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Background: Use of SMS for data collection is expanding, but coverage, bias, and logistical constraints are poorly described., Objective: The aim of this study is to assess the use of SMS to capture clinical outcomes that occur at home and identify potential biases in reporting compared to in-person ascertainment., Methods: In the PrEP Implementation in Young Women and Adolescents program, which integrated pre-exposure prophylaxis (PrEP) into antenatal care, postnatal care, and family planning facilities in Kisumu County, Kenya, HIV-negative women 14 years of age or older were offered oral HIV self-tests (HIVSTs) to take home to male partners. Women that brought a phone with a Safaricom SIM to the clinic were offered registration in an automated SMS system (mSurvey) to collect information on HIVST outcomes. Women were asked if they offered the test to their male partners, and asked about the test process and results. HIVST outcomes were collected via SMS (sent 2.5 weeks later), in-person (if women returned for a follow-up scheduled 1 month later), or using both methods (if women initiated PrEP, they also had scheduled follow-up visits). The SMS prompted women to reply at no charge. HIVST outcomes were compared between women with scheduled follow-up visits and those without (follow-up visits were only scheduled for women who initiated PrEP). HIVST outcomes were also compared between women reporting via SMS and in-person., Results: Among 2123 women offered HIVSTs and mSurvey registration, 486 (23.89%) accepted HIVSTs, of whom 359 (73.87%) were eligible for mSurvey. Additionally, 76/170 (44.7%) women with scheduled follow-up visits and 146/189 (77.3%) without scheduled follow-up visits registered in mSurvey. Among the 76 women with scheduled follow-ups, 62 (82%) had HIVST outcomes collected: 19 (31%) in-person, 20 (32%) by SMS, and 23 (37%) using both methods. Among the 146 women without scheduled visits, 87 (59.6%) had HIVST outcomes collected: 3 (3%) in-person, 82 (94%) by SMS, and 2 (2%) using both methods. SMS increased the collection of HIVST outcomes substantially for women with scheduled follow-up visits (1.48-fold), and captured 82 additional reports from women without scheduled follow-up visits. Among 222 women with reported HIVST outcomes, frequencies of offering partners the HIVST (85/95, 89% in-person vs 96/102, 94% SMS; P=.31), partners using the HIVST (83/85, 98% vs 92/96, 96%; P=.50), women using HIVST with partners (82/83, 99% vs 91/92, 99%; P=.94), and seeing partner's HIVST results (82/83, 99% vs 89/92, 97%; P=.56) were similar between women reporting in-person only versus by SMS only. However, frequency of reports of experiencing harm or negative reactions from partners was more commonly reported in the SMS group (17/102, 16.7% vs 2/85, 2%; P=.003). Barriers to the SMS system registration included not having a Safaricom SIM or a functioning phone., Conclusions: Our results suggest that the use of SMS substantially improves completeness of outcome data, does not bias reporting of nonsensitive information, and may increase reporting of sensitive information.  ., (©Alison L Drake, Emily Begnel, Jillian Pintye, John Kinuthia, Anjuli D Wagner, Claire W Rothschild, Felix Otieno, Valarie Kemunto, Jared M Baeten, Grace John-Stewart. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 25.03.2020.)

Objectives: Recent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines., Methods: In this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1β., Results: Detection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01) , Eggerthella sp type 1 (p=0.04) , M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1β concentrations. Seven bacterial taxa ( D. micraerophilus , Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (β=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1β (β=0.96, 95% CI 0.19 to 1.74; p=0.016)., Conclusions: This study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation., Competing Interests: Competing interests: RSM receives research funding, paid to the University of Washington, from Hologic. TLF has a patent, Molecular Diagnosis of Bacterial Vaginosis, licensed to Becton Dickinson. SS, MMM, DAL and TLF report grants from the NIH during the conduct of the study. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Short message service (SMS) presents an opportunity to expand the reach of care and improve reproductive health outcomes. SMS could increase family planning (FP) use through education, support and demand generation. The purpose of this analysis is to determine the perspectives of potential FP users to inform design of SMS., Methods: We conducted focus group discussions (FGD) with HIV-infected women and in-depth interviews (IDI) with male partners and health care workers (HCW) at urban and rural clinics in Kenya to design SMS content for a randomized controlled trial., Results: Women and men indicated SMS could be used as a tool to discuss FP with their partners, and help decrease misconceptions about FP. Women stated SMS could make them more comfortable discussing sensitive topics with HCWs compared to in-person discussions. However, some women expressed concerns about FP SMS particularly if they used FP covertly or feared partner disapproval of FP use. These findings were common among women who had not disclosed their status. Providers viewed SMS as an important tool for tracking patients and clinical triage in conjunction with routine clinical visits., Conclusion: Our findings suggest that SMS has the potential to facilitate FP education, counselling, and interaction with HCWs around FP.

Background: Short birth intervals increase risk for adverse maternal and infant outcomes including preterm birth, low birth weight (LBW), and infant mortality. Although postpartum family planning (PPFP) is an increasingly high priority for many countries, uptake and need for PPFP varies in low- and middle-income countries (LMIC). We performed a systematic review and meta-analysis to characterize postpartum contraceptive use, and predictors and barriers to use, among postpartum women in LMIC., Methods: PubMed, EMBASE, CINAHL, PsycINFO, Scopus, Web of Science, and Global Health databases were searched for articles and abstracts published between January 1997 and May 2018. Studies with data on contraceptive uptake through 12 months postpartum in low- and middle-income countries were included. We used random-effects models to compute pooled estimates and confidence intervals of modern contraceptive prevalence rates (mCPR), fertility intentions (birth spacing and birth limiting), and unmet need for contraception in the postpartum period., Results: Among 669 studies identified, 90 were selected for full-text review, and 35 met inclusion criteria. The majority of studies were from East Africa, West Africa, and South Asia/South East Asia. The overall pooled mCPR during the postpartum period across all regions was 41.2% (95% CI: 15.7-69.1%), with lower pooled mCPR in West Africa (36.3%; 95% CI: 27.0-45.5%). The pooled prevalence of unmet need was 48.5% (95% CI: 19.1-78.0%) across all regions, and highest in South Asia/South East Asia (59.4, 95% CI: 53.4-65.4%). Perceptions of low pregnancy risk due to breastfeeding and postpartum amenorrhea were commonly associated with lack of contraceptive use and use of male condoms, withdrawal, and abstinence. Women who were not using contraception were also less likely to utilize maternal and child health (MCH) services and reside in urban settings, and be more likely to have a fear of method side effects and receive inadequate FP counseling. In contrast, women who received FP counseling in antenatal and/or postnatal care were more likely to use PPFP., Conclusions: PPFP use is low and unmet need for contraception following pregnancy in LMIC is high. Tailored counseling approaches may help overcome misconceptions and meet heterogeneous needs for PPFP.

