Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls: study protocol of a cluster-randomised controlled trial in western Kenya.

BACKGROUND: Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls' health, school equity, and life-chances. METHODS: Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls' assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout. DISCUSSION: If proved safe and effective, the interventions offer a potential contribution toward girls' schooling, health, and equity in low- and middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT03051789 , 15th February 2017.

Cash transfers and HIV/HSV-2 prevalence: A replication of a cluster randomized trial in Malawi.

INTRODUCTION: In this paper we perform a replication analysis of "Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial" by Sarah Baird and others published in "The Lancet" in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13-22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. METHODS: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. RESULTS: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. CONCLUSIONS: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution.

Herpes simplex virus 1 and 2 educational assessment of young adults in rural southwest Virginia.

PURPOSE: Herpes simplex virus 2 (HSV-2) causes genital herpes, one of the most common sexually transmitted infections (STIs) in the U.S. HSV-1, commonly associated with cold sores, is increasing as a cause of genital herpes. Abstinence-only sexual health classes, commonly taught in Virginia, generate young adults who are under-educated in sexual health, increasing STI risks. College students in southwest Virginia were surveyed to assess comprehensiveness of high school health education regarding HSV-1 and HSV-2 and to identify students' preferred methods for STI education. METHODS: To obtain data on knowledge of HSV, comprehensiveness of sexual health education in high school, and preferred learning methods, 237 college students participated in an online questionnaire and 28 students were interviewed using structured interviews. RESULTS: Questionnaire and interview data indicated that Family Life Education classes need to include more comprehensive information on prevention, viral transmission, and differences between HSV-1 and HSV-2. The majority of total respondents (both the questionnaire and interview) (65%) reported non-comprehensive high school sexual health education. The majority of interview (79%) and questionnaire (55%) respondents wished they had learned more about herpes and other STIs in high school. Education preferences of both interviewed and surveyed respondents included interactive internet programs or games, more realistic lectures, and learning about STIs later in high school when students reported greater sexual activity. CONCLUSION: Our results indicate that more comprehensive sexual health education is needed and wanted by students in southwest Virginia. More relevant educational programs should be implemented for VA high school students utilizing technology and interactive methods to improve student engagement in sexual health education. IMPLICATIONS AND CONTRIBUTION: These studies provide information on knowledge of herpes simplex viruses among college students, comprehensiveness of sexual health education received in high schools, and preferred methods to learn about HSV and other STIs. These studies inform the facilitation of improved health education practices and programs for high school and college students.

Multipurpose prevention technologies for sexual and reproductive health: mapping global needs for introduction of new preventive products.

OBJECTIVES: Worldwide, women face sexual and reproductive health (SRH) risks including unintended pregnancy and sexually transmitted infections (STIs) including HIV. Multipurpose prevention technologies (MPTs) combine protection against two or more SRH risks into one product. Male and female condoms are the only currently available MPT products, but several other forms of MPTs are in development. We examined the global distribution of selected SRH issues to determine where various risks have the greatest geographical overlap. STUDY DESIGN: We examined four indicators relevant to MPTs in development: HIV prevalence, herpes simplex virus type 2 prevalence (HSV-2), human papillomavirus prevalence (HPV) and the proportion of women with unmet need for modern contraception. Using ArcGIS Desktop, we mapped these indicators individually and in combination on choropleth and graduated symbol maps. We conducted a principal components analysis to reduce data and enable visual mapping of all four indicators on one graphic to identify overlap. RESULTS: Our findings document the greatest overlapping risks in Sub-Saharan Africa, and we specify countries in greatest need by specific MPT indication. CONCLUSIONS: These results can inform strategic planning for MPT introduction, market segmentation and demand generation; data limitations also highlight the need for improved (non-HIV) STI surveillance globally. IMPLICATIONS: MPTs are products in development with the potential to empower women to prevent two or more SRH risks. Geographic analysis of overlapping SRH risks demonstrates particularly high need in Sub-Saharan Africa. This study can help to inform strategic planning for MPT introduction, market segmentation and demand generation.

Education, HIV, and Early Fertility: Experimental Evidence from Kenya.

A seven-year randomized evaluation suggests education subsidies reduce adolescent girls' dropout, pregnancy, and marriage but not sexually transmitted infection (STI). The government's HIV curriculum, which stresses abstinence until marriage, does not reduce pregnancy or STI. Both programs combined reduce STI more, but cut dropout and pregnancy less, than education subsidies alone. These results are inconsistent with a model of schooling and sexual behavior in which both pregnancy and STI are determined by one factor (unprotected sex), but consistent with a two-factor model in which choices between committed and casual relationships also affect these outcomes.

