Concomitant contraceptive implant and efavirenz use in women living with HIV: perspectives on current evidence and policy implications for family planning and HIV treatment guidelines.

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

Supporting early career health investigators in Kenya: A qualitative study of HIV/AIDS research capacity building

Introduction: strategies to transfer international health research training programs to sub-Saharan African institutions focus on developing cadresof local investigators who will lead such programs. Using a critical  leadership theory framework, we conducted a qualitative study of one program to understand how collaborative training and research can support early career investigators in Kenya toward the program transfer goal.Methods: We used purposive sampling methods and a semi-structured protocol to conduct in-depth interviews with US (N=5) and Kenyan (N=5)independent investigators. Transcripts were coded using a two-step  process, and then compared with each other to identify major themes.Results: A limited local research environment, funding needs and research career mentorship were identified as major influences on early career researchers. Institutional demands on Kenyan faculty to teach rather than complete research restricted investigators' ability to develop research careers. This was coupled with lack of local funding to support research. Sustainable collaborations between Kenyan, US and other international investigators were perceived to mitigate these challenges and support early career investigators who would help build a robust local research environment for training. Conclusion: mutually beneficial collaborations between Kenyan and US investigators developed during training mitigate these challenges and build a supportive research environment for training. In these collaborations, early career investigators learn how to navigate the complex international research environment to build local HIV research capacity.Shared and mutually beneficial resources within international research collaborations are required to support early career investigators and plans to transfer health research training to African institutions

The influence of host and pathogen genotypes on symptom severity in banana streak disease

Banana is the fourth most important food crop worldwide. However, its production has been threatened by banana streak disease, caused by banana streak virus (BSV). Despite this situation, little is known about the inter-relationships between symptom severity and cultivar/virus genotypes. Symptom severity assessment for sixty five symptomatic samples was carefully done. The rolling circle amplification technique was used to identify the virus species (isolate) infecting each sample. The Mysore virus isolates (BSMysV) and the banana cultivars containing the balbisiana (B) component were associated with the most severe banana streak disease symptoms.Key words: Banana streak disease, symptom severity, banana streak virus (BSV) isolate, rolling circle amplification

Hormonal contraception and HIV acquisition among women : an updated systematic review

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Disclaimer The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention, the World Health Organization, or other institutions with which the authors are affiliated. Competing interests MIR reports personal fees from Merck (contraceptive implant trainer) and Bayer (IUD trainer), outside the submitted work. TC, JK and PS were members of the ECHO trial consortium, and JK and PS were part of the writing group for the ECHO trial results. All of the authors participated in the 2019 WHO Guideline Development Group (GDG) process which assessed recommendations on contraception for women at high risk of HIV. Patient consent for publication Not required. Provenance and peer review Not commissioned; externally peer reviewed. Contributors KC, PH, TC, PS and JK were coauthors on the previous systematic review and contributed to the planning of this updated review. KC, PH and TC conducted the literature search, screening, and risk of bias assessment. MIR conducted the meta-analysis. KC wrote the first draft of the manuscript. All authors contributed to subsequent drafts and approved of the final manuscript.Peer reviewedPublisher PD

Maternal valacyclovir and infant cytomegalovirus acquisition: a randomized controlled trial among HIV-infected women.

Background Studies in HIV-1-infected infants and HIV-1-exposed, uninfected infants link early cytomegalovirus (CMV) acquisition with growth delay and cognitive impairment. We investigated maternal valacyclovir to delay infant acquisition of CMV. Methods Pregnant women with HIV-1, HSV-2 and CD4 count >250 cells/µl were randomized at 34 weeks gestation to 500 mg twice-daily valacyclovir or placebo for 12 months. Maternal CMV DNA was measured in plasma at 34 weeks gestation, in cervical secretions at 34 and 38 weeks gestation, and in breast milk at 7 postpartum timepoints; infant CMV DNA was measured in dried blood spots at 8 timepoints including birth. Results Among 148 women, 141 infants were compared in intent-to-treat analyses. Maternal and infant characteristics were similar between study arms. Infant CMV acquisition did not differ between study arms, with 46/70 infants (66%) in placebo arm and 47/71 infants (66%) in the valacyclovir arm acquiring CMV; median time to CMV detection did not differ. CMV DNA was detected in 92% of 542 breast milk specimens with no difference in CMV level between study arms. Change in cervical shedding of CMV DNA between baseline and 38 weeks was 0.40-log greater in the placebo arm than the valacyclovir arm (p = 0.05). Conclusions In this cohort of HIV-1-seropositive mothers, two-thirds of infants acquired CMV by one year. Maternal valacyclovir had no effect on timing of infant CMV acquisition or breast milk CMV viral loads, although it modestly reduced cervical CMV shedding. Maternal prophylaxis to reduce infant CMV acquisition warrants further evaluation in trials with antiviral agents