Background: Data on utilisation of in-facility second-trimester abortion services are sparse. We describe temporal and geographical trends in utilisation of in-facility second-trimester abortion services across Mexico., Methods: We used 2007-2015 data from Mexico's Automated Hospital Discharge System (SAEH) to identify second-trimester abortive events (ICD O02-O08) in public hospitals across Mexico's 32 states. We described utilisation, calculated rates using population data, and used logistic regression to identify woman- and state-level factors (municipality-level marginalisation, state-level abortion law) associated with utilisation of second-trimester versus first-trimester services., Results: We identified 145 956 second-trimester abortions, or 13.4% of total documented hospitalizations for abortion between 2007 to 2015. The annual utilisation rate of second-trimester abortion remained constant, between 0.5 to 0.6 per 1000 women aged 15-44 years. Women living in highly marginalised municipalities had 1.43 higher odds of utilising abortions services in their second versus their first trimester, when compared with women in municipalities with low marginalisation (95% CI 1.18 to 1.73). Living in a state with a health or fetal anomaly exception to abortion restrictions was not associated with higher utilisation of second-trimester abortion services., Conclusions: Our results suggest there is a need for all types of second-trimester abortion services in Mexico. To improve health outcomes for Mexican women, especially the most vulnerable, access to safe second-trimester abortion services must be ensured through the implementation of current legal exceptions and renewed attention to the training of healthcare providers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Unmet need for contraception is high during the postpartum period, increasing the risk of unintended subsequent pregnancy. We developed a client facing mobile phone-based family planning (FP) decision aid and assessed acceptability, feasibility, and utility of the tool among health care providers and postpartum women., Methods: Semi-structured in-depth interviews (IDIs) were conducted among postpartum women (n = 25) and FP providers (n = 17) at 4 Kenyan maternal and child health clinics, 2 in the Nyanza region (Kisumu and Siaya Counties) and 2 in Nairobi. Stratified purposive sampling was used to enroll postpartum women and FP providers. Data were analyzed using an inductive content analysis approach by 3 independent coders, with consensual validation., Results: FP providers stated that the Interactive Mobile Application for Contraceptive Choice (iMACC) tool contained the necessary information about contraceptive methods for postpartum women and believed that it would be a useful tool to help women make informed, voluntary decisions. Most women valued the decision aid content, and described it as being useful in helping to dispel myths and misconceptions, setting realistic expectations about potential side effects and maintaining confidentiality. Both women and providers expressed concerns about literacy and lack of familiarity with smart phones or tablets and suggested inclusion of interactive multimedia such as audio or videos to optimize the effectiveness of the tool., Conclusions: The iMACC decision aid was perceived to be an acceptable tool to deliver client-centered FP counseling by both women and providers. Counseling tools that can support FP providers to help postpartum women make informed and individualized FP decisions in resource-limited settings may help improve FP counseling and contraceptive use in the postpartum period.

Background: Providing HIV self-tests to women for distribution to male partners may provide a unique opportunity to increase male partner and couples testing among women in HIV high-burden settings., Methods: Between November 2017 and June 2018, we offered self-tests for at-home couples or partner HIV testing to HIV-uninfected women seeking routine maternal and child health and family planning services at eight facilities in Kisumu, Kenya. Women accepting self-tests were offered at least two self-tests (OraQuick) to take to their partner(s) with instructions on use. HIV self-testing (HIVST) outcomes were evaluated using available programmatic data., Results: Overall, 3620 women were offered self-tests for at-home male partner HIV testing. The median age was 24 years (interquartile range 21-28) and 81% were in monogamous marriages. Overall, 1422 (39%) women reported having a partner of unknown HIV status, of whom 755 (53%) accepted self-tests. Among women with partners of unknown HIV status who declined self-tests (n = 667), 49% reported needing to consult their partner. Pregnant women were more likely to accept HIVST than nonpregnant women (prevalence ratio = 1.2, 95% confidence interval 1.0-1.4, P = 0.013). Self-testing outcomes were ascertained for 389 (44%) women who accepted self-tests. Among these women, 93% offered HIVSTs to their male partner; of these, 95% reported their male partners used the self-test and 99% used a self-test with their partner., Conclusion: Among women attending routine maternal and child health and family planning services who had male partners of unknown HIV status, over half accepted self-tests for partner testing. Most women with outcomes ascertained reported that male partners accepted and used self-tests and that couples testing occurred.

Objectives. To assess the effect of 2-way short message service (SMS) with a nurse on postpartum contraceptive use among individual women and couples. Methods. From 2016 to 2017, we conducted a randomized controlled trial at 2 public hospitals in western Kenya. We assigned eligible pregnant women to receive 2-way SMS with a nurse or no SMS, with the option to include male partners. We delivered automated family planning-focused SMS messages weekly until 6 months postpartum. Women and men receiving SMS could interact with nurses via SMS. In intention-to-treat analysis, we compared highly effective contraceptive (HEC) use at 6 months postpartum between groups using the χ 2 test. We used Poisson regression in adjusted analysis. Results. We randomized 260 women to 2-way SMS or control, and we enrolled 103 male partners. At 6 months postpartum, 69.9% women receiving SMS reported HEC use, compared with 57.4% in control (relative risk = 1.22; 95% confidence interval [CI] = 1.01, 1.47; P  = .04). In analysis adjusted for baseline demographic differences, the adjusted relative risk for HEC use in the SMS group was 1.26 (95% CI = 1.04, 1.52; P  = .02). Conclusions. Two-way SMS with a nurse, including optional male participation, increased postpartum contraceptive use. Trial Registration. ClinicalTrials.gov; identifier: NCT02781714.

