Jillian Pintye

Scaling up access to oral rehydration solution for diarrhea: Learning from historical experience in low- and high-performing countries

Aim This paper aims to identify factors that systematically predict why some countries that have tried to scale up oral rehydration solution (ORS) have succeeded, and others have not. Methods We examined ORS coverage over time, across countries, and through case studies. We conducted expert interviews and literature and data searches to better understand the history of ORS scale–up efforts and why they failed or succeeded in nine countries. We used qualitative, pairwise (or three–country) comparisons of geographically or otherwise similar countries that had different outcomes in terms of ORS scale–up. An algorithm was developed which scored country performance across key supply, demand and financing activities to quantitatively assess the scale–up efforts in each country. Results The vast majority of countries have neither particularly low nor encouragingly high ORS use rates. We observed three clearly identifiable contrasts between countries that achieved and sustained high ORS coverage and those that did not. Key partners across sectors have critical roles to play to effectively address supply– and demand–side barriers. Efforts must synchronize demand generation, private provider outreach and public sector work. Many donor funds are either suspended or redirected in the event of political instability, exacerbating the health challenges faced by countries in these contexts. We found little information on the cost of scale–up efforts. Conclusions We identified a number of characteristics of successful ORS scale–up programs, including involvement of a broad range of key players, addressing supply and demand generation together, and working with both public and private sectors. Dedicated efforts are needed to launch and sustain success, including monitoring and evaluation plans to track program costs and impacts. These case studies were designed to inform programmatic decision–making; thus, rigorous academic methods to qualitatively and quantitatively evaluate country ORS scale–up programs might yield additional, critical insights and confirm our conclusions.

PrEP as Peri-conception HIV Prevention for Women and Men

Daily oral tenofovir (TDF)-based pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy and recommended for men and women with substantial risk of HIV acquisition. The peri-conception period, the stage prior to pregnancy when condom use is necessarily reduced, has elevated HIV risk that can be mitigated by PrEP use. Data from a randomized trial suggest that peri-conception PrEP use by HIV-seronegative women does not increase the risk of pregnancy loss, birth defects or congenital anomalies, preterm birth, or infant growth faltering. Women considering PrEP use throughout pregnancy must weigh the known increased risk of HIV acquisition with unknown risks of drug effects on infant growth. PrEP has been used safely by HIV-seronegative men with HIV-seropositive female partners who have become pregnant. As an effective user-controlled HIV prevention strategy, PrEP offers autonomy and empowerment for HIV prevention and can be recommended alongside antiretroviral therapy, fertility screening, vaginal self-insemination, intercourse timed to peak fertility, medically assisted reproduction, and other safer conception strategies to provide multiple options. The integration of PrEP into safer conception programs is warranted and will safely reduce HIV transmission to women, men, and children during the peri-conception period.

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 efficacy 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-significant 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 confirmed, these results suggest that medical male circumcision could substantially reduce incidence of syphilis and its sequelae. FUNDING Bill & Melinda Gates Foundation and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

A Risk Assessment Tool for Identifying Pregnant and Postpartum Women Who May Benefit From Preexposure Prophylaxis

Background A human immunodeficiency virus (HIV) risk assessment tool for pregnant women could identify women who would most benefit from preexposure prophylaxis (PrEP) while minimizing unnecessary PrEP exposure. Methods Data from a prospective study of incident HIV among pregnant/postpartum women in Kenya were randomly divided into derivation (n = 654) and validation (n = 650) cohorts. A risk score was derived using multivariate Cox proportional hazards models and standard clinical prediction rules. Ability of the tool to predict maternal HIV acquisition was assessed using the area under the curve (AUC) and Brier score. Results The final risk score included the following predictors: having a male partner with unknown HIV status, number of lifetime sexual partners, syphilis, bacterial vaginosis (BV), and vaginal candidiasis. In the derivation cohort, AUC was 0.84 (95% confidence interval [CI], .72-.95) and each point increment in score was associated with a 52% (hazard ratio [HR], 1.52 [95% CI, 1.32-1.76]; P < .001) increase in HIV risk; the Brier score was 0.11. In the validation cohort, the score had similar AUC, Brier score, and estimated HRs. A simplified score that excluded BV and candidiasis yielded an AUC of 0.76 (95% CI, .67-.85); HIV incidence was higher among women with risk scores >6 than with scores ≤6 (7.3 vs 1.1 per 100 person-years, respectively; P < .001). Women with simplified scores >6 accounted for 16% of the population but 56% of HIV acquisitions. Conclusions A combination of indicators routinely assessed in antenatal clinics was predictive of HIV risk and could be used to prioritize pregnant women for PrEP.

Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya

Background. Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. Materials and Methods. We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. Results. Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (−0.8 versus −0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. Conclusion. Maternal TDF use did not adversely affect infant growth compared to other regimens.

Brief Report: Lopinavir Hair Concentrations are the Strongest Predictor of Viremia in Hiv-infected Asian Children and Adolescents on Second-line Antiretroviral Therapy

Background: Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir (LPV) levels on viremia among youth on second-line ART. Methods: We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/mL) at least 24 weeks after switch to LPV-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of LPV were measured through liquid chromatography/tandem mass spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models. Results: Overall, 244 children met the inclusion criteria for the present analysis. Approximately half (55%) were boys and the median age 10 years [interquartile range (IQR) 7–13]; 40% were older than 11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146–547) cells/mm3 and median HIV-RNA level was 5.0 (IQR 4.3–5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1–5) hair samples were collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher LPV hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/mL adjusted odds ratio = 0.41 per doubling in hair concentration, 95% confidence interval: 0.29 to 0.58, P < 0.001; HIV-RNA >1000 copies/mL, adjusted odds ratio = 0.54, 95% confidence interval: 0.45 to 0.65, P < 0.001). Conclusions: Hair concentrations predict viremia among children with HIV on second-line ART and could guide clinical decisions for this population.

Patient-Delivered Partner Treatment for Chlamydia, Gonorrhea, and Trichomonas Infection Among Pregnant and Postpartum Women in Kenya.

Background Patient-delivered partner treatment (PDPT) for sexually transmitted infections (STIs) increases rates of partner treatment and decreases reinfection, but has not been evaluated during pregnancy. Methods This prospective cohort was nested within a larger study of peripartum HIV acquisition. Participants with microbiologic diagnosis of Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis were screened for participation. Questionnaires were administered to determine PDPT acceptability and barriers. Women were reassessed at least 30 days to determine partner treatment and reinfection. Women whose partners did or did not receive PDPT were compared. Results One hundred twelve (22.2%) women in the parent cohort had a treatable STI; 78 within the PDPT study period, of whom 66 were eligible and 59 (89.3%) accepted PDPT. Fifty-one women had PDPT outcome data, 37 (73%) of whom reported partners treated with PDPT. Fourteen women (27%) refused or did not deliver partner treatment. Median age was 22 years (interquartile range, 20–26 years) and 88% were married. Compared with women who delivered PDPT, those who did not were more likely to have a partner living far away (23% vs. 0%, P = 0.004) and to report current intimate partner violence (14% vs. 0%, P = 0.02). Reported PDPT barriers included fear of partners anger/abuse (5%) and accusations of being STI source (5%). Conclusion Patient-delivered partner treatment was acceptable and feasible for pregnant/postpartum Kenyan women and may reduce recurrent STIs in pregnancy.

Male partner circumcision associated with lower Trichomonas vaginalis incidence among pregnant and postpartum Kenyan women: a prospective cohort study

Objective Trichomonas vaginalis is the worlds most common curable STI and has implications for reproductive health in women. We determined incidence and correlates of T. vaginalis in an HIV-uninfected peripartum cohort. Methods Women participating in a prospective study of peripartum HIV acquisition in Western Kenya were enrolled during pregnancy and followed until 9 months post partum. T. vaginalis was assessed every 1–3 months using wet mount microscopy. Correlates of incident T. vaginalis were determined using Cox proportional hazards models. Results Among 1271 women enrolled, median age was 22 years (IQR 19–27) and gestational age was 22 weeks (IQR 18–26); most (78%) were married and had uncircumcised male partners (69%). Prevalent T. vaginalis was detected in 81 women (6%) at enrolment. Among women without T. vaginalis at enrolment, 112 had T. vaginalis detected during 1079 person-years of follow-up (10.4 per 100 person-years). After adjustment for socio-economic factors, male partner circumcision status, pregnancy status and other STIs, T. vaginalis incidence was higher during pregnancy than post partum (22.3 vs 7.7 per 100 person-years, adjusted HR (aHR) 3.68, 95% CI 1.90 to 7.15, p<0.001). Women with circumcised male partners had a 58% lower risk of incident T. vaginalis compared with women with uncircumcised partners (aHR 0.42, 95% CI 0.23 to 0.76, p=0.004). Employed women had lower risk of incident T. vaginalis than unemployed women (aHR 0.49, 95% CI 0.31 to 0.79, p=0.003); recent STI was associated with increased T. vaginalis risk (aHR 2.97, 95% CI 1.49 to 5.94, p=0.002). Conclusions T. vaginalis was relatively common in this peripartum cohort. Male circumcision may confer benefits in preventing T. vaginalis.