Non-culpable ignorance and HIV criminalisation.

In this essay, I argue that any legal framework that addresses sexual transmission of HIV should be sensitive to the way that culpability can be mitigated by moral and factual ignorance. Though it is wrong to transmit HIV, public officials should be wary of criminalising transmission because people with HIV may be excused if they suffer from blameless moral or factual ignorance. I begin with the widely shared premise that blameless ignorance about one's HIV status is an excuse for sexual transmission of infections. I then extend this premise to other kinds of non-moral ignorance about HIV. Next, I argue that blameless moral ignorance also excuses transmission of HIV. There is some evidence of significant blameless non-moral and moral ignorance about HIV transmission. In these cases, transmission is excused. In light of the presence of moral and non-moral ignorance about HIV, I conclude that public health officials should encourage moral deliberation about HIV transmission and also that criminal penalties for HIV transmission are unwarranted even in some cases of knowing or intentional transmission.

Use of agent-based simulations to design and interpret HIV clinical trials.

In this study, we illustrate the utility of an agent-based simulation to inform a trial design and how this supports outcome interpretation of randomized controlled trials (RCTs). We developed agent-based Monte Carlo models to simulate existing landmark HIV RCTs, such as the Partners in Prevention HSV/HIV Transmission Study. We simulated a variation of this study using valacyclovir therapy as the intervention, and we used a male circumcision RCT based on the Rakai Male Circumcision Trial. Our results indicate that a small fraction (20%) of the simulated Partners in Prevention HSV/HIV Transmission Study realizations rejected the null hypothesis, which was no effect from the intervention. Our results also suggest that an RCT designed to evaluate the effectiveness of a more potent drug regimen for HSV-2 suppression (valacyclovir therapy) is more likely to identify the efficacy of the intervention. For the male circumcision RCT simulation, the greater biological effect of the male circumcision yielded a major fraction (81%) of RCT realizations' that rejects the null hypothesis, which was no effect from the intervention. Our study highlights how agent-based simulations synthesize individual variation in the epidemiological context of the RCT. This methodology will be particularly useful for designing RCTs aimed at evaluating combination prevention interventions in community-based RCTs, wherein an intervention׳s effectiveness is challenging to predict.

Cost-effectiveness of tenofovir gel in urban South Africa: model projections of HIV impact and threshold product prices.

BACKGROUND: There is urgent need for effective HIV prevention methods that women can initiate. The CAPRISA 004 trial showed that a tenofovir-based vaginal microbicide had significant impact on HIV incidence among women. This study uses the trial findings to estimate the population-level impact of the gel on HIV and HSV-2 transmission, and price thresholds at which widespread product introduction would be as cost-effective as male circumcision in urban South Africa. METHODS: The estimated 'per sex-act' HIV and HSV-2 efficacies were imputed from CAPRISA 004. A dynamic HIV/STI transmission model, parameterised and fitted to Gauteng (HIV prevalence of 16.9% in 2008), South Africa, was used to estimate the impact of gel use over 15 years. Uptake was assumed to increase linearly to 30% over 10 years, with gel use in 72% of sex-acts. Full economic programme and averted HIV treatment costs were modelled. Cost per DALY averted is estimated and a microbicide price that equalises its cost-effectiveness to that of male circumcision is estimated. RESULTS: Using plausible assumptions about product introduction, we predict that tenofovir gel use could lead to a 12.5% and 4.9% reduction in HIV and HSV-2 incidence respectively, by year 15. Microbicide introduction is predicted to be highly cost-effective (under $300 per DALY averted), though the dose price would need to be just $0.12 to be equally cost-effective as male circumcision. A single dose or highly effective (83% HIV efficacy per sex-act) regimen would allow for more realistic threshold prices ($0.25 and $0.33 per dose, respectively). CONCLUSIONS: These findings show that an effective coitally-dependent microbicide could reduce HIV incidence by 12.5% in this setting, if current condom use is maintained. For microbicides to be in the range of the most cost-effective HIV prevention interventions, product costs will need to decrease substantially.

Financial implications of male circumcision scale-up for the prevention of HIV and other sexually transmitted infections in a sub-Saharan African community.

