Rebecca G. Nowak

Male circumcision for the prevention of HSV-2 and HPV infections and syphilis.

BACKGROUND Male circumcision significantly reduced the incidence of human immunodeficiency virus (HIV) infection among men in three clinical trials. We assessed the efficacy of male circumcision for the prevention of herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) infections and syphilis in HIV-negative adolescent boys and men. METHODS We enrolled 5534 HIV-negative, uncircumcised male subjects between the ages of 15 and 49 years in two trials of male circumcision for the prevention of HIV and other sexually transmitted infections. Of these subjects, 3393 (61.3%) were HSV-2-seronegative at enrollment. Of the seronegative subjects, 1684 had been randomly assigned to undergo immediate circumcision (intervention group) and 1709 to undergo circumcision after 24 months (control group). At baseline and at 6, 12, and 24 months, we tested subjects for HSV-2 and HIV infection and syphilis, along with performing physical examinations and conducting interviews. In addition, we evaluated a subgroup of subjects for HPV infection at baseline and at 24 months. RESULTS At 24 months, the cumulative probability of HSV-2 seroconversion was 7.8% in the intervention group and 10.3% in the control group (adjusted hazard ratio in the intervention group, 0.72; 95% confidence interval [CI], 0.56 to 0.92; P=0.008). The prevalence of high-risk HPV genotypes was 18.0% in the intervention group and 27.9% in the control group (adjusted risk ratio, 0.65; 95% CI, 0.46 to 0.90; P=0.009). However, no significant difference between the two study groups was observed in the incidence of syphilis (adjusted hazard ratio, 1.10; 95% CI, 0.75 to 1.65; P=0.44). CONCLUSIONS In addition to decreasing the incidence of HIV infection, male circumcision significantly reduced the incidence of HSV-2 infection and the prevalence of HPV infection, findings that underscore the potential public health benefits of the procedure. (ClinicalTrials.gov numbers, NCT00425984 and NCT00124878.)

The association between cervical human papillomavirus infection and HIV acquisition among women in Zimbabwe

Background:The prevalence of human papillomavirus (HPV) is higher among HIV-positive women, but the prevalence of HPV prior to HIV acquisition has not been carefully evaluated. Objective:This study evaluated whether HPV infection is independently associated with heterosexual HIV acquisition in a cohort of Zimbabwean women. Design:Case–control study nested within a large multicenter cohort study (HC-HIV). Methods:Cases consisted of Zimbabwean women with incident HIV infection observed during follow-up (n = 145). HIV-uninfected controls were selected and matched to cases (n = 446). The prevalence of cervical HPV infections was compared at the visit prior to HIV infection in the cases and at the same follow-up visit in the matched controls. Results:The odds of acquiring HIV were 2.4 times higher in women with prior cervical HPV infection after adjustment for behavioral and biologic risk factors. There was no statistically significant difference in the risk of HIV acquisition between women infected with high-risk vs. low-risk HPV types. Loss of detection of at least one HPV DNA type was significantly associated with HIV acquisition [odd ratio = 5.4 (95% confidence interval 2.9–9.9)] (P < .0001). Conclusion:Cervical HPV infection is associated with HIV acquisition among women residing in a region with a high prevalence of both infections. Further studies are required to evaluate whether the observed association is causal.

Increases in Human Papillomavirus Detection During Early HIV Infection Among Women in Zimbabwe

BACKGROUND Individuals who acquire human immunodeficiency virus (HIV) may experience an immediate disruption of genital tract immunity, altering the ability to mount a local and effective immune response. This study examined the impact of early HIV infection on new detection of human papillomavirus (HPV). METHODS One hundred fifty-five Zimbabwean women with observation periods before and after HIV acquisition and 486 HIV-uninfected women were selected from a cohort study evaluating hormonal contraceptive use and risk of HIV acquisition. Study visits occurred at 3-month intervals. Cervical swab samples available from up to 6 months before, at, and up to 6 months after the visit when HIV was first detected were typed for 37 HPV genotypes or subtypes. RESULTS We observed ∼5-fold higher odds of multiple (≥2) new HPV detections only after HIV acquisition, relative to HIV-negative women after adjusting for sexual behavior and concurrent genital tract infections. We also observed ∼2.5-fold higher odds of single new HPV detections at visits before and after HIV acquisition, relative to HIV-uninfected women in multivariable models. CONCLUSIONS These findings suggest that HIV infection has an immediate impact on genital tract immunity, as evidenced by the high risk of multiple new HPV detections immediately after HIV acquisition.

