Antibodies from chlamydia-infected individuals facilitate phagocytosis via Fc receptors.

Non-neutralizing functions of antibodies, including phagocytosis, may play a role in Chlamydia trachomatis (CT) infection, but these functions have not been studied and assays are lacking. We utilized a flow-cytometry-based assay to determine whether serum samples from a well-characterized cohort of CT-infected and naïve control individuals enhanced phagocytosis via Fc-receptor-expressing THP-1 cells, and whether this activity correlated with antibody titers. Fc-receptor-mediated phagocytosis was detected only in CT+ donors. Phagocytosis generally did not correlate well with antibody titer. In addition, we found that complement from both CT+ and negative individuals enhanced phagocytosis of CT into primary neutrophils. These results suggest that anti-CT antibodies can have functions that are not reflected by titer. This method could be used to quantitively measure Fc-receptor-mediated function of anti-CT antibodies or complement activity and could reveal new immune correlates of protection.

Low prevalence of bacterial vaginosis in Kenyan adolescent girls and rapid incidence after first sex.

BACKGROUND: Bacterial vaginosis is a risk factor for sexually transmitted infections, including HIV. Adult African women have a high prevalence of bacterial vaginosis, but it is not known when first bacterial vaginosis occurs. OBJECTIVE: This study aimed to describe bacterial vaginosis in younger African women, before and after first sex, and to determine the incidence of bacterial vaginosis and significant correlates of bacterial vaginosis incidence and recurrence. STUDY DESIGN: In a prospective observational cohort study enrolling adolescents with limited sexual experience, young women aged 16 to 21 years were recruited in Thika, Kenya. Eligible participants were HIV and herpes simplex virus 2 seronegative and reported 0 or 1 lifetime sexual partner. The Nugent score was determined at quarterly visits from vaginal Gram stains. The trends in bacterial vaginosis were described over time; hazard ratios were calculated using Cox regression, and relative risk of bacterial vaginosis was estimated using generalized estimating equations and Poisson regression. RESULTS: A total of 400 participants with a median age of 18.6 years (interquartile range, 16-21) were enrolled. Of note, 322 participants (80.5%) reported no history of sex, whereas 78 participants (19.5%) reported sex with 1 partner. At enrollment, bacterial vaginosis (Nugent score of ≥7) was uncommon (21/375 [5.6%]). Overall, 144 participants had bacterial vaginosis at least once, for an incidence rate of 16.5 cases per 100 person-years. Before first sex, bacterial vaginosis was present at 2.8% of visits, compared with 13.7% of visits after first sex. An adjusted model of bacterial vaginosis incidence observed that first sex was associated with more than a 2-fold increased bacterial vaginosis risk (adjusted hazard ratio, 2.44; 95% confidence interval, 1.25-4.76; P=.009). Chlamydia diagnosis (adjusted hazard ratio, 1.73; 95% confidence interval, 1.1-2.8; P=.02), and herpes simplex virus 2 seropositivity (adjusted hazard ratio, 2.88; 95% confidence interval, 1.17-7.09; P=.021) were both associated with incident bacterial vaginosis. A multivariate generalized estimating equation model, including all episodes of bacterial vaginosis, demonstrated risk factors, including first sex, sexually transmitted infections, urban residence, recent sex, and no income; the most important risk factor was first sex (adjusted relative risk, 1.92; 95% confidence interval, 1.12-3.31; P=.018). The probability of bacterial vaginosis increased with each subsequent episode; mean Nugent scores increased after each bacterial vaginosis episode. CONCLUSION: Using detailed longitudinal observation, this study found that Kenyan adolescents have almost no bacterial vaginosis before first sex and that initiation of sexual activity was the strongest risk factor for both prevalent bacterial vaginosis and incident bacterial vaginosis.

"I was just concerned about getting pregnant": Attitudes toward pregnancy and contraceptive use among adolescent girls and young women in Thika, Kenya.