Maternal Tenofovir Disoproxil Fumarate Use During Pregnancy Is Not Associated With Adverse Perinatal Outcomes Among HIV-infected East African Women: A Prospective Study

Background Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and pre-exposure prophylaxis regimens. We evaluated the relationship between adverse perinatal outcomes and prenatal TDF use. Methods Longitudinal data were analyzed from human immunodeficiency virus (HIV)-infected women who became pregnant during 2 HIV prevention studies conducted among HIV-serodiscordant couples in Kenya and Uganda. Pregnancies included were singleton, not terminated by an induced abortion, and had documented 3-drug ART use. Multivariate generalized estimating equation models were used to determine the association of prenatal TDF and perinatal outcomes. Results The most frequent ART regimens were TDF/3TC/EFV (39%) and AZT/3TC/NVP (34%); 49% of pregnancies had prenatal TDF exposure and 6% used a protease inhibitor. Neonatal death, preterm birth, and pregnancy loss occurred in 2%, 8%, and 12% of pregnancies, respectively. No differences were observed between pregnancies with and without exposure to TDF in the frequency of pregnancy loss (adjusted prevalence rate ratio [aPRR] 1.19, P = .8) or neonatal death (aPRR 0.68, P = .6). Preterm birth occurred less frequently among pregnancies exposed to TDF (aPRR, 0.34, P = .02). Conclusion Maternal TDF use did not adversely affect perinatal outcomes.

Sexually transmitted infections during pregnancy and subsequent risk of stillbirth and infant mortality in Kenya: a prospective study

Objectives We evaluated the relationship of sexually transmitted infections (STIs) and genital infections during pregnancy and subsequent risk for infant mortality and stillbirth. Methods This was a nested longitudinal analysis using data from a study of peripartum HIV acquisition in Kenya. In the parent study, HIV-uninfected women were enrolled during pregnancy and followed until 9 months postpartum. For this analysis, women who tested positive for HIV at any point, had a non-singleton pregnancy or a spontaneous abortion <20 weeks were excluded. At enrolment, laboratory methods were used to screen for bacterial vaginosis (BV), vaginal yeast, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV). Syphilis was diagnosed using rapid plasma reagin testing and genital ulcer disease (GUD) identified by clinical examination. Treatment of laboratory-confirmed STIs and syndromic management was provided per Kenyan national guidelines. Predictors of stillbirth and infant mortality were determined using logistic regression and Cox proportional hazards models. Results Overall, among 1221 women, 55% had STIs or genital infections detected: vaginal yeast (25%), BV (22%), TV (6%), CT (5%), NG (2%) and syphilis (1%). Among women with STIs/genital infections (n=592), 34% had symptoms. Overall, 19/1221 (2%) women experienced stillbirths. Among 1202 live births, 34 infant deaths occurred (incidence 4.0 deaths per 100 person-years, 95% CI 2.8 to 5.5). After adjustment for maternal age, education and study site, stillbirth was associated with maternal GUD (adjusted OR=9.19, 95% CI1.91 to 44.35, p=0.006). Maternal NG was associated with infant mortality (adjusted HR=3.83, 95% CI1.16 to 12.68, p=0.028); there was some evidence that maternal CT was associated with infant mortality. Stillbirth or infant mortality were not associated with other genital infections. Conclusions STIs and genital infections were common, frequently asymptomatic and some associated with stillbirth or infant mortality. Expediting diagnosis and treatment of STIs in pregnancy may improve infant outcomes.