BACKGROUND: The financial implications of male circumcision (MC) scale-up in sub-Saharan Africa associated with reduced HIV have been evaluated. However, no analysis has incorporated the expected reduction of a comprehensive set of other sexually transmitted infections including human papillomavirus, herpes simplex virus type 2, genital ulcer disease, bacterial vaginosis, and trichomoniasis. METHODS: A Markov model tracked a dynamic population undergoing potential MC scale-up, as individuals experienced MC procedures, procedure-related adverse events, and MC-reduced sexually transmitted infections and accrued any associated costs. Rakai, Uganda, was used as a prototypical rural sub-Saharan African community. Monte Carlo microsimulations evaluated outcomes under 4 alternative scale-up strategies to reach 80% MC coverage among men aged 15 to 49 years, in addition to a baseline strategy defined by current MC rates in central Uganda. Financial outcomes included direct medical expenses only and were evaluated over 5 and 25 years. Costs were discounted to the beginning of each period, coinciding with the start of MC scale-up, and expressed in US $2012. RESULTS: Cost savings from infections averted by MC vary from US $197,531 after 5 years of a scale-up program focusing on adolescent/adult procedures to more than US $13 million after 25 years, under a strategy incorporating increased infant MCs. Over a 5-year period, reduction in HIV contributes to 50% of cost savings, and for 25 years, this contribution rises to nearly 90%. CONCLUSIONS: Sexually transmitted infections other than HIV contribute to cost savings associated with MC scale-up. Previous analyses, focusing exclusively on the financial impact through averted HIV, may have underestimated true cost savings by 10% to 50%.

Results of a pilot test of a brief computer-assisted tailored HIV prevention intervention for use with a range of demographic and risk groups.

There is a need for brief HIV prevention interventions that can be disseminated and implemented widely. This article reports the results of a small randomized field experiment that compared the relative effects of a brief two-session counselor-delivered computer-tailored intervention and a control condition. The intervention is designed for use with African-American, non-Hispanic white and Hispanic males and females who may be at risk of HIV through unprotected sex, selling sex, male to male sex, injecting drug use or use of stimulants. Participants (n = 120) were recruited using a quota sampling approach and randomized using block randomization, which resulted in ten male and ten female participants of each racial/ethnic group (i.e. African-American, non-Hispanic white and Hispanic) being assigned to either the intervention or a control arm. In logistic regression analyses using a generalized estimating equations approach, at 3-month followup, participants in the intervention arm were more likely than participants in the control arm to report condom use at last sex (Odds ratio [OR] = 4.75; 95 % Confidence interval [CI] = 1.70-13.26; p = 0.003). The findings suggest that a brief tailored intervention may increase condom use. Larger studies with longer followups are needed to determine if these results can be replicated.

Spectrum bias and loss of statistical power in discordant couple studies of sexually transmitted infections.

BACKGROUND: Discordant couple studies are frequently used to evaluate preventive interventions for sexually transmitted infections (STI). This study design may be vulnerable to spectrum bias when transmission risk is heterogeneous. METHODS: We used Markov models to assess the effect of heterogeneous transmission risk on the ability to detect effective interventions using a discordant couple study design. We also evaluated the implications that such bias may have for statistical power. Models incorporated potential health states in a population of initially infection-discordant couples, according to infection status with a hypothetical STI and participation in a hypothetical clinical research study. We evaluated the effect of length of discordant relationship at time of study enrollment, the shape of distribution describing transmission risk among couples, and the effect of sex-specific differential transmission probabilities, on model outcomes. RESULTS: The results demonstrate that discordant couple studies are prone to spectrum bias, the degree of which is affected by the shape of the underlying transmission probability density function. CONCLUSIONS: Such bias could lead to unexpected study findings, including gender-specific vaccine effects, and loss of statistical power, making this an important and underrecognized consideration in the design and interpretation of discordant couple studies.

Herpes simplex virus type 2: epidemiology and management options in developing countries.

Genital herpes simplex virus type 2 (HSV2) is highly prevalent worldwide and an increasingly important cause of genital ulcer disease (GUD). Continued HSV2 transmission is facilitated by the large number of undiagnosed cases, the frequency of atypical disease and the occurrence of asymptomatic shedding. The lack of easy, affordable diagnostic methods and specific antiviral treatment in countries with low and middle income is of great concern, given the ability of GUD to enhance HIV transmission and acquisition. With rising HSV2 prevalence contributing to an increase in the proportion of GUD attributed to genital herpes in high-HIV prevalence settings, a safe and effective HSV vaccine is urgently needed. Meanwhile, multifaceted interventions are required to improve recognition of genital herpes, to prevent its spread and also to prevent its potential to promote HIV transmission in developing countries.

Acyclovir prophylaxis for pregnant women with a known history of herpes simplex virus: a cost-effectiveness analysis.