Introduction: High maternal HIV incidence contributes substantially to mother-to-child HIV transmission (MTCT) in some settings. Since 2006, HIV retesting during the third trimester and breastfeeding has been recommended by the World Health Organization in higher prevalence (≥5%) settings to reduce MTCT. However, many countries lack clarity on when and how often to retest pregnant and postpartum women to optimize resources and service delivery. We reviewed and characterized national guidelines on maternal retesting based on timing and frequency., Methods: We identified 52 countries to represent variations in HIV prevalence, geography, and MTCT priority and searched available national MTCT, HIV testing and HIV treatment policies published between 2007 and 2017 for recommendations on retesting during pregnancy, labour/delivery and postpartum. Recommended retesting frequency and timing was extracted. Country HIV prevalence was classified as: very low (<1%), low (1% to 5%), intermediate (>5 to <15%) and high (≥15%). Women with unknown HIV status at delivery/postpartum were included in retesting guidelines., Results and Discussion: Overall, policies from 49 countries were identified; 51% from 2015 or later and most (n = 25) were from Africa. Four countries were high HIV prevalence, seven intermediate, sixteen low and twenty-two very low. Most (n = 31) had guidance on universal voluntary opt-out HIV testing at the first antenatal care (ANC) visit. Beyond the first ANC visit, the majority (78%, n = 38) had guidance on retesting; 22 recommended retesting all women with unknown/negative status, five only if unknown HIV status, three in pregnancy based on risk and eight combining these approaches. Retesting was universally recommended during pregnancy, labour/delivery, and postpartum for all high prevalence settings and four of seven intermediate prevalence settings. Five UNAIDS priority countries for EMTCT with low/very low HIV prevalence, but high/intermediate MTCT, had no guidance on retesting., Conclusions: Retesting guidelines for pregnant and postpartum women were ubiquitous in high prevalence countries and defined in some intermediate prevalence countries, but absent in some low HIV prevalence countries with high MTCT. Countries may require additional guidance on how to optimize maternal HIV testing and whether to prioritize retesting efforts or discontinue universal retesting based on HIV incidence. Research is needed to assess country-level guideline implementation and impact., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Involving male partners in family planning (FP) education and counseling may improve FP utilization and help meet couples' reproductive health needs in the postpartum period. We aimed to explore Kenyan men's and women's perspectives on an interactive short message service (SMS) approach to support postpartum FP decision-making, and inform intervention content for a randomized controlled trial (RCT)., Methods: We conducted four focus group discussions (FGD) among men (n = 35) and two among pregnant/postpartum women (n = 15) in western Kenya. Female participants were recruited at antenatal clinics; male participants were referred by antenatal attendees. FGDs included participant critique of pilot theory-based SMS messages. FGD transcripts were coded by two investigators and analyzed using an iterative, modified grounded theory approach. These data informed the intervention and RCT design, in which women had the option to refer male partners for trial enrollment., Results: Men strongly desired inclusion in FP programs, and frequently discussed negative relationship consequences of women's covert contraceptive use. Female and male participants voiced a variety of concerns about contraceptive side effects and potential harms, which were central to narratives of community influence on personal contraceptive choices. Most participants felt that receiving FP-focused SMS and including men would be beneficial. They perceived that SMS dialogue with a nurse about FP could reduce misperceptions and may stimulate communication within couples, thereby improving contraceptive access and continuation. Shared decision-making around FP within couple relationships, in consultation with clinicians, was highly valued., Conclusions: Health concerns about FP and limited couple communication are perceived contributors to postpartum unmet contraceptive need. With women's consent, the inclusion of male partners in FP services, and specifically in an mHealth SMS intervention, is acceptable and desired. Receiving SMS may trigger communication about postpartum FP within couples. SMS content should address contraceptive knowledge gaps, anticipated side effects and FP misperceptions, and allow for real-time method choice assistance.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the effect of short message service (SMS) communication on facility delivery, exclusive breastfeeding (EBF), and contraceptive use., Design: Mobile WACh was a three-arm unblinded individually randomised controlled trial., Setting: A public sector maternal child health (MCH) clinic in Nairobi, Kenya., Population: Three hundred women attending antenatal care were randomised, 100 to each arm, and followed for 24 weeks postpartum. Pregnant women, at least 14 years old with access to a mobile phone and able to read SMS were eligible for participation., Methods: Women were randomised (1:1:1) to receive one-way SMS versus two-way SMS with a nurse versus control. Weekly SMS content was tailored for maternal characteristics and pregnancy or postpartum timing., Main Outcome Measures: Facility delivery, EBF, and contraceptive use were compared separately between each intervention arm and the control arm by Kaplan-Meier analysis and chi-square tests using intent-to-treat analyses., Results: The overall facility delivery rate was high (98%) and did not differ by arm. Compared with controls, probability of EBF was higher in the one-way SMS arm at 10 and 16 weeks, and in the two-way SMS arm at 10, 16, and 24 weeks (P < 0.005 for all). Contraceptive use was significantly higher in both intervention arms by 16 weeks (one-way SMS: 72% and two-way SMS: 73%; P = 0.03 and P = 0.02 versus 57% control, respectively); however, this difference was not significant when correcting for multiple comparisons., Conclusion: One-way and two-way SMS improved EBF practices and early contraceptive use. Two-way SMS had an added benefit on sustained EBF, providing evidence that SMS messaging influences uptake of interventions that improve maternal and neonatal health., Source of Funding: Funding was provided by the National Institutes of Health (K12HD001264 to JAU, R01HD080460, K24HD054314 to GJS, and K01AI116298 to ALD), the National Science Foundation (Graduate Research Fellowship to TP and BD), as well as the University of Washington Global Center for Integrated Health of Women Adolescents and Children (Global WACh)., Tweetable Abstract: The Mobile WACh RCT demonstrates that SMS improved practice of exclusive breastfeeding and early postpartum contraception., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Background: Prevention of mother-to-child HIV transmission (PMTCT) relies on long-term adherence to antiretroviral therapy (ART). Mobile health approaches, such as text messaging (short message service, SMS), may improve adherence in some clinical contexts, but it is unclear what SMS content is desired to improve PMTCT-ART adherence., Objective: We aimed to explore the SMS content preferences related to engagement in PMTCT care among women, male partners, and health care workers. The message content was used to inform an ongoing randomized trial to enhance the PMTCT-ART adherence., Methods: We conducted 10 focus group discussions with 87 HIV-infected pregnant or postpartum women and semistructured individual interviews with 15 male partners of HIV-infected women and 30 health care workers from HIV and maternal child health clinics in Kenya. All interviews were recorded, translated, and transcribed. We analyzed transcripts using deductive and inductive approaches to characterize women's, partners', and health care workers' perceptions of text message content., Results: All women and male partners, and most health care workers viewed text messages as a useful strategy to improve engagement in PMTCT care. Women desired messages spanning 3 distinct content domains: (1) educational messages on PMTCT and maternal child health, (2) reminder messages regarding clinic visits and adherence, and (3) encouraging messages that provide emotional support. While all groups valued reminder and educational messages, women highlighted emotional support more than the other groups (partners or health care workers). In addition, women felt that encouraging messages would assist with acceptance of their HIV status, support disclosure, improve patient-provider relationship, and provide support for HIV-related challenges. All 3 groups valued not only messages to support PMTCT or HIV care but also messages that addressed general maternal child health topics, stressing that both HIV- and maternal child health-related messages should be part of an SMS system for PMTCT., Conclusions: Women, male partners, and health care workers endorsed SMS text messaging as a strategy to improve PMTCT and maternal child health outcomes. Our results highlight the specific ways in which text messaging can encourage and support HIV-infected women in PMTCT to remain in care, adhere to treatment, and care for themselves and their children., Trial Registration: ClinicalTrials.gov NCT02400671; https://clinicaltrials.gov/ct2/show/NCT02400671 (Archived by WebCite at http://www.webcitation.org/70W7SVIVJ)., (©Jade Fairbanks, Kristin Beima-Sofie, Pamela Akinyi, Daniel Matemo, Jennifer A Unger, John Kinuthia, Gabrielle O'Malley, Alison L Drake, Grace John-Stewart, Keshet Ronen. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 19.07.2018.)