BACKGROUND: Adolescent girls and young women (AGYW) have a high incidence of unplanned pregnancies, especially in low-resource settings. AGYW assess the overlapping risks of pregnancy, contraception, and STIs as they navigate relationships. Few studies have examined how AGYW consider the comparative risks of their decisions around sexual and reproductive health in this context or how risk perception influences contraceptive use. METHODS: Twenty in-depth interviews (IDIs) and 5 focus group discussions (FGDs) were conducted with a subset of sexually active AGYW enrolled in the Girls Health Study (GHS), a longitudinal cohort study in Thika, Kenya, assessing HSV-2 incidence in a cohort of AGYW aged 16-20. Interview questions were focused on perspectives and decision-making around sexual and reproductive health. Interviews were conducted in both English and Kiswahili, transcribed, and coded using inductive and deductive approaches to identify emerging themes. RESULTS: Misconceptions about long-acting reversible contraceptives (LARCs), injectables, and daily oral contraceptive pills strongly disincentivized their use among AGYW. Participants described pregnancy as undesirable, and AGYW reported prioritizing contraceptive methods that were effective and reliable in pregnancy prevention, even if not effective in preventing STI/HIV infection. Participants reported that AGYW relied heavily on emergency contraceptive (EC) pills for pregnancy prevention. CONCLUSIONS: Though the goal of avoiding unintended pregnancy was common, this did not suffice to motivate the uptake of long-term contraceptives among AGYWs. Given the convenience, cost-effectiveness, and lower perceived risk of side effects, EC pills were more likely to be accepted as a form of contraception. Understanding the reasons for AGYW's acceptance of certain contraceptive methods over others can help future interventions better target communication and counseling about contraception and influence key drivers of AGYW behavior and decision-making around sexual and reproductive health.

Antiretroviral Regimen and Pregnancy Outcomes of Women Living with HIV in a US Cohort.

Women who are pregnant and living with HIV have traditionally been excluded from clinical trials regarding new pharmacotherapy. Immediate initiation of antiretroviral therapy (ART) is recommended for women who are pregnant and living with HIV. Integrase inhibitors (INSTIs) are first-line recommended agents as they lead to more rapid HIV viral load reduction. We conducted a retrospective study of women who are pregnant and living with HIV who received prenatal care at the University of Washington. Mothers were categorized by ART class: INSTI, protease inhibitors (PI), and non-nucleoside reverse transcriptase inhibitors (NNRTI). Chi-square and t-tests were used for the analysis of baseline characteristics, and generalized estimating equations were used to adjust for HIV viral suppression between groups. There were a total of 234 mother-infant pairs whose pregnancies progressed beyond 20 weeks. The study demonstrated that women on INSTI regimens were more likely to have a shorter time to viral load suppression than women on NNRTI regimens. Additionally, seven congenital anomalies were identified in this cohort, none of which were neural tube defects. There was no perinatal transmission of HIV to any of the infants. This small cohort of women provides high-quality data regarding the safety and efficacy of INSTI use for both mothers and infants in resource-rich settings.

Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data.

BACKGROUND: Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. METHODS: We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. RESULTS: We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1ß, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. CONCLUSIONS: Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

Influence of Intramuscular Depot Medroxyprogesterone Acetate Initiation on Vaginal Microbiota in the Postpartum Period.

BACKGROUND: The vaginal microbiome plays a key role in women's reproductive health. Use of exogenous hormones, such as intramuscular depot medroxyprogesterone acetate (DMPA-IM), may alter the composition of vaginal bacterial community. METHODS: Vaginal swab samples were collected from postpartum Kenyan women initiating DMPA-IM or nonhormonal contraception (non-HC). Bacterial vaginosis was assessed by Nugent score (Nugent-BV) and bacterial community composition was evaluated using broad-range 16S ribosomal RNA gene polymerase chain reaction with high-throughput sequencing. Changes in Nugent score, alpha diversity (Shannon diversity index), and total bacterial load between contraceptive groups from enrollment to 3 months after initiation were estimated using multivariable linear mixed effects regression. RESULTS: Among 54 human immunodeficiency virus-negative women, 33 choosing DMPA-IM and 21 choosing non-HC, Nugent-BV was more common among DMPA-IM users at enrollment. At follow-up, Nugent score had decreased significantly among DMPA-IM users (change, -1.89; 95% confidence interval [CI], -3.53 to -.25; P = .02) while alpha diversity remained stable (0.03; -.24 to .30; P = .83). Conversely, Nugent score remained relatively stable among non-HC users (change, -0.73; 95% CI, -2.18 to .73; P = .33) while alpha diversity decreased (-0.34; -.67 to -.001; P = .05). The total bacterial load decreased slightly in DMPA-IM users and increased slightly among non-HC users, resulting in a significant difference in change between the contraceptive groups (difference, -0.64 log10 gene copies per swab sample; 95% CI, -1.19 to -.08; P = .02). While significant changes in Nugent score and alpha diversity were observed within contraceptive groups, changes between groups were not significantly different. CONCLUSIONS: Postpartum vaginal bacterial diversity did not change in DMPA-IM users despite a reduction in Nugent-BV, but it decreased significantly among women using non-HC. Choice of contraception may influence Lactobacillus recovery in postpartum women.

