Risk Factors for HSV-2 Infection among Sexual Partners of HSV-2/HIV-1 Co-Infected Persons

<p>Abstract</p> <p>Background</p> <p>Herpes simplex virus type 2 (HSV-2) is the most frequent cause of genital ulcer disease worldwide and has been associated with increased risk for HIV-1 acquisition and transmission. We conducted a cross-sectional analysis of risk factors for HSV-2 infection among HIV-1 uninfected partners, whose partners were co-infected with HIV-1 and HSV-2.</p> <p>Methods</p> <p>Between November 2004 and April 2007, 3408 HIV-discordant couples, in which the HIV-1 infected partners were HSV-2 seropositive with CD4 250 cells/mm³or greater, were enrolled in an HSV-2 suppression trial to prevent HIV-1 transmission at 14 sites in 7 African countries. Clinical & behavioral data, HSV-2 and HIV-1 testing were conducted at enrolment. Univariate and multivariate Poisson regression analyses were performed separately, by gender of the HIV-1 infected partner.</p> <p>Results</p> <p>Among 3354 HIV-1 uninfected participants, 32% were female and overall 71% were HSV-2 seropositive. Among couples with female HIV-1 infected partners, HIV-1 plasma RNA [aPR 1.03; 95% CI: 0.99 to 1.06; p = 0.11] and CD4 count [aPR 1.00; 95% CI: 0.98 to 1.01; p = 0.48] in the HSV-2/HIV-1 dually infected female and circumcision in the HIV-1 uninfected male partner [aPR 0.94; 95% CI: 0.88 to 1.00; p = 0.06] were not associated with reduced risk of HSV-2 seropositivity, after adjusting for other factors.</p> <p>Conclusions</p> <p>In this cross-sectional analysis of African HIV-1 serodiscordant heterosexual couples with prevalent HSV-2 infection in the HIV-1 infected partner, HIV-1 plasma RNA and CD4 count in the dually-infected partner and male circumcision in the HIV-1 uninfected partner were not associated with HSV-2 concordance.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00194519">NCT00194519</a></p

Text message reminders and peer education increase HIV and Syphilis testing among female sex workers: a pilot quasi-experimental study in Uganda.

BACKGROUND: Globally, female sex workers (FSW) are disproportionately affected by HIV and other sexually transmitted infections (STIs). However, uptake of STI and HIV testing services among FSW in sub-Saharan Africa remains low. We aimed to assess the effect of FSW-led peer education and text message reminders on 3-monthly syphilis and HIV testing among FSW in Uganda. METHODS: Between September 2019 and February 2020, we implemented weekly peer education sessions and bi-monthly SMS reminders for FSW in Mbarara (intervention city). Peer education sessions were implemented by 20 FSW, who received five days of basic training as peer educators. We held monthly meetings with peer educators throughout the six-month implementation period. FSW in Mbale (control city) continued to receive standard of care consisting of HIV testing outreach campaigns, and facility-based testing. Using a quasi-experimental design in one intervention city, and one control city, we conducted pre- and post- questionnaire-based surveys on recent syphilis and HIV testing behavior among FSW in July-October 2018, and March 2020. We compared proportions and prevalence ratios at baseline and follow-up using chi-square tests and negative binomial regression. RESULTS: We conducted 436 interviews (200 before/236 after) with FSW. At baseline similar proportions reported taking an HIV test (57 % vs. 54 %; p = 0.72), and a syphilis serology test (35 % vs. 39 %; p = 0.67) in the intervention and control cities, respectively, in the prior three months. After the intervention, this proportion increased to 82 % (95 % confidence interval [CI] 74.0-88.2) for HIV, and 81 % (95 % CI: 73.0-87.0) for syphilis in the intervention city. Relative to baseline in the control city, the proportion testing for HIV was unchanged (52 %) but decreased for syphilis (26 %). CONCLUSIONS: Bi-monthly text message reminders with weekly peer education sessions increased uptake of 3-monthly syphilis and HIV testing in a Ugandan female sex work population and could help increase sex worker engagement in HIV/STI services in line with World Health Organization recommendations

Psychosocial correlates of regular syphilis and HIV screening practices among female sex workers in Uganda: a cross-sectional survey