Objective: Adolescent fertility rates are high in Kenya, and increase the risks of unintended repeat pregnancies and maternal and infant morbidity and mortality. Our objective was to examine knowledge, practices, and influences surrounding contraceptive access and use among Kenyan postpartum adolescents., Study Design: We conducted a mixed methods study (surveys and focus group discussions) with postpartum adolescents and family planning (FP) providers at two maternal and child health clinics in Kenya., Main Outcome Measures: Four focus group discussions (FGDs) were conducted with postpartum adolescents (stratified by age and site), and two FGDs were conducted with FP providers (stratified by site). Transcripts were analyzed for prevalent themes. The participants also completed individual surveys that were analyzed for contraceptive knowledge., Results: Adolescent contraceptive decision-making and use were shaped by social norms of adolescent sexual behaviour. Lack of FP knowledge, community misinformation, and insufficient counselling and time with providers all contributed to adolescent concerns about FP. However, as adolescents transitioned to motherhood, they felt more encouraged to use FP and had increased awareness of FP benefits., Conclusion: Both postpartum adolescents and providers felt delivery of FP services could be improved if providers had better training and counselling tools., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is growing evidence that mobile health (mHealth) approaches including short messaging service (SMS) can improve antiretroviral therapy (ART) adherence, but consensus is lacking regarding communication of HIV-related information. Most interventions to date have delivered SMS that do not overtly refer to HIV or ART in order to avoid risk of status disclosure. In formative work for an ongoing randomized controlled trial (RCT) evaluating one-way and two-way educational SMS for prevention of mother-to-child-transmission (PMTCT) adherence in Kenya, we conducted 10 focus group discussions (FGDs) with 87 HIV-infected peripartum women to determine desirability and preferred terminology of HIV-related content. SMS for the RCT were developed based on FGD findings. Roughly half of FGD participants supported receiving SMS containing overtly HIV-related terms, such as "HIV" and "medication", citing desire for detailed educational messages about ART and PMTCT. Those opposed to overt content expressed concerns about confidentiality. Many participants argued that acceptability of HIV-related content depended on the recipient's disclosure status and others' access to her phone. Based on these findings, both covert and overt SMS were developed for the RCT and participants who owned their phone or had disclosed their HIV status to anyone with access to their phone were able to choose one of three options: (1) covert SMS only, (2) overt SMS only in response to HIV-related questions from the participant, (3) overt SMS routinely, initiated by the study. Of the 825 participants in the RCT, 94% were eligible to receive overt SMS. Of these, 66% opted to receive routine overt SMS and 10% to receive participant-initiated overt SMS. These findings show there may be interest in overt HIV-related information by SMS when risk of status disclosure is low, and support use of messaging strategies that allows participant choice in HIV-related content while protecting against undesired disclosure.

Objective: The objective was to characterize uptake and correlates of effective contraceptive use postpartum., Study Design: We analyzed data from a national, cross-sectional evaluation of prevention of mother-to-child HIV transmission programs that enrolled women attending 6-week or 9-month infant immunization visits at 120 Kenyan maternal and child health clinics. We classified women who resumed sexual activity postpartum and did not desire a child within 2 years as having a need for family planning (FP)., Results: We included 955 (94%) of 1012 women 8-10 months postpartum in the analysis. Mean age was 25.8 years and 36% were primigravidas. By 9 months postpartum, 62% of all women used contraception and 59% used effective contraception [injectables, implants, intrauterine devices [IUDs], oral contraceptives [OCs] and tubal ligations]. Most contraceptive users (61%) used injectables, followed by implants (10%), OCs (6%), IUDs (4%) and condoms alone (2%). The majority (n=733, 77%) had a need for FP, and 67% of 733 women with FP need used effective contraception. Among women with a need for FP, effective contraception use was higher among those who discussed FP in postnatal care (PNC) than who did not discuss FP in PNC [prevalence ratio (PR) for PNC alone: 1.35, 95% confidence interval (CI): 1.16-1.58; PR for PNC and antenatal care (ANC): 1.42, 95% CI: 1.21-1.67; p=.001 for both]., Conclusions: Two thirds of postpartum women with a need for FP used effective contraception at 9 months postpartum, and use was associated with discussing FP during PNC., Implications: Integrating FP counseling in ANC/PNC could be an effective strategy to increase effective contraception use., (Published by Elsevier Inc.)

