Suzanna C. Francis

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.

The vaginal microbiota: what have we learned after a decade of molecular characterization?

We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A) to determine if consistent molecular vaginal microbiota (VMB) composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization) was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV) is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV), and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB.

Intravaginal practices, vaginal infections and HIV acquisition: systematic review and meta-analysis

Background Intravaginal practices are commonly used by women to manage their vaginal health and sexual life. These practices could, however, affect intravaginal mucosal integrity. The objectives of this study were to examine evidence for associations between: intravaginal practices and acquisition of HIV infection; intravaginal practices and vaginal infections; and vaginal infections and HIV acquisition. Methodology/Principal Findings We conducted a systematic review of prospective longitudinal studies, searching 15 electronic databases of journals and abstracts from two international conferences to 31st January 2008. Relevant articles were selected and data extracted in duplicate. Results were examined visually in forest plots and combined using random effects meta-analysis where appropriate. Of 2120 unique references we included 22 publications from 15 different studies in sub-Saharan Africa and the USA. Seven publications from five studies examined a range of intravaginal practices and HIV infection. No specific vaginal practices showed a protective effect against HIV or vaginal infections. Insertion of products for sex was associated with HIV in unadjusted analyses; only one study gave an adjusted estimate, which showed no association (hazard ratio 1.09, 95% confidence interval, CI 0.71, 1.67). HIV incidence was higher in women reporting intravaginal cleansing but confidence intervals were wide and heterogeneity high (adjusted hazard ratio 1.88, 95%CI 0.53, 6.69, I2 83.2%). HIV incidence was higher in women with bacterial vaginosis (adjusted effect 1.57, 95%CI 1.26, 1.94, I2 19.0%) and Trichomonas vaginalis (adjusted effect 1.64, 95%CI 1.28, 2.09, I2 0.0%). Conclusions/Significance A pathway linking intravaginal cleaning practices with vaginal infections that increase susceptibility to HIV infection is plausible but conclusive evidence is lacking. Intravaginal practices do not appear to protect women from vaginal infections or HIV and some might be harmful.

HIV and Other Sexually Transmitted Infections in a Cohort of Women Involved in High-Risk Sexual Behavior in Kampala, Uganda

Background: Uganda has long been successful in controlling the HIV epidemic; however, there is evidence that HIV prevalence and incidence are increasing again. Data on the HIV/STI epidemic among sex workers are so far lacking from Uganda. This paper describes the baseline epidemiology of HIV/STI in a newly established cohort of women involved in high-risk sexual behavior in Kampala, Uganda. Methods Women were recruited from red-light areas in Kampala. Between April 2008 and May 2009, 1027 eligible women were enrolled. Sociodemographic and behavioral information were collected; blood and genital samples were tested for HIV/STI. Risk factors for HIV infection were examined using multivariate logistic regression. Results: HIV seroprevalence was 37%. The prevalence of Neisseria gonorrhoeae was 13%, Chlamydia trachomatis, 9%; Trichomonas vaginalis, 17%; bacterial vaginosis, 56% and candida infection, 11%. Eighty percent had herpes simplex virus 2 antibodies (HSV-2), 21% were TPHA-positive and 10% had active syphilis (RPR+TPHA+). In 3% of the genital ulcers, Treponema pallidum (TP) was identified, Haemophilus ducreyi in 6%, and HSV-2 in 35%. Prevalent HIV was independently associated with older age, being widowed, lack of education, sex work as sole income, street-based sex work, not knowing HIV-status, using alcohol, and intravaginal cleansing with soap. HIV infection was associated with N. gonorrhoeae, T. vaginalis, bacterial vaginosis, HSV-2 seropositivity and active syphilis. Conclusions: Prevalence of HIV/STI is high among women involved in high-risk sexual behavior in Kampala. Targeted HIV prevention interventions including regular STI screening, voluntary HIV testing and counseling, condom promotion, and counseling for reducing alcohol use are urgently needed in this population.

Sexually transmitted infections: challenges ahead

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

Prevalence of rectal Trichomonas vaginalis and Mycoplasma genitalium in male patients at the San Francisco STD clinic, 2005-2006.

Sexually transmitted infections (STI), such as Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes Simplex Virus (HSV), and Treponema pallidum, are common causes of proctitis among gay men and other men who have sex with men (MSM) [1, 2]. Inflammatory proctitis caused by an STI may increase the susceptibility and infectivity of HIV[3, 4]. In many cases of proctitis, however, no etiological organism is detected[1]. The advent of nucleic acid amplification techniques (NAATs) presents an opportunity to detect organisms previously difficult to isolate from the rectum. Two such organisms, Trichomonas vaginalis and Mycoplasma genitalium, have been implicated in male urethritis, female cervicitis and endometrial infection[5-11].