Sexually Transmitted Infections among HIV-1-Discordant Couples

INTRODUCTION:More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS:HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS:Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01), and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01) and those with low education (OR = 3.00; P<0.01). Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01). CONCLUSIONS:Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission. TRIAL REGISTRATION:ClinicalTrials.gov NCT00194519

Male Perspectives on Incorporating Men into Antenatal HIV Counseling and Testing

Male partner involvement in antenatal voluntary HIV counseling and testing (VCT) has been shown to increase uptake of interventions to reduce the risk of HIV transmission in resource-limited settings. We aimed to identify methods for increasing male involvement in antenatal VCT and determine male correlates of accepting couple counseling in these settings.We invited women presenting to a Nairobi antenatal clinic to return with their male partners for individual or couples VCT. Male attitudes towards VCT and correlates of accompanying female partners to antenatal clinic and receiving couple counseling were determined. Of 1,993 women who invited their partner, 313 (16%) returned with their partners to ANC. Men attending antenatal clinic were married (>99%), employed (98%), and unlikely to report prior HIV testing (14%). Wanting an HIV test (87%) or health information (11%) were the most commonly cited reasons for attending. Most (95%) men who came to antenatal clinic accepted HIV testing and 39% elected to receive counseling as a couple. Men who received counseling with partners were younger, had fewer children, and were less knowledgeable about prevention of mother-to-child HIV transmission (PMTCT) than those who received counseling individually (p<0.05). Only 27% of men stated they would prefer HIV testing at a site other than the ANC. There was agreement between male and female reports for sociodemographic characteristics; however, men were more likely to report HIV preventive behaviors and health communication within the partnership than their partners (p<0.05).Offering VCT services to men at antenatal clinic with options for couple and individual counseling is an important opportunity and acceptable strategy for increasing male involvement in PMTCT and promoting male HIV testing

An updated systematic review of epidemiological evidence on hormonal contraceptive methods and HIV acquisition in women

We are grateful to Sharon Achilles for her thoughtful input related to describing potential biological mechanisms, and to all study investigators who provided additional information about their analyses. WHO provided support for the writing of this systmatic review and for the writing group to attend a working meeting in Geneva, Switzerland in October 2015. D.J.W. was partially funded by NIH DP2-HD-08-4070. The review was conducted independently of the WHO guidance development process; and conclusions represent the independent opinions of the authors. The findings and conclusions in this article do not necessarily reflect the positions and policies of the donor. Role of authors: The World Health Organization (J.N.K. and P.S.S.) initiated the idea to conduct this systematic review update. C.B.P. led the conduct of the systematic review, including conducting the systematic literature search and drafting the manuscript. C.B.P., K.M.C., and P.C.H. screened titles, abstracts, and full-text manuscripts to determine study inclusion. S.J.P. conducted the statistical meta-analysis. All coauthors (C.B.P., K.M.C., P.C.H., S.J.P., T.C., J.N.K., D.J.W., and P.S.S.) participated in framing the study question, developing the quality criteria, abstracting study information and assessing study quality, interpreting the data, and contributing to the writing and editing of the manuscript. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official positions of the Guttmacher Institute, the Centers for Disease Control and Prevention, the World Health Organization, the National Institutes of Health, or other institutions with which the authors are affiliated.Peer reviewedPublisher PD