Background: Lifelong antiretroviral therapy (ART) (Option B+) is recommended for all HIV-infected pregnant/postpartum women, but high adherence is required to maximize HIV prevention potential and maintain maternal health. Mobile health (mHealth) interventions may provide treatment adherence support for women during, and beyond, the pregnancy and postpartum periods., Methods and Design: We are conducting an unblinded, triple-arm randomized clinical trial (Mobile WACh X) of one-way short message service (SMS) vs. two-way SMS vs. control (no SMS) to improve maternal ART adherence and retention in care by 2years postpartum. We will enroll 825 women from Nairobi and Western Kenya. Women in the intervention arms receive weekly, semi-automated motivational and educational SMS and visit reminders via an interactive, human-computer hybrid communication system. Participants in the two-way SMS arm are also asked to respond to a question related to the message. SMS are based in behavioral theory, are tailored to participant characteristics through SMS tracks, and are timed along the pregnancy/postpartum continuum. After enrollment, follow-up visits are scheduled at 6weeks; 6, 12, 18, and 24months postpartum. The primary outcomes, virological failure (HIV viral load ≥1000copies/mL), maternal retention in care, and infant HIV infection or death, will be compared in an intent to treat analysis. We will also measure ART adherence and drug resistance., Discussion: Personalized and tailored SMS to support HIV-infected women during and after pregnancy may be an effective strategy to motivate women to adhere to ART and remain in care and improve maternal and infant outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Objective: Trichomonas vaginalis is the world's 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 ., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Understanding sexual behaviors and vaginal practices of pregnant and breastfeeding women in sub-Saharan Africa is critical to inform HIV prevention strategies during these periods., Methods: HIV-uninfected women presenting for antenatal care in western Kenya were enrolled and followed through 36 weeks postpartum. Sexual behavior and vaginal practices were ascertained by structured questionnaires. Logistic regression was used to assess correlates of unprotected sex, vaginal washing, and vaginal drying., Results: Among 1252 women enrolled, 78.4% were married (of whom 15.1% were in polygamous unions), 1.4% had a known HIV-infected partner, and 33.6% had a partner of unknown HIV status. At enrollment, 58.5% reported sex in the past month (94.3% unprotected) and 4.5% reported forced sex. Odds of unprotected sex at enrollment was >11-fold higher in married than in unmarried women (P < 0.001) and lower among women who reported partners of unknown HIV status or HIV-infected compared with HIV-uninfected partners. Median time to postpartum resumption of sex was 7 weeks (interquartile range 4-12). Prevalence of unprotected sex in the past week increased from 6.6% to 60.0% between 2 and 36 weeks postpartum (P < 0.001). Vaginal washing was reported by 60.1% of women at enrollment and prevalence remained stable postpartum; vaginal drying was reported by 17.9% at enrollment and decreased to 6.1% at 36 weeks postpartum (P < 0.001). Vaginal washing and drying were associated with forced sex., Conclusions: High rates of unknown partner HIV status, polygamy, and less frequent condom use among pregnant/postpartum women underscore the need for female-controlled HIV prevention interventions. Vaginal washing and drying may present challenges to microbicide use.

Objective: The objective of this study is to determine the risk and cofactors for HIV acquisition during pregnancy and postpartum., Design: A prospective cohort study, Methods: : Pregnant women in western Kenya were enrolled if HIV seronegative at that visit or within 3 months. Serial HIV nucleic acid amplification tests (NAATs) were conducted at 1 to 3-month intervals to 9 months postpartum. Genital swabs were collected for detection of chlamydia and gonorrhoea at baseline, and for trichomonas, bacterial vaginosis and yeast at baseline and follow-up., Results: Among 1304 pregnant women, median age was 22 years, 78% were married for a median of 4 years, 66% reported knowing partner HIV status and 8% reported using condoms. Study retention was 98%. During 1235 person-years of follow-up, HIV incidence was 2.31/100 person-years [95% confidence interval (95% CI) 0.71-4.10]. Incident HIV was associated with syphilis (hazard ratio 9.18, 95% CI 2.15-39.3), chlamydia (hazard ratio 4.49, 95% CI 1.34-15.0), bacterial vaginosis (hazard ratio 2.91, 95% CI 1.25-6.76), yeast (hazard ratio 3.46, 95% CI 1.46-8.19), sexually transmitted infection (STI) history (hazard ratio 3.48, 95% CI 1.31-9.27), lifetime number of sex partners (hazard ratio 1.19, 95% CI 1.03-1.37), partner age discordance (hazard ratio 1.07 per year, 95% CI 1.02-1.13) and shorter marriage (hazard ratio 1.19 per year, 95% CI 1.03-1.38). No women with incident HIV reported an HIV-infected partner. In multivariate analyses, chlamydia, older partners and yeast infection remained significant; however, power was limited., Conclusion: Pregnant and lactating women may not perceive HIV risk and rarely used condoms. Prevention and treatment of genital infections and risk stratification to identify women for pre-exposure prophylaxis (PrEP) could decrease HIV acquisition in pregnant/lactating women.

Innate natural killer (NK) cells are diverse at the single-cell level because of variegated expressions of activating and inhibitory receptors, yet the developmental roots and functional consequences of this diversity remain unknown. Because NK cells are critical for antiviral and antitumor responses, a better understanding of their diversity could lead to an improved ability to harness them therapeutically. We found that NK diversity is lower at birth than in adults. During an antiviral response to either HIV-1 or West Nile virus, NK diversity increases, resulting in terminal differentiation and cytokine production at the cost of cell division and degranulation. In African women matched for HIV-1 exposure risk, high NK diversity is associated with increased risk of HIV-1 acquisition. Existing diversity may therefore decrease the flexibility of the antiviral response. Collectively, the data reveal that human NK diversity is a previously undefined metric of immune history and function that may be clinically useful in forecasting the outcomes of infection and malignancy., (Copyright © 2015, American Association for the Advancement of Science.)