Epidemiology of Curable Sexually Transmitted Infections among Women at Increased Risk for HIV in Northwestern Tanzania: Inadequacy of Syndromic Management

Background Curable, non-viral pathogens account for a significant burden of sexually transmitted infections (STIs), and there is established evidence that STIs increase both HIV acquisition and transmission. We investigated the prevalence, trends, and factors associated with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Treponema pallidum, and the performance of syndromic management, among a cohort of women working in bars, hotels, and other food and recreational facilities near large-scale mines in northwestern Tanzania. Methods HIV-negative women aged 18–44 years (N = 966) were enrolled and followed for 12 months in a microbicides feasibility study. We collected sociodemographic and behavioural data, performed clinical examinations, and tested for STIs, at enrolment and 3-monthly. Risk factors for STIs were investigated using logistic regression models with random effects. Sensitivity, specificity and predictive values of syndromic management were calculated. Results At enrolment, the prevalences of C. trachomatis, N. gonorrhoeae, T. vaginalis, and high-titre active syphilis were 111/956 (12%), 42/955 (4%), 184/945 (19%) and 46/965 (5%), respectively. There were significant decreases over time for C. trachomatis and T. vaginalis (OR trend per month: 0.94 [95% CI 0.91, 0.97]; and 0.95 [0.93, 0.98], respectively; both p<0.001). The majority of these infections were not diagnosed by the corresponding syndrome; therefore, most participants were not treated at the diagnosis visit. Syndromic management was poorly predictive of laboratory-diagnosed infections. We identified a number of risk factors for STIs, including low educational level, some sexual behaviours, and ever having been pregnant. Conclusions This analysis demonstrates that the prevalences of curable STIs are high among women who work in food and recreational facilities in northwestern Tanzania. Most of these infections are missed by syndromic management. Accurate and affordable rapid-point-of-care tests and innovative interventions are needed to reduce the burden of STIs in this population which is at increased risk for HIV.

The Epidemiology of HIV and HSV-2 Infections among Women Participating in Microbicide and Vaccine Feasibility Studies in Northern Tanzania

Objectives To prepare for future HIV prevention trials, we conducted prospective cohort studies among women working in food and recreational facilities in northern Tanzania. We examined the prevalence and incidence of HIV and HSV-2, and associated risk factors. Methods Women aged 18–44 years working in food and recreational facilities were screened to determine their eligibility for the studies. Between 2008–2010, HIV-negative women were enrolled and followed for 12 months. At enrolment and 3-monthly, we collected socio-demographic and behavioural data, and performed clinical examinations for collection of biological specimens that were tested for reproductive tract infections. Risk factors for HIV and HSV-2 incidence were investigated using Poisson regression models. Results We screened 2,229 and enrolled 1,378 women. The median age was 27 years (interquartile range, IQR 22, 33), and median duration working at current facility was 2 years. The prevalences of HIV at screening and HSV-2 at enrolment were 16% and 67%, respectively. Attendance at the 12-month visit was 86%. HIV and HSV-2 incidence rates were 3.7 (95% confidence interval, CI: 2.8,5.1) and 28.6 (95% CI: 23.5,35.0)/100 person-years, respectively. Women who were separated, divorced, or widowed were at increased risk of HIV (adjusted incidence rate ratio, aRR = 6.63; 95% CI: 1.97,22.2) and HSV-2 (aRR = 2.00; 95% CI: 1.15,3.47) compared with married women. Women reporting ≥3 partners in the past 3 months were at higher HIV risk compared with women with 0–1 partner (aRR = 4.75; 95% CI: 2.10,10.8), while those who had reached secondary education or above were at lower risk of HSV-2 compared with women with incomplete primary education (aRR = 0.42; 95% CI: 0.22,0.82). Conclusions HIV and HSV-2 rates remain substantially higher in this cohort than in the general population, indicating urgent need for effective interventions. These studies demonstrate the feasibility of conducting trials to test new interventions in this highly-mobile population.

Understanding motives for intravaginal practices amongst Tanzanian and Ugandan women at high risk of HIV infection: The embodiment of social and cultural norms and well-being

Some types of intravaginal practices (IVP) may increase the risk for HIV acquisition. This is particularly worrisome for populations with dual high prevalence of HIV and IVP. Women involved in transactional sex are at increased risk for HIV infection in sub-Saharan Africa. Social, cultural and economic influences are strong drivers of IVP in this population. To explore this, we carried out a qualitative research study to investigate the drivers and motivations for using IVP within a large observational study of women at high risk of HIV in Tanzania and Uganda from September 2008 to September 2009. Of the 201 women selected, 176 women took part in a semi-structured in-depth interview. Additionally, in Tanzania, eight focus group discussions among study participants and community members were carried out to obtain information on community norms and expectations. IVP were motivated by overlapping concerns with hygiene, morality, sexual pleasure, fertility, relationship security, and economic security. These motives were driven by the need to meet cultural and social expectations of womanhood, and at the same time attend to personal well-being. Among women involved in transactional sex in East Africa, interventions aimed at modifying or eliminating IVP should attend to local cultural and social norms as well as the individual as an agent of change.