Abstract: Background: Limited data are available regarding correlates of regular sexually transmitted infections (STIs) and HIV screening among female sex workers (FSW) in Sub-Saharan Africa. In this study, we aimed to assess the frequency of regular syphilis and HIV screening and the psychosocial correlates associated with screening among FSW in Uganda. Methods: This cross-sectional correlational study was conducted among 441 FSW, aged 17–49 years. We enrolled FSW through peer referrals and ascertained self-reported data on number of serological tests for HIV, syphilis and other STIs in the prior 12 months using an interviewer-administered questionnaire. In addition, we assessed attitudes, norms, social influences and self-efficacy towards 3-monthly Syphilis and 6-monthly HIV testing. We estimated the correlates of regular STI and HIV testing using negative binomial regression. Results: Of the respondents 420 (95.2%) reported to have ever taken an HIV test with 297 (67.4%) testing two or more times in the prior 12 months. Over half of the respondents (59%) reported ever taking a syphilis test with only 62 (14.1%) reporting testing three or more times in the prior 12 months. After adjusting for socio-demographics, attitude and norms, high perceived self-efficacy was associated with a 33% increase in the likelihood of repeated HIV testing [prevalence ratio (PR), 1.33, 95% confidence interval (CI) 1.15–1.53] while low perceived confidence was associated with a 25% decrease in the likelihood of repeated HIV testing (PR, 0.75, 95% CI 0.63–0.89). Similarly low attitudes and norms were associated with a decrease of 52.6% (PR, 0.47, 95% CI 0.37–0.61) and 47% (PR, 0.53, 95% CI 0.41–0.69) in the likelihood of repeated syphilis testing respectively. Conclusion: Compared to HIV, uptake of repeated syphilis testing was very low. Correlates of HIV testing include; perceived self-efficacy amidst barriers and perceived confidence for HIV and low attitudes and accepting norms for syphilis. Health campaigns should emphasize overcoming barriers to HIV testing while promoting attitudes and norms including integration of serological syphilis testing and other STIs into HIV services

HIV Protective Efficacy and Correlates of Tenofovir Blood Concentrations in a Clinical Trial of PrEP for HIV Prevention

Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P 40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence

Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2). METHODS: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated. RESULTS: GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups. CONCLUSIONS: Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART

Association between male circumcision and incidence of syphilis in men and women: a prospective study in HIV-1 serodiscordant heterosexual African couples

Background Male circumcision is a primary HIV-1 prevention intervention for men, but whether the procedure reduces the risk of syphilis among men and their female partners is uncertain. We aimed to assess whether male circumcision was associated with incident syphilis in men and in their female partners. Methods In this large prospective cohort study, participants were members of Kenyan and Ugandan HIV-1 serodiscordant heterosexual couples enrolled in a randomised safety and effi cacy clinical trial of pre-exposure prophylaxis for HIV-1 prevention (the Partners PrEP Study). Participants attended monthly or quarterly follow-up visits for up to 36 months. Annually, syphilis serology testing was done and male circumcision status was assessed. We used multivariate Andersen-Gill survival methods, adjusted for age, sexual behaviour, and plasma HIV RNA levels of the HIV-infected partner. Findings 4716 HIV-1 serodiscordant couples (38%) with a man with HIV were followed for a median of 2·75 years. At enrolment, 1575 (53%) men with HIV and 560 (32%) men without HIV were circumcised; an additional 69 (4%) men with HIV and 132 (5%) men without HIV were circumcised during study follow-up. 221 incident syphilis infections were reported: 46 (21%) in men with HIV (incidence 1·10 per 100 person-years), 76 (34%) in men without HIV (1·09), 54 (24%) in women with HIV (0·77), and 45 (24%) in women without HIV (1·11). Male circumcision was associated with a 42% reduction in incident syphilis in men (adjusted hazard ratio [aHR] 0·58, 95% CI 0·37–0·91) including a 62% reduction in men with HIV (0·38, 0·18–0·81), and a non-signifi cant reduction in incident syphilis in men without HIV (0·64, 0·36–1·11). In women, circumcision of their male partners was associated with a 59% reduction in incident syphilis (aHR 0·41, 95% CI 0·25–0·69), including a 75% reduction in women without HIV (0·25, 0·08–0·76) and a 48% reduction in women with HIV (0·52, 0·27–0·97). Interpretation Male circumcision was associated with decreased risk of incident syphilis in men and women. If confi rmed, these results suggest that medical male circumcision could substantially reduce incidence of syphilis and its sequelae

"I felt very small and embarrassed by the health care provider when I requested to be tested for syphilis": barriers and facilitators of regular syphilis and HIV testing among female sex workers in Uganda.

BACKGROUND: Periodic testing of female sex workers (FSW) for sexually transmitted infections (STIs) is a core component of global and national responses to achieve population-level STI elimination. We conducted a qualitative study to explore barriers and facilitators of regular syphilis and HIV testing among FSW in Uganda. METHODS: Within a quasi-experimental study among 436 FSW to assess the effect of peer education and text message reminders on uptake of regular STI and HIV testing among FSW, we conducted 48 qualitative interviews in four cities in Uganda from August-December 2018. We purposively selected FSW who tested for syphilis and HIV every 3-6 months; 12 FSW were interviewed in each city. Sex worker interviews explored: 1) reasons for periodic syphilis and HIV testing; 2) barriers and facilitators of testing; 3) experiences of testing; and 4) challenges faced while seeking testing services. Data were analyzed using thematic content analysis. RESULTS: Thematic analysis revealed individual- and health system-level barriers and facilitators of testing. For syphilis, barriers were a) interpersonal stigma, low perceived severity of syphilis and testing misconceptions (individual); and b) judgmental provider attitudes, paucity of facilities offering syphilis testing, stockouts of test kits and high cost (health system). Facilitators were c) desire to remain healthy, get married and have children, knowing the benefits of early treatment, influence of male partners/clients and normative testing behaviors (individual); and d) sex worker clinics offering dual syphilis/HIV testing (health system). For HIV, barriers included: a) internalized stigma (individual); and b) unfavorable clinic hours, stigma, discrimination, and unfriendly provider (health system). Facilitators were a) motivations to stay healthy and attract clients, habitual testing, self-efficacy, doubts about accuracy of negative test results, and use of post-exposure prophylaxis (individual); and d) availability of testing facilities (health system). Syphilis and HIV had similar testing barriers and facilitators. CONCLUSIONS: HIV programs are likely to be important entry points for syphilis testing among FSW. Multi-level interventions to address testing barriers should consider focusing on these service delivery points. Extending the dual syphilis and HIV testing approach to FSW may improve testing uptake for both infections at public health facilities and decrease population-level incidence