Cortisol and inflammatory proteins are released into the blood in response to stressors and chronic elevations of blood cortisol and inflammatory proteins may contribute to ongoing disease processes and could be useful biomarkers of disease. How chronic circadian misalignment influences cortisol and inflammatory proteins, however, is largely unknown and this was the focus of the current study. Specifically, we examined the influence of weeks of chronic circadian misalignment on cortisol, stress ratings, and pro- and anti-inflammatory proteins in humans. We also compared the effects of acute total sleep deprivation and chronic circadian misalignment on cortisol levels. Healthy, drug free females and males (N=17) aged 20-41 participated. After 3weeks of maintaining consistent sleep-wake schedules at home, six laboratory baseline days and nights, a 40-h constant routine (CR, total sleep deprivation) to examine circadian rhythms for melatonin and cortisol, participants were scheduled to a 25-day laboratory entrainment protocol that resulted in sleep and circadian disruption for eight of the participants. A second constant routine was conducted to reassess melatonin and cortisol rhythms on days 34-35. Plasma cortisol levels were also measured during sampling windows every week and trapezoidal area under the curve (AUC) was used to estimate 24-h cortisol levels. Inflammatory proteins were assessed at baseline and near the end of the entrainment protocol. Acute total sleep deprivation significantly increased cortisol levels (p<0.0001), whereas chronic circadian misalignment significantly reduced cortisol levels (p<0.05). Participants who exhibited normal circadian phase relationships with the wakefulness-sleep schedule showed little change in cortisol levels. Stress ratings increased during acute sleep deprivation (p<0.0001), whereas stress ratings remained low across weeks of study for both the misaligned and synchronized control group. Circadian misalignment significantly increased plasma tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10) and C-reactive protein (CRP) (p<0.05). Little change was observed for the TNF-α/IL-10 ratio during circadian misalignment, whereas the TNF-α/IL-10 ratio and CRP levels decreased in the synchronized control group across weeks of circadian entrainment. The current findings demonstrate that total sleep deprivation and chronic circadian misalignment modulate cortisol levels and that chronic circadian misalignment increases plasma concentrations of pro- and anti-inflammatory proteins., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Health care-seeking behaviours of HIV-infected mothers in sub-Saharan Africa are poorly characterised and typically focus on individual health conditions rather than overall health. We conducted a qualitative study to understand how HIV-infected mothers, their male partners and their HIV-exposed infants seek medical services. We performed 32 in-depth interviews (17 female, 15 male) and four focus group discussions among HIV-infected post-partum women and their male partners in Nairobi, Kenya. We used a grounded theory approach to explore the paths followed for health-related concerns. Female participants reported that willingness to be tested for HIV influences whether women sought antenatal care and the type of facility they preferred for childbirth. The need for medical care outside regular clinic hours and securing safe transportation at night were also significant barriers to seeking care. Most men sought services from traditional healers and chemists before HIV diagnosis, and at governmental facilities afterwards. Both men and women sent infants to traditional healers for non-medical conditions such as bewitching and massage but rarely for medical conditions. Strategies to reduce HIV-related stigma and fears in antenatal and maternity settings, increase access to care after-hours and improve linkage to HIV care for men early in their infection are needed.

Background: Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection., Methods and Findings: We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0-4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5-2.1) or postpartum women (HR 1.1, 95% CI 0.6-1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2-3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2-4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity., Conclusions: Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to "high risk" cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.

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., Trials Registration: ClinicalTrials.gov NCT00530777.

Herpes simplex virus-2 (HSV-2) suppression with acyclovir or valacyclovir reduces HIV-1 viral RNA levels; one hypothesis is that HSV-2 suppression reduces immune activation. We measured T cell immune activation markers among women participating in a randomized placebo-controlled trial of valacyclovir to reduce HIV-1 RNA levels among pregnant women. Although valacyclovir was associated with lower HIV-1 RNA levels, the distribution of both CD4(+) and CD8(+) CD38(+)HLA-DR(+) T cells was not different among women taking valacyclovir when compared to women taking placebo. Further study is needed to understand the mechanism of HIV-1 RNA reduction following herpes suppression among those coinfected with HIV-1 and HSV-2.

Background: The effect of herpes simplex virus type 2 (HSV-2) suppression on human immunodeficiency virus type 1 (HIV-1) RNA in the context of prevention of mother-to-child transmission (PMTCT) interventions is unknown., Methods: Between April 2008 and August 2010, we conducted a randomized, double-blind trial of twice daily 500 mg valacyclovir or placebo beginning at 34 weeks gestation in 148 HIV-1/HSV-2 coinfected pregnant Kenyan women ineligible for highly active antiretroviral therapy (CD4 > 250 cells/mm(3)). Women received zidovudine and single dose nevirapine for PMTCT and were followed until 12 months postpartum., Results: Mean baseline plasma HIV-1 RNA was 3.88 log(10) copies/mL. Mean plasma HIV-1 was lower during pregnancy (-.56 log(10) copies/mL; 95% confidence interval [CI], -.77 to -.34) and after 6 weeks postpartum (-.51 log(10) copies/mL; 95% CI, -.73 to -.30) in the valacyclovir arm than the placebo arm. Valacyclovir reduced breast milk HIV-1 RNA detection at 6 and 14 weeks postpartum compared with placebo (30% lower, P = .04; 46% lower, P = .01, respectively), but not after 14 weeks. Cervical HIV-1 RNA detection was similar between arms (P = .91)., Conclusions: Valacyclovir significantly decreased early breast milk and plasma HIV-1 RNA among women receiving PMTCT., Clinical Trials Registration: NCT00530777.

Objective: Herpes simplex virus type 2 (HSV-2) suppression has been shown to reduce HIV-1 disease progression in non-pregnant women and men, but effects on pregnant and postpartum women have not been described., Methods: We analyzed data from a cohort of Kenyan women participating in a randomized clinical trial of HSV-2 suppression. Pregnant HIV-1-seropositive, HSV-2-seropositive women who were not eligible for antiretroviral therapy (WHO stage 1-2, CD4>250 cells/µl) were randomized to either 500 mg valacyclovir or placebo twice daily from 34 weeks gestation through 12 months postpartum. Women received zidovudine and single-dose nevirapine for prevention of mother-to-child HIV-1 transmission. HIV-1 progression markers, including CD4 count and plasma HIV-1 RNA levels, were measured serially. Multivariate linear regression was used to compare progression markers between study arms., Results: Of 148 women randomized, 136 (92%) completed 12 months of postpartum follow-up. While adjusted mean CD4 count at 12 months (565 cells/µl placebo arm, 638 cells/µl valacyclovir arm) increased from antenatal levels in both arms, the mean CD4 count increase was 73 cells/µl higher in the valacyclovir arm than placebo arm (p = 0.03). Mean increase in CD4 count was 154 cells/µl in the valacyclovir arm, almost double the increase of 78 cells/µl in the placebo arm. At 12 months, adjusted HIV-1 RNA levels in the placebo arm increased by 0.66 log(10) copies/ml from baseline, and increased by only 0.21 log(10) copies/ml in the valacyclovir arm (0.40 log(10) copies/ml difference, p = 0.001)., Conclusion: Women randomized to valacyclovir suppressive therapy during pregnancy and postpartum had greater increases in CD4 counts and smaller increases in plasma HIV-1 RNA levels than women in the placebo arm. Valacyclovir suppression during pregnancy and breastfeeding may improve outcomes and delay antiretroviral therapy for HIV-1/HSV-2 co-infected women.

Background: Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described., Methods: Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3) were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis., Results: One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19)., Conclusions: Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events., Trial Registration: ClinicalTrials.gov NCT00530777.

Background: Co-infection with herpes simplex virus type 2 (HSV-2) has been associated with increased HIV-1 RNA levels and immune activation, two predictors of HIV-1 progression. The impact of HSV-2 on clinical outcomes among HIV-1 infected pregnant women is unclear., Methods: HIV-1 infected pregnant women in Nairobi were enrolled antenatally and HSV-2 serology was obtained. HIV-1 RNA and CD4 count were serially measured for 12-24 months postpartum. Survival analysis using endpoints of death, opportunistic infection (OI), and CD4<200 cells µL, and linear mixed models estimating rate of change of HIV-1 RNA and CD4, were used to determine associations between HSV-2 serostatus and HIV-1 progression., Results: Among 296 women, 254 (86%) were HSV-2-seropositive. Only 30 (10%) women had prior or current genital ulcer disease (GUD); median baseline CD4 count was 422 cells µL. Adjusting for baseline CD4, women with GUD were significantly more likely to have incident OIs (adjusted hazard ratio (aHR) 2.79, 95% CI: 1.33-5.85), and there was a trend for association between HSV-2-seropositivity and incident OIs (aHR 3.83, 95% CI: 0.93-15.83). Rate of change in CD4 count and HIV-1 RNA did not differ by HSV-2 status or GUD, despite a trend toward higher baseline HIV-1 RNA in HSV-2-seropositive women (4.73 log10 copies/ml vs. 4.47 log10 copies/ml, P = 0.07)., Conclusions: HSV-2 was highly prevalent and pregnant HIV-1 infected women with GUD were significantly more likely to have incident OIs than women without GUD, suggesting that clinically evident HSV-2 is a more important predictor of HIV-1 disease progression than asymptomatic HSV-2.

Background: HIV treatment programs in Africa typically approach all enrolling patients uniformly. Growing numbers of patients are antiretroviral experienced. Defining patients on the basis of antiretroviral experience may inform enrollment practices, particularly if medical outcomes differ., Methods: Baseline and follow-up measures (CD4, weight change, and survival) were compared in a retrospective analysis between antiretroviral-naïve (ARV-N) and antiretroviral experience (ARV-E) patients enrolled at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya and followed between January 2004 and August 2006., Results: 1,307 ARV-N and 962 ARV-E patients receiving highly active antiretroviral therapy (HAART) were followed for median of 9 months (interquartile range: 4-16 months). Compared to ARV-N, ARV-E had substantially higher CD4 count (median cells/mm(3), 193 versus 95, P < 0.001) and weight (median kg, 62 versus 57, P < 0.001) at baseline, and lower rates of change in CD4 (-9.2 cells/mm(3)/month; 95% CI, -11.4 -7.0) and weight (-0.24 kg/month; 95% CI, -0.35 - -0.14) over 12 months. Mortality was significantly higher in ARV-N than ARV-E (P = 0.001)., Conclusions: ARV-E patients form a growing group that differs significantly from ARV-N patients and requires a distinct approach from ARV-N clients. Systematic approaches to streamline care of ARV-E patients may allow focused attention on early ARV-N clients whose mortality risks are substantially higher.

Background: Although cutaneous malignancy is well known to occur at a higher rate in organ transplant recipients, limited data exist regarding the presentation of squamous cell carcinoma (SCC) in situ in patients with immunosuppression from any cause., Objective: To characterize the presentation of SCC in situ in immunosuppressed patients compared with patients with normal immune function., Methods: A retrospective comparative university-based study, reviewing charts with histologically confirmed Bowen's disease diagnosed between January 1999 and January 2003., Results: Two hundred ninety-nine patients (193 men, 106 women) with 407 SCC in situ tumors were included. Fifty-seven patients (19%) were immunocompromised, including 43 organ transplant recipients, 7 patients with acute and chronic leukemia, and 6 patients with immune-suppressing infections or autoimmune disease. Immunocompromised patients were significantly younger (mean, 61.7 years) than non-immunocompromised patients, 72.6 years, P < .0001) and were more often male (P = .0115). Immunocompromised patients were significantly more likely to have multiple SCC in situ tumors (33% vs 15%; P = .012). Immunocompromised patients were also more likely to present with tumors on the trunk and extremities (odds ratio [OR], 2.03; P = .0019) and particularly on the neck (OR 3.7; P = .00075) than were non-immunocompromised patients. Overall, 11 patients (3.7%) developed a histologically confirmed recurrence of SCC in situ after apparently adequate surgical treatment. The rate of recurrence was higher in immunocompromised (9%) than in non-immunocompromised patients (3%; P = .039)., Limitations: The mean follow-up duration of 35 months may underestimate the recurrence rate., Conclusions: Immunocompromised patients are at significant risk of SCC in situ, and SCC in situ in this population is likely to occur multiply and behave more aggressively. Close dermatologic surveillance of these patients is warranted.

Background: Cutaneous squamous cell carcinoma (SCC) in situ (Bowen's disease; BD) is a common intraepidermal malignancy. The aim of this study was to characterize the demographics, distribution, treatment, and recurrence risk of BD in a university population., Methods: A retrospective survey of histologically confirmed BD diagnosed between January 1999 and January 2003., Results: A total of 299 patients (193 men, 106 women) with 406 cases of BD were identified. The most common sites were the upper extremities (27%), ears (15%), and cheeks (11%). Men were significantly more likely to have SCC in situ on the scalp, ear, and anterior trunk, while the cheek, nose, and lower legs were significantly more common sites among women (p<.05). An office-based procedural treatment was performed in 92% of cases. Elliptical excision was the most common treatment modality (27%) followed by Mohs micrographic surgery (MMS; 20%) and then shave excision (19%). Histologic recurrence was seen in 15 of 406 cases (4%), one of which recurred as invasive SCC. Cryotherapy was associated with the highest recurrence rate (5-year recurrence of 13.4%), followed by topical 5-fluorouracil (9%) and shave excision (9%). Curettage and fulguration (6.5%), MMS (6.3%), and elliptical excision (5.5%) had lower 5-year recurrence rates., Limitations: Our experience at a single institution in the midwestern United States may not be reflective of a wider population., Conclusion: The most common locations for BD were in areas with high sun exposure. Multiple treatment options are available and recurrence is uncommon. Margin control surgery should be considered for tumors in high-risk areas.

Background: Large randomized, controlled clinical trials of lovastatin and gemfibrozil for heart disease prevention have reported statistically significantly lower melanoma incidences in persons receiving these medications. Results of in vitro animal model and human case-control studies also suggest that statins and fibrates may reduce the risk of melanoma., Methods: We performed a systematic review of trials that randomly assigned participants to receive statins or fibrates versus an alternative therapy for a minimum of 6 months. Trials were identified by searching five electronic databases and the reference lists of eligible publications. Unpublished data were solicited from trial investigators and pharmaceutical companies. A meta-analysis was performed using a fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate pooled treatment effects. All statistical tests were two-sided., Results: We obtained data on incident melanomas from 20 of 36 qualifying randomized controlled trials (12 statin trials and eight fibrate trials), with a total of 70,820 participants. A total of 127 melanomas occurred among the 39,426 participants in the statin trials (59 among the 19,872 statin group participants and 68 among the 19,554 control group participants). A total of 27 melanomas occurred among the 31,394 participants enrolled in the fibrate trials (seven among the 12,324 fibrate group participants and 20 among the 19,070 control group participants). Overall, incidence of melanoma was not statistically significantly associated with the use of either statins (OR = 0.87, 95% CI = 0.61 to 1.23) or fibrates (OR = 0.45, 95% CI = 0.20 to 1.01). In a subgroup analysis by drug, only lovastatin use (in one trial) was statistically significantly associated with lower incidence of melanoma (OR = 0.52, 95% CI = 0.27 to 0.99)., Conclusions: These findings do not validate the possibility that statins or fibrates prevent melanoma.

Objectives: To describe youth access to indoor UV tanning and youth discount pricing incentives in 4 states with different age restrictions: Colorado (no age restrictions), Texas (age 13 years), Illinois (age 14 years), and Wisconsin (age 16 years)., Design: Cross-sectional telephone survey conducted in October 2003 using a standardized script to assess the practices of randomly selected UV tanning operators., Participants: Randomly selected licensed indoor UV tanning facility operators in Colorado, Texas, Illinois, and Wisconsin., Main Outcome Measures: Number of facilities (1) complying with indoor UV tanning minimum age regulations for a 12-year-old potential patron and a 15-year-old potential patron and (2) offering youth discounts., Results: For a 12-year-old potential patron, 62% of facilities in states with minimum age restrictions prohibiting 12-year-olds had an operator report that they would not permit indoor tanning (Texas, 23%; Illinois, 74%; and Wisconsin, 89%) compared with 18% in Colorado, a state without youth access regulations. For a 15-year-old patron, most facilities in Wisconsin, the only state with a minimum age restriction for 15-year-olds, prohibited access (77%). Overall, 15% of operators offered youth discounts: Texas, 23%; Illinois, 14%; Wisconsin, 11%; and Colorado, 11%., Conclusions: Tanning facilities in 4 states offered price incentives directed at youths. State youth access regulations were associated with decreased youth access to indoor tanning. High compliance levels in states with long-standing youth access regulations (Illinois and Wisconsin) demonstrate the potential for successful tanning industry youth access regulation.

Objective: Indoor UV tanning is associated with skin cancer. This study describes consumer health risks information provided by indoor UV tanning facility operators in four states (Colorado, Illinois, Texas, and Wisconsin) with varying operator training, regulations, enforcement and penalties., Methods: Using a cross-sectional survey study design, 100 randomly selected licensed indoor UV tanning facilities from each state were surveyed anonymously by telephone. Facility operators were questioned regarding the provision of information on potential adverse effects of indoor UV exposure., Results: Of 628 licensed indoor UV tanning facilities contacted, 400 facilities were surveyed. Most (87%) advised patrons of the potential risk of sunburn from indoor tanning. Less than half of facility operators in Colorado, Texas and Wisconsin informed patrons about the risk of skin cancer (42, 43 and 48%, respectively) compared with 81% of Illinois operators. Likewise, more operators in Illinois reported the risk of premature aging (79%) compared with other states (41% Colorado, 43% Texas and 51% Wisconsin)., Conclusions: Tanning facility operators frequently misinformed patrons of indoor UV exposure risks. The provision of informed consent by indoor tanning facility operators needs improved adaptation by the tanning industry as a standard for customer service.

The use of Internet references in academic literature is common, and Internet references are frequently inaccessible. The extent of Internet referencing and Internet reference activity in medical or scientific publications was systematically examined in more than 1000 articles published between 2000 and 2003 in the New England Journal of Medicine, The Journal of the American Medical Association, and Science. Internet references accounted for 2.6% of all references (672/25548) and in articles 27 months old, 13% of Internet references were inactive. Publishers, librarians, and readers need to reassess policies, archiving systems, and other resources for addressing Internet reference attrition to prevent further information loss.

A myc-containing recombinant feline leukemia provirus, designated FTT, was molecularly cloned from the cat T-cell lymphoma line F422. Its transforming activity, as well as the nucleotide sequence of the 3' 2.7 kilobases of FTT, including v-myc, was determined. The predicted v-myc protein differs from feline c-myc by three amino acid changes and is truncated by two amino acids at the carboxyl terminus. Comparison with feline leukemia virus (FeLV), feline c-myc, and other FeLV proviruses indicates that recombination junctions involved in the generation of FeLV-onc viruses occur at preferred locations within the virus. They usually follow or occur within the sequence ACCCC at 5' junctions and may result from homologous recombination between sequences of marked purine-pyrimidine strand bias, especially at 3' junctions. Some recombination sites also resemble recombinase recognition sequences utilized in immunoglobulin and T-cell receptor variable-region joining. Transfection of primary rat embryo fibroblasts and subsequent in vivo analysis revealed that morphologic and tumorigenic transformation require cotransfection of FTT with human EJ-ras DNA; neither gene alone is sufficient. FTT v-myc is expressed in these transformed rat cells as a 3.0-kilobase subgenomic RNA; however, in contrast to the depressed level of c-myc expression in v-myc-involved feline tumors, steady-state levels of rat c-myc RNA and protein are apparently unaltered.