OBJECTIVE: Previous literature has shown acyclovir to be cost-effective as prophylaxis for women with genital symptomatic herpes simplex virus infection recurrence during pregnancy. We extend this analysis by adding quality-adjusted life year measurements and considering women with a diagnosed history of herpes simplex virus infection but without recurrence in pregnancy. STUDY DESIGN: A decision analytic model was designed that compared acyclovir prophylaxis versus no acyclovir for women with a history of diagnosed genital herpes simplex virus infection but without recurrence in pregnancy. Sensitivity analysis and Monte Carlo simulations were performed to test for robustness. RESULTS: We found that 22,286 women must be treated to prevent 1 neonatal death, 8985 women to prevent 1 affected child, and 177 women to prevent 1 cesarean delivery. As compared with no acyclovir, acyclovir prophylaxis at 36 weeks of gestation saves approximately dollar 20 per person and increases total quality-adjusted life years by 0.01. In univariate sensitivity analysis, this result was robust to all reasonable probability and quality-adjusted life year estimates. Monte Carlo simulation demonstrated acyclovir to be cost-effective 100% of the time and cost saving >99% of the time. CONCLUSION: Acyclovir prophylaxis versus no treatment for pregnant women with a diagnosed history of genital herpes simplex virus infection but without recurrence during pregnancy is cost-effective over a wide range of assumptions.

Type-specific screening for asymptomatic herpes infection in pregnancy: a decision analysis.

OBJECTIVE: To evaluate the merits of serum screening for herpes simple virus (HSV) in pregnant women with no history of prior HSV infection. DESIGN: Clinical decision analysis. POPULATION: Hypothetical cohort of pregnant women in first trimester with no clinical history of HSV infection. METHODS: We used decision analysis techniques to compare three strategies for antepartum screening for HSV in women with no history of infection: (1) universal screening; (2) targeted screening in women estimated to be at high risk for infection; and (3) current care (no screening). For the screening strategies, we considered screening at 35 weeks of gestation, with prophylactic antiviral therapy for seropositive women. For all women, we assumed caesarean delivery in the setting of symptomatic infection at delivery. We performed a literature review of English-language publications to derive probability estimates for the rate of HSV seropositivity in asymptomatic pregnant women, and the risks of symptomatic HSV infection and asymptomatic shedding at the time of delivery. We determined the modification of rates of viral shedding, symptomatic lesions and caesarean section with the use of prophylactic suppression therapy for seropositive women based on available data. We chose neonatal herpes with severe sequelae, neonatal death, as well as caesarean delivery as clinically relevant outcomes. MAIN OUTCOME MEASURES: Number of cases of neonatal death, neonatal HSV with severe sequelae, neonatal HSV with moderate sequelae, patients screened, patients treated and caesarean section with each strategy. RESULTS: Universal maternal screening reduced the total number of deaths and severe sequelae secondary to neonatal HSV. Universal screening required treatment of 3849 women to prevent one case of neonatal death or disease with severe sequelae from HSV. Targeted screening of high risk women treatment of 2277 women to prevent one death or case of severe disease. Universal screening reduced the rate of neonatal HSV attributable to recurrent HSV by 79.3%. Caesarean delivery was reduced with both screening strategies. We used one-way sensitivity analyses to evaluate the robustness of our model. CONCLUSIONS: Maternal screening reduced the number of cases of neonatal HSV. Screening also reduced the rate of caesarean delivery. However, employing universal screening will likely result in a significant expenditure of medical resources because the number needed to treat to avert a single case of neonatal herpes is high.

Targeting virological core groups: a new paradigm for controlling herpes simplex virus type 2 epidemics.

BACKGROUND: Classic modeling of sexually transmitted diseases has focused on modeling behavioral heterogeneity and designing epidemic control strategies targeted at behavioral core groups. METHODS: We analyzed a new mathematical model of herpes simplex virus type 2 (HSV-2) epidemics that includes virological core groups (i.e., groups of individuals with high rates of viral reactivation) and suggest a new paradigm for epidemic control. We used our model, in conjunction with virological data, to determine the potential role of virological core groups in contributing to transmission and the effect that daily antiviral therapy (DAT) could have on reducing transmission if virological core groups were targeted. RESULTS: We estimated that a virological core group (11% of infected individuals) can cause a disproportionately large percentage (44%) of new infections and that a median of only 6.4 person-years of DAT would be necessary to prevent 1 HSV-2 infection. We determined that relatively few individuals would need to receive DAT to substantially reduce the incidence of HSV-2 infection. CONCLUSION: Identifying and targeting individuals in the virological core group could be an effective and practical public health strategy for reducing transmission. Treating individuals who are high-frequency viral shedders should be evaluated as a strategy for reducing HSV-2 transmission.