HIV and syphilis testing behaviors among heterosexual male and female sex workers in Uganda

Funder: Janssen Pharmaceuticals (US)Abstract: Background: In Sub-Saharan Africa where HIV disproportionately affects women, heterosexual male sex workers (HMSW) and their female clients are at risk of acquiring or transmitting HIV and other STIs. However, few studies have described HIV and STI risk among HMSW. We aimed to assess and compare recent HIV and syphilis screening practices among HMSW and female sex workers (FSW) in Uganda. Methods: Between August and December 2019, we conducted a cross-sectional study among 100 HMSW and 240 female sex workers (FSW). Participants were enrolled through snowball sampling, and an interviewer-administered questionnaire used to collect data on HIV and syphilis testing in the prior 12 and 6 months respectively. Integrated change model constructs were used to assess intentions, attitudes, social influences, norms and self-efficacy of 3-monthly Syphilis and 6-monthly HIV testing. Predictors of HIV and syphilis recent testing behaviors were estimated using negative binomial regression. Results: We enrolled 340 sex workers of whom 100 (29%) were HMSW. The median age was 27 years [interquartile range (IQR) 25–30] for HMSW and 26 years [IQR], (23–29) for FSW. The median duration of sex work was 36 and 30 months for HMSW and FSW, respectively. HMSW were significantly less likely than FSW to have tested for HIV in the prior 12 months (50% vs. 86%; p = 0.001). For MSW, non-testing for HIV was associated with higher education [adjusted prevalence ratio (aPR) 1.66; 95% confidence interval (CI) 1.09–2.50], poor intention to seek HIV testing (aPR 1.64; 95% CI 1.35–2.04), perception that 6-monthly HIV testing was not normative (aPR 1.33; 95% CI 1.09–1.67) and low self-efficacy (aPR 1.41; 95% CI 1.12–1.79). Not testing for syphilis was associated with low intention to seek testing (aPR 3.13; 95% CI 2.13–4.55), low self-efficacy (aPR 2.56; 95% CI 1.35–4.76), negative testing attitudes (aPR 2.33; 95% CI 1.64–3.33), and perception that regular testing was not normative (aPR 1.59; 95% CI 1.14–2.22). Conclusions: Non-testing for HIV and syphilis was common among HMSW relative to FSW. Future studies should evaluate strategies to increase testing uptake for this neglected sub-population of sex workers

Characteristics of HIV-1 Serodiscordant Couples Enrolled in a Clinical Trial of Antiretroviral Pre-Exposure Prophylaxis for HIV-1 Prevention

Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.HIV-1 serodiscordant couples, in which the HIV-1 infected partner did not meet national guidelines for initiation of antiretroviral therapy, were enrolled at 9 research sites in Kenya and Uganda. The HIV-1 susceptible partner was randomized to daily oral tenofovir, emtricitabine-tenofovir, or matching placebo with monthly follow-up for 24-36 months.From July 2008 to November 2010, 7920 HIV-1 serodiscordant couples were screened and 4758 enrolled. For 62% (2966/4758) of enrolled couples, the HIV-1 susceptible partner was male. Median age was 33 years for HIV-1 susceptible and HIV-1 infected partners [IQR (28-40) and (26-39) respectively]. Most couples (98%) were married, with a median duration of partnership of 7.0 years (IQR 3.0-14.0) and recent knowledge of their serodiscordant status [median 0.4 years (IQR 0.1-2.0)]. During the month prior to enrollment, couples reported a median of 4 sex acts (IQR 2-8); 27% reported unprotected sex and 14% of male and 1% of female HIV-1 susceptible partners reported sex with outside partners. Among HIV-1 infected partners, the median plasma HIV-1 level was 3.94 log(10) copies/mL (IQR 3.31-4.53) and median CD4 count was 496 cells/µL (IQR 375-662); the majority (64%) had WHO stage 1 HIV-1 disease.Couples at high risk of HIV-1 transmission were rapidly recruited into the Partners PrEP Study, the largest efficacy trial of oral PrEP. (ClinicalTrials.gov NCT00557245)