP group, and that higher level expression of KIR3DL1 mRNA was in TP group.Conclusions: Our data suggest that different KIR-HLA genotypes and different levels of transcripts associate with HIV disease progression.

Background: Pre-exposure prophylaxis (PrEP) is used as an HIV prevention method by people at substantial risk of HIV infection. This systematic review and meta-analysis evaluates current clinical evidence for use of oral TDF-based PrEP among men who have sex with men. Methods: A comprehensive literature search in PubMed, web of science, Google Scholar and ClinicalTrials.gov was performed. A random-effects meta-analysis was conducted using the event rate (ER) for estimation of the incidence of HIV and grade 3 or 4 adverse events (AE) among PrEP arm and using risk ratio (RR) for comparison of incidence of HIV and grade 3 or 4 AE between PrEP recipients and PrEP non-users. Blood-based adherence levels were also divided into three categories with reference to previous meta-analysis. Subgroup meta-analysis was also performed to evaluate whether blood-based adherence levels moderated the effect of TDF-based PrEP on HIV incidence. Narrative review was used due to inconsistent measurements of risk behavior and drug resistance. This review is registered on the PROSPERO database (CRD42017077965). Results: Fourteen studies were included in the review. Oral TDF-based PrEP significantly reduced HIV incidence with minimum drug resistance and tolerable safety risks (HIV incidence, ER = 1.1%, 95% CI 0.6–2.0%, p < 0.001, RR = 0.244, 95% CI 0.111–0.537, p < 0.001 and grade 3 or 4 AEs, ER = 13.0%, 95% CI 9.9–16.9%, p < 0.001, RR = 1.059, 95% CI 0.824–1.362, p = 0.653). Oral TDF-based PrEP was more effective in reducing HIV incidence with high levels of blood-based PrEP adherence (ER, 0.4%) compared to moderate adherence (2.9%; p < 0.001). Most studies found no association between PrEP use and self-reported sexual behavior. Conclusion: Oral TDF-based PrEP is an effective intervention to prevent against HIV infection among MSM. Well-designed implementation science studies that integrate sociobehavioral and biomedical interventions are needed to identify optimal PrEP delivery models in different populations to translate biomedical efficacy into real-world efficacy.

Recreational drug use (RDU) may result in sexual disinhibition and higher risk for HIV and other sexually transmitted infections (STIs) among men who have sex with men (MSM) in China. We assessed whether RDU was associated with HIV, syphilis, and herpes simplex virus type 2 (HSV-2) within the context of multiple sexual partnerships and unprotected sex. We conducted a cross-sectional study among sexually-active MSM in six Chinese cities (Kunming, Jinan, Changsha, Zhengzhou, Nanjing, and Shanghai) in 2012–2013. We interviewed participants regarding RDU and sexual activity and drew blood for HIV, syphilis, and HSV-2. We fit multiple logistic regression models to assess associations of drug use and HIV, syphilis and HSV-2 infections, controlling for number of sexual partners and unprotected sex. Of 3830 participants, 28% reported ever using ≥1 of these drugs in the past 6 months: popper (alkyl nitrites), ecstasy, ice (methamphetamine), amphetamine, tramadol, and ketamine. In the past six months, 62% of MSM reported ≥2 sexual partners and 76% did not use condoms at last sexual encounter. HIV, syphilis and HSV-2 prevalences were 9.2%, 12.2%, and 10.3%, respectively.RDU was associated with HIV infection (aOR = 1.67; 95% CI, 1.31-2.13). Men with RDU were more likely to report multiple sexual partners (OR = 1.69; 95% CI, 1.44-1.98) and unprotected sex (aOR = 1.25; 95% CI, 1.05-1.49). The RDU-HIV association persisted (aOR = 1.58; 95% CI = 1.23-2.02) after adjusting for numbers of partners. RDU was associated with multiple sexual partnerships, unprotected sex, and HIV among Chinese MSM. It is plausible that RDU is a driver of increased sexual/HIV risk and/or may be an associated behavior with sexually risky lifestyles. Community engagement is needed.