Uptake of treatment as prevention for HIV and continuum of care among HIV-positive men who have sex with men in Nigeria.

Background:Experimental evidence has shown that treatment of HIV infection with antiretroviral therapy (ART) prevents heterosexual transmission of HIV to an uninfected partner. However, the “real-world” application of this strategy to key populations such as men who have sex with men (MSM) has been limited. We report findings on acceptability of a treatment as prevention (TasP) strategy among HIV-infected MSM at a Trusted Community Center providing comprehensive HIV prevention and treatment services to MSM in Abuja, Nigeria. Methods:Using respondent-driven sampling (RDS), MSM who were 16 years and older and have engaged in either receptive or insertive anal intercourse within the previous 12 months were recruited into a prospective combination HIV prevention and treatment study (TRUST). Two weeks after enrollment, HIV testing and counseling was conducted. At each 3-month follow-up visits, HIV-infected individuals underwent clinical and laboratory evaluation, including CD4 count, plasma HIV viral load, immediate 3 weekly sessions of ART preparation, and then ART initiation per TasP strategy irrespective of CD4 count. Reasons for not engaging in pre-TasP preparation and TasP were documented. Characteristics associated with TasP engagement and loss to follow-up (LTFU) were determined using logistic and Cox regression, respectively. Results:Of 186 HIV-positive MSM enrolled, 58 (31.2%) were on ART at the time of recruitment, whereas 128 (68.8%) were ART-naive and provided opportunity for engaging TasP. Of these, 70 (54.7%) engaged in TasP. Compared with MSM who did not engage in TasP, those who engaged had significantly lower mean CD4 count (P = 0.001), were more likely to be Christian (P = 0.01), and had disclosed being MSM to family (P = 0.02) or health care providers (P = 0.02). In multivariate models, disclosure of being MSM to health care providers remained significantly associated with uptake of TasP. Among individuals engaged in TasP, 10% were LTFU in care at 18 months since enrollment. Being engaged in TasP (relative hazards = 0.08, P < 0.001) and on ART (relative hazards = 0.17, P < 0.001) were associated with decreased risk of LTFU. Conclusions:Although there was high acceptance of HIV testing and low LTFU among individuals who were already on ART or engaged in TasP, a higher than expected proportion did not engage in TasP, suggesting the need for customized treatment preparation and an increase in enabling environments to support HIV treatment access with this key population.

Rectal microbiota among HIV-uninfected, untreated HIV, and treated HIV-infected men who have sex with men (MSM) in Nigeria.

Objective: Untreated advanced HIV infection alters the gut microbiota, but it is unclear whether antiretroviral therapy (ART) reverses these changes. We compared the composition of the rectal microbiota among three groups of men who have sex with men (MSM): HIV-uninfected, untreated HIV, and ART-treated HIV-infected. Design: A cross-sectional study was conducted among 130 MSM (55 HIV-uninfected, 41 untreated HIV, and 34 ART-treated HIV) in Abuja, Nigeria. Methods: Bacterial 16S rRNA genes were amplified from rectal swabs, sequenced and clustered into Genera-level operational taxonomic units. Alpha diversity was quantified using the Shannon index and compared among groups using the Kruskal–Wallis test; associations with other scale variables were quantified using Spearmans rank correlation (Rs). The relative abundance of the top 15 taxa was compared according to HIV infection/treatment status using the Wilcoxon rank sum test. Results: HIV-treated MSM had a decrease in a commensal phylum, Bacteroidetes (P < 0.01). Alpha diversity was positively correlated with viral loads (Rs = 0.32, P < 0.01). Statistically significant shifts in relative abundance of rectal microbiota for the HIV-treated group included a decrease in the most abundant bacteria, Prevotella (P = 0.02) and an increase in pathogenic bacteria, Peptoniphilus (P = 0.04), Finegoldia (P = 0.01), Anaerococcus (P = 0.03), and Campylobacter (P = 0.03) compared with the other groups. Conclusion: Untreated HIV infection does not significantly alter the rectal microbiota, whereas prior treatment is associated with a shift toward a more pathogenic pattern of microbiota. Treatment with an antibiotic, co-trimoxazole, in conjunction with ART may have contributed to this shift.