Low Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Pregnant and Postpartum Patients With Universal Screening in Seattle, Washington.

We found low prevalence of SARS-CoV-2 (2.7% [5/188]) among pregnant and postpartum patients with universal testing. Prevalence among symptomatic patients was similar under initial targeted screening (22.2% [4/18]) and universal approaches (19.1% [8/42]). Among 170 asymptomatic patients, 2 were positive or inconclusive, respectively; repeat testing at 24 hours was negative.

Protection at First Sexual Intercourse Among Adolescent Girls and Young Women in Kenya.

Adolescent girls and young women (AGYW) are at high risk of HIV and other sexually transmitted infections (STIs), including at first sexual intercourse. The literature is scarce on factors influencing use of protective strategies at this critical time. We conducted 20 in-depth interviews and five focus group discussions with purposively sampled AGYW aged 16-20 years who reported first sex while enrolled in a larger cohort study and willing to participate. All AGYW were counseled on HIV prevention and had access to reproductive health information and services. Data collected were transcribed, translated and analyzed thematically. We identified two approaches to first sex. In one approach, the AGYW facilitated protection use, and those AGYW reported intention and preparation to initiate sexual activity and ability to request condom use, as well as their male partner's willingness to use and provide condoms. In another approach, AGYW experienced first sexual intercourse without agency (the feeling of control over actions and their consequences [Moore, 2016]) and described lack of prior intentions and planning, discomfort with discussions about sex and condom use, and desire to experience sexual pleasure as reported by peers. No AGYW mentioned parents/adults as playing any role as facilitators of protection use at first sex, highlighting the need for further research on the missing gap. The AGYW were trusting of verbal reports by male partners describing themselves as having never engaged in sex, HIV negative, and free of STIs. We found that some AGYW were empowered to plan, discuss, and request protection at first sex, and others did not take agency. First sex is a time of vulnerability where innovative strategies are needed to strengthen AGYW's agency and promote condom use and other HIV/STI prevention methods.

Women's Autonomy in Infant Feeding Decision-Making: A Qualitative Study in Nairobi, Kenya.

BACKGROUND: Exclusive breastfeeding (EBF) is the optimal way to feed young infants. Guidelines recommend that women living with HIV on antiretroviral therapy should EBF for 6 months and continue breastfeeding for up to 24 months or longer. Parents may face social or logistical barriers creating challenges to EBF. OBJECTIVES: To explore barriers, facilitators and community norms influencing EBF practices in Kenya. METHODS: This qualitative research was nested within a longitudinal study of intensive maternal counseling to increase EBF among HIV-positive mothers. HIV-negative and HIV-positive mothers were recruited from four public clinics in Nairobi. Women participated in focus group discussions (FGDs) that explored beliefs about and experiences with infant feeding. Conventional content analysis was used to describe and compare barriers and facilitators influencing HIV-positive and HIV-negative women's EBF experiences. RESULTS: We conducted 17 FGDs with 80 HIV-positive and 53 HIV-negative women between 2009 and 2012. Overall, women agreed that breastmilk is good for infants. However, early mixed feeding was a common cultural practice. HIV-positive women perceived that infant feeding methods and durations were their decision. In contrast, HIV-negative women reported less autonomy and more mixed feeding, citing peer pressure and lack of HIV transmission concerns. Autonomy in decision-making was facilitated by receiving EBF counseling and family support, especially from male partners. Low milk production was a barrier to EBF, regardless of HIV status, and perceived to represent poor maternal nutrition. CONCLUSIONS: Despite challenges, counseling empowered women living with HIV to advocate for EBF with spouses and family.

Cross-Sectional Prevalence of SARS-CoV-2 Among Skilled Nursing Facility Employees and Residents Across Facilities in Seattle.

BACKGROUND: Skilled nursing facilities (SNFs) are high-risk settings for SARS-CoV-2 transmission. Infection rates among employees are infrequently described. OBJECTIVE: To describe SARS-CoV-2 rates among SNF employees and residents during a non-outbreak time period, we measured cross-sectional SARS-CoV-2 prevalence across multiple sites in the Seattle area. DESIGN: SARS-CoV-2 testing was performed for SNF employees and residents using quantitative real-time reverse transcription polymerase chain reaction. A subset of employees completed a sociodemographic and symptom questionnaire. PARTICIPANTS: Between March 29 and May 13, 2020, we tested 1583 employees and 1208 residents at 16 SNFs for SARS-CoV-2. MAIN MEASURE: SARS-CoV-2 testing results and symptom report among employees and residents. KEY RESULTS: Eleven of the 16 SNFs had one or more resