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We recently reported that the risk of sexually acquired HIV-1 infection is increased significantly by variants in the gene encoding CD101, a protein thought to modify inflammatory responses. Using blood samples from individuals with and without these variants, we demonstrate that CD101 variants modify the prevalence of circulating inflammatory cell types and show that CD101 variants are associated with increased proinflammatory cytokine production by circulating T cells. One category of CD101 variants is associated with a reduced capacity of regulatory T cells to suppress T cell cytokine production, resulting in a reduction in the baseline level of immune quiescence. These data are supported by transcriptomics data revealing alterations in the intrinsic regulation of antiviral pathways and HIV resistance genes in individuals with CD101 variants. Our data support the hypothesis that CD101 contributes to homeostatic regulation of bystander inflammation, with CD101 variants altering heterosexual HIV-1 acquisition by facilitating increased prevalence and altered function of T cell subsets.

New tools are needed to support PrEP adherence for individuals at risk for HIV, including those that enable provision of real-time feedback. In a large, completed PrEP trial, adequate urine tenofovir levels measured by a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.

The World Health Organization has been involved in male contraceptive development for over 50 years. In line with its functions and mandate, World Health Organization works with diverse stakeholders to support research, develop norms and standards, engage member states, facilitate prequalification, introduction and scale up, measurement, and tracking of contraceptives. World Health Organization has a key role in galvanizing global efforts to ensure universal access to contraception services irrespective of income group. Regarding male contraceptive development, World Health Organization has provided technical leadership, supported early research, created and supported research centers, built research capacity in various countries, and standardized semen analysis procedures. In this paper, a detailed description is provided with examples across the various stages of male contraceptive development. Limited funding to World Health Organization is a key challenge. [ABSTRACT FROM AUTHOR]

BackgroundUnderstanding the absolute and relative risk of human immunodeficiency virus type 1 (HIV) acquisition during pregnancy and the postpartum period can inform HIV prevention strategies for women.MethodsWe used a complementary log-log model and data from 2751 HIV-serodiscordant couples to compare the probability of HIV acquisition among women per sex act during early pregnancy, late pregnancy, the postpartum period, and the nonpregnant period.ResultsAt total of 686 pregnancies were identified, and 82 incident HIV infections occurred. After adjustment for condom use, age, preexposure prophylaxis (PrEP) use, and HIV viral load, the per-act probability of HIV acquisition was higher in late pregnancy (adjusted relative risk [aRR], 2.82; P = .01) and the postpartum period (aRR, 3.97; P = .01) as compared to that during nonpregnant period. For a 25-year-old woman not taking PrEP, the HIV acquisition probability per condomless sex act with an HIV-infected male partner with a viral load of 10 000 copies/mL was 0.0011 (95% confidence interval [CI] 0.005-0.0019), 0.0022 (95% CI, 0.0004-0.0093), 0.0030 (95% CI, 0.0007-0.0108), and 0.0042 (95% CI, 0.0007-0.0177) during the nonpregnant period, early pregnancy, late pregnancy, and the postpartum period, respectively.ConclusionThe HIV acquisition probability per condomless sex act steadily increased during pregnancy and was highest during the postpartum period, suggesting that biological changes during pregnancy and the postpartum period increase HIV susceptibility among women.

BackgroundDaily oral tenofovir-based pre-exposure prophylaxis (PrEP) is high efficacious for HIV prevention among women with high adherence. However, the effect of abnormal vaginal microbiota on PrEP efficacy is of concern. We investigated whether bacterial vaginosis modified the efficacy of oral PrEP.MethodsWe used prospectively collected data from women in the Partners PrEP Study, a placebo-controlled trial of daily oral PrEP (either tenofovir monotherapy or a combination of tenofovir and emtricitabine) in HIV serodiscordant couples aged 18 years or older in Kenya and Uganda that showed high efficacy in women. We used Cox proportional hazards regression to assess PrEP efficacy among subgroups of women defined by bacterial vaginosis status based on yearly microscopy and Nugent scoring (0-3 indicated healthy microbiota, 4-6 intermediate, and 7-10 bacterial vaginosis). In separate efficacy analyses, we also investigated individual components of the score (ie, detection of Gardnerella vaginalis or Bacteroides spp and non-detection of Lactobacillus spp) as markers of abnormal microbiota.FindingsOf 1470 women (median age 33 years), 357 (24%) had bacterial vaginosis at enrolment. 45 women seroconverted to HIV. The HIV prevention efficacy of PrEP did not differ significantly among women with healthy microbiota (incidence 0·6 per 100 person years in PrEP group and 2·5 per 100 person-years in the placebo group; efficacy 76·55% [95% CI 43·09 to 90·37]), intermediate microbiota (HIV incidence 1·8 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 62·72% [95% CI -66·59 to 91·66]), or bacterial vaginosis (HIV incidence 0·9 per 100 person-years in the PrEP group and 3·5 per 100 person-years in the placebo group; efficacy 72·50% [95% CI 5·98 to 91·95]; pinteraction=0·871). PrEP efficacy was not significantly different between women with detected G vaginalis or Bacteroides spp morphotypes and those without these morphotypes (efficacy 68·62% vs 76·72%; pinteraction=0·652); or between those with Lactobacillus spp morphotypes and those without (70·48% vs 74·08%; pinteraction=0·86).InterpretationAmong African women with a high prevalence of bacterial vaginosis and high adherence to PrEP, the efficacy of daily oral PrEP for HIV prevention did not differ significantly among women with abnormal versus healthy vaginal microbiota as defined by Nugent score. These data are reassuring that oral PrEP delivery to women can continue without the need for concurrent testing for bacterial vaginosis or vaginal dysbiosis.FundingBill & Melinda Gates Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Institute of Allergy and Infectious Diseases.

IntroductionPreventing unintended pregnancies is important among all women, including those living with HIV. Increasing numbers of women, including HIV-positive women, choose progestin-containing subdermal implants, which are one of the most effective forms of contraception. However, drug-drug interactions between contraceptive hormones and efavirenz-based antiretroviral therapy (ART) may reduce implant effectiveness. We present four inter-related perspectives on this issue.DiscussionFirst, as a case study, we discuss how limited data prompted country-level guidance against the use of implants among women concomitantly using efavirenz in South Africa and its subsequent negative effects on the use of implants in general. Second, we discuss the existing clinical data on this topic, including the observational study from Kenya showing women using implants plus efavirenz-based ART had three-fold higher rates of pregnancy than women using implants plus nevirapine-based ART. However, the higher rates of pregnancy in the implant plus efavirenz group were still lower than the pregnancy rates among women using common alternative contraceptive methods, such as injectables. Third, we discuss the four pharmacokinetic studies that show 50-70% reductions in plasma progestin concentrations in women concurrently using efavirenz-based ART as compared to women not on any ART. These pharmacokinetic studies provide the biologic basis for the clinical findings. Fourth, we discuss how data on this topic have marked implications for both family planning and HIV programmes and policies globally.ConclusionThis controversy underlines the importance of integrating family planning services into routine HIV care, counselling women appropriately on increased risk of pregnancy with concomitant implant and efavirenz use, and expanding contraceptive method mix for all women. As global access to ART expands, greater research is needed to explore implant effectiveness when used concomitantly with newer ART regimens. Data on how HIV-positive women and their partners choose contraceptives, as well as information from providers on how they present and counsel patients on contraceptive options are needed to help guide policy and service delivery. Lastly, greater collaboration between HIV and reproductive health experts at all levels are needed to develop successful strategies to ensure the best HIV and reproductive health outcomes for women living with HIV.

BackgroundIntimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).MethodsWe analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage

BackgroundIntimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP).MethodsWe analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage

Background: Experiences of delayed conception and infertility have been reported among women. However, the concept of intersectionality is rarely utilised in studies of infertility, and it is particularly uncommon in research from low- and middle- income countries. Research question: What are the lived experiences of women with delayed conception in low to -middle income neighbourhoods of Delhi, India? Methods: This was a qualitative study (n = 35) that recruited women who had failed to conceive after 18 months of regular unprotected sexual intercourse. Data were collected between February and July 2021. Data were collected through focus group discussions in low income to middle income neighbourhoods of Delhi, India. Analysis identified themes related to intersecting axes of inequality. Results: The results showed that gender intersected with economics, masculinity, patriarchal norms and class to influence the experiences of women. The intersection of gender, economics and patriarchal norms compromised women's agency to be active generators of family income, and this dynamic was exacerbated by patrilocal residence. In addition, masculinity contributed to stigmatisation and blaming of women, due to the inaccurate perception that men did not contribute to a couple's infertility. The intersection of gender and social class in medical settings created barriers to women's access to medical information. Conclusion: Findings from this study provide representative examples of the variety of axes of inequality that shape women's experiences in the study setting. Although these findings may not be generalisable to all women who are experiencing delayed conception, they highlight a need for improved awareness and education on infertility, as well as a need to ensure the availability and accessibility of fertility care for couples in need. [ABSTRACT FROM AUTHOR]

Given recent updates to the postpartum contraception recommendations in the fifth edition of the Medical Eligibility Criteria for Contraceptive Use (MEC), published by the World Health Organization (WHO), the purpose of this qualitative study was to assess the extent to which national family planning policies in sub-Saharan African countries are in agreement with the WHO MEC, particularly with regard to postpartum contraceptive use. WHO headquarters sent questionnaires to country-level focal points to complete with their Ministry of Health counterparts. Between February and May 2016, 23 of 32 (72%) surveys were completed. All respondents reported that their countries had used the MEC document in the past, with most reporting that they had used the guidance as a reference (n = 20, 87%), for training purposes (n = 19, 83%), to change clinical practices (n = 17, 74%), and to develop national policies (n = 16, 70%). While many respondents (16, 70%) indicated their countries already include immediate postpartum intrauterine device insertion among breastfeeding women in their family planning policies, few reported currently allowing use of progestogen-only pills (n = 8, 35%) or implants (n = 8, 35%) during the immediate postpartum period (i.e., less than 48 hours after delivery) for breastfeeding women. A higher percentage of respondents indicated their countries allowed breastfeeding women the option of progestogen-only pills (n = 16, 70%) and implants (n = 13, 57%) between 48 hours and 6 weeks postpartum. Findings from this baseline assessment suggest that many countries may benefit from training and policy formulation support to adapt both new WHO MEC updates as well as existing recommendations from previous MEC revisions into national family planning guidelines.

BackgroundImmune 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).MethodsWe 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.ResultsGUD 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.ConclusionsInitiation 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.

BackgroundThe efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis.MethodsWe examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts.ResultsTransmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060).ConclusionsCondoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

: Introduction: As the range of effective HIV prevention options, including multiple biomedical tools, increases, there are many challenges to measuring HIV prevention efforts. In part, there is the challenge of varying prevention needs, between individuals as well as within individuals over time. The field of contraception faces many similar challenges, such as the range of prevention methods and changing contraceptive needs, and has developed many metrics for assessing contraceptive use at the program level, using frameworks that move beyond the HIV prevention cascade. We explore these similarities and differences between these two prevention fields and then discuss how each of these contraceptive metrics could be adapted to assessing HIV prevention. Discussion: We examined measures of initiation, coverage and persistence. Among measures of initiation, HIV Prevention–Post Testing would be a useful corollary to Contraceptive Use–Post Partum for a subset of the population. As a measure of coverage, both Net Prevention Coverage and HIV Protection Index (modelled off the Contraception Protection Index) may be useful. Finally, as a measure of persistence, Person‐Years of HIV Protection could be adapted from Couple‐Years Protection. As in contraception, most programs will not reach 100% on HIV prevention metrics but these metrics are highly useful for making comparisons. Conclusions: While we may not be able to perfectly capture the true population of who would benefit from HIV prevention, by building off the work of the contraceptive field to use and refine these metrics, we can assess and compare HIV prevention over time and across programs. Furthermore, these metrics can help us reach global targets, such as the 2025 UNAIDS Goals, and reduce HIV incidence., INTRODUCTION As highly effective HIV prevention methods—including treatment as prevention, HIV pre‐exposure prophylaxis (PrEP), condoms and male circumcision—have been available for more than a decade now, there are increasing challenges [...]

The World Health Organization (WHO) estimated that in 2016 the global annual incidence of chlamydia, gonorrhoea, trichomoniasis and syphilis among people 15 to 49 years of age was 376.4 million [...]

Problem In Burkina Faso, the coverage of services for family planning is low due to shortage of qualified health staff and limited access to services. Approach Following the launch of the Ouagadougou Partnership, an alliance to catalyse the expansion of family planning services, the health ministry created a consortium of family planning stakeholders in 2011. The consortium adopted a collaborative framework to implement a pilot project for task sharing in family planning at community and primary health-care centre levels in two rural districts. Stakeholders were responsible for their areas of expertise. These areas included advocacy; monitoring and evaluation; and capacity development of community health workers (CHWs) to offer oral and injectable contraceptives to new users and of auxiliary nurses and auxiliary midwives to provide implants and intrauterine devices. The health ministry implemented supportive supervision cascades involving relevant planning and service levels. Local setting In Burkina Faso, only 15% (2563/17 087) of married women used modern contraceptives in 2010. Relevant changes Adoption of new policies and clinical care standards expanded task sharing roles in family planning. The consortium trained a total of 79 CHWs and 124 auxiliary nurses and midwives. Between January 2017 and December 2018, CHWs provided injectables to 3698 new users, and auxiliary nurses or midwives provided 726 intrauterine devices and 2574 implants to new users. No safety issues were reported. Lessons learnt The pilot project was feasible and safe, however, financial constraints are hindering scale-up efforts. Supportive supervision cascades were critical in ensuring success. Probleme Au Burkina Faso, la couverture des services de planification familiale est faible, en raison de la penurie de personnel de sante qualifie et de l'acces limite a ces services. Approche Suite au lancement du Partenariat de Ouagadougou, alliance destinee a accelerer l'expansion des services de planification familiale, le ministere de la Sante a cree en 2011 un consortium d'acteurs de la planification familiale. Ce consortium a adopte un cadre collaboratif pour mettre en reuvre un projet pilote visant a partager les taches de planification familiale, aux niveaux de la communaute et des centres de soins primaires, dans deux districts ruraux. Les differents acteurs etaient responsables de leurs domaines d'expertise, parmi lesquels la sensibilisation, le suivi et revaluation, ainsi que le renforcement des competences des agents de sante communautaires, afin de proposer des contraceptifs oraux et injectables a de nouvelles utilisatrices, et des aides-soignants et sages-femmes auxiliaires, dans le but de poser des implants et des dispositifs intra-uterins. Le ministere de la Sante a mis en place des structures d'encadrement faisant intervenir les niveaux concernes de planification et de services. Environnement local Au Burkina Faso, seules 15% (2563/17 087) des femmes mariees utilisaient des contraceptifs modernes en 2010. Changements significatifs L'adoption de nouvelles politiques et de nouveaux standards de soins a elargi les roles de partage des taches en matiere de planification familiale. Le consortium a forme un total de 79 agents de sante communautaires et de 124 aides-soignants et sagesfemmes auxiliaires. Entre janvier 2017 et decembre 2018, les agents de sante communautaires ont delivre des contraceptifs injectables a 3698 nouvelles utilisatrices, et les aides-soignants et sages-femmes auxiliaires ont pose 726 dispositifs intra-uterins et 2574 implants a de nouvelles utilisatrices. Aucun probleme de securite n'a ete signale. Lecons tirees Ce projet pilote etait realisable et sur; cependant, des contraintes financieres entravent les efforts devolution. Les structures d'encadrement ont ete essentielles a la reussite de ce projet. Situacion En Burkina Faso, la cobertura de los servicios de planificacion familiar es baja debido a la escasez de personal sanitario cualificado y al acceso limitado a los servicios. Enfoque Tras la puesta en marcha de Ouagadougou Partnership (la Asociacion de Uagadugu), una alianza para promover la expansion de los servicios de planificacion familiar, el Ministerio de Salud creo en 2011 un consorcio de interesados en la planificacion familiar. El consorcio adopto un marco de colaboracion para ejecutar un proyecto piloto de distribucion de tareas en materia de planificacion familiar a nivel comunitario y de centros de atencion primaria de la salud en dos distritos rurales. Las partes interesadas eran responsables de sus areas de especializacion. Estas areas incluian la promocion, la vigilancia y la evaluacion, y el desarrollo de la capacidad de los trabajadores sanitarios de la comunidad (community health workers, CHW) para ofrecer anticonceptivos orales e inyectables a los nuevos usuarios, asi como de los enfermeros auxiliares y las parteras auxiliares para proporcionar implantes y dispositivos intrauterinos. El Ministerio de Salud implemento cascadas de supervision de apoyo que involucran niveles relevantes de planificacion y servicio. Marco regional En Burkina Faso, solamente el 15 % (2 563/17 087) de las mujeres casadas utilizaron anticonceptivos modernos en 2010. Cambios importantes La adopcion de nuevas politicas y estandares de atencion clinica expandio la distribucion de tareas en la planificacion familiar. El consorcio capacito a un total de 79 CHW y 124 enfermeros y parteras auxiliares. Entre enero de 2017 y diciembre de 2018, los CHW administraron inyectables a 3 698 nuevas usuarias, y los enfermeros auxiliares o parteras suministraron 726 dispositivos intrauterinos y 2 574 implantes a las nuevas usuarias. No se informo de ningun problema de seguridad. Lecciones aprendidas El proyecto piloto era viable y seguro; sin embargo, las limitaciones financieras estan obstaculizando los esfuerzos de ampliacion. Las cascadas de supervision de apoyo fueron fundamentales para garantizar el exito., Introduction Family planning is recognized as a cost-effective intervention for curbing issues within sexual and reproductive health, improving women's status and increasing women's capacities to contribute to family income. (1,2) [...]

Bacterial vaginosis (BV) is a common vaginal syndrome associated with altered microflora that increases the risk of preterm delivery and acquisition of sexually transmitted diseases. The cause of BV is unknown although toll-like receptors (TLRs), that are central to innate immune responses, may be important. We evaluated associations between TLR SNPs and BV among HIV-1 infected and uninfected African women. Logistic regression was used to assess associations between SNPs (N=99) in TLRs 2-4, 7-9 and BV (as classified by Nugent's criteria). Among HIV-1 uninfected women, TLR7 rs5743737 and TLR7 rs1634323 were associated with a decreased risk of BV, whereas TLR7 rs179012 was associated with an increased risk. TLR2 SNP rs3804099 was associated with a decreased risk of BV among HIV-1 infected women. Our findings indicate that there may be differences in TLR association with BV among HIV-1 infected and HIV-1 uninfected women.