Asymptomatic Lymphogranuloma Venereum among Nigerian Men who have Sex with Men

Abstract Background Among men who have sex with men (MSM), lymphogranuloma venereum (LGV) has been associated with proctocolitis that can lead to chronic complications and requires a longer course of antibiotic therapy than is recommended for infections due to other serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical features of LGV among Nigerian MSM diagnosed with anorectal CT. Methods MSM were recruited into the ongoing RV368 cohort in Lagos, Nigeria, using respondent-driven sampling. Participants were screened for HIV and bacterial sexually transmitted infections (STIs) every three months for up to 18 months. HIV was diagnosed using a parallel algorithm of rapid tests on fingerstick blood samples. PCR testing for Neisseria gonorrheae and CTwas performed on voided urine, oropharyngeal swab, and rectal swab specimens. For this analysis, prevalent and incident cases of rectal CT infection underwent additional testing to identify LGV serovars utilizing novel real-time PCR assays specific for the L serovars of CT Chlamydia trachomatis. Results From 28 April 2014–19 July 2016, 420 men underwent screening for rectal STIs, including 66 (15.7%) who had prevalent rectal infection with CT. An additional 68 participants developed incident infections during 208 person-years of follow-up. Of 134 eligible rectal swab specimens, 128 underwent further testing for LGV serovars. Seven (5.5%) of the tested samples were identified as LGV serovars of CT. None of the seven participants with LGV reported any symptoms such as fever or rectal pain. Two of the participants with LGV were simultaneously co-infected with rectal gonorrhea. HIV co-infection was common among participants with both LGV and non-LGV serovars of CT (71% and 77%, respectively, P = 0.74). Conclusion LGV was uncommon but present among Nigerian MSM in this study. LGV needs to be considered even in asymptomatic cases, particularly if anorectal CT infection fails to respond to the usual course of therapy. Consistent screening for L serovars of CT, or empiric treatment for LGV in cases with a high suspicion for this diagnosis, could potentially improve patient outcomes and decrease transmission. Disclosures All authors: No reported disclosures.

P-B18 Prevalence of anal high-risk human papillomavirus infections among HIV-positive and HIV-negative men who have sex with men (MSM) in Nigeria

Introduction:Prevalence estimates of anal high-risk human papillomavirus (HR-HPV) are needed in sub-Saharan Africa where HIV is endemic. This study evaluated anal HR-HPV in Nigeria among HIV-positive and HIV-negative men who have sex with men (MSM) for future immunization recommendations. Methods:We conducted a cross-sectional study to compare the prevalence of anal HR-HPV infections between 64 HIV- negative and 90 HIV-positive MSM. Multivariate Poisson regression analyses were used to examine demographic and behavioral risk factors associated with any HR-HPV infections. Results:The median age of the 154 participants was 25 years [interquartile range (IQR): 22–28, range: 16–38] and the median age at initiation of anal sex with another man was 16 years (IQR: 13–18, range: 7–29). The prevalence of anal HR-HPV was higher among HIV-positive than HIV-negative MSM (91.1% vs. 40.6%, P < 0.001). In the multivariate analysis, HIV infection [adjusted prevalence ratio (aPR): 2.02, 95% CI: 1.49 to 2.72], 10 years or more since anal sexual debut (aPR: 1.26, 95% CI: 1.07 to 1.49), and concurrent relationships with men (aPR: 1.31, 95% CI: 1.04 to 1.67) were associated with increased anal HR-HPV prevalence. Conclusions:Anal HR-HPV infection is high for young Nigerian MSM and rates are amplified in those co-infected with HIV. Providing universal coverage as well as catch-up immunization for young men may be a more effective prevention strategy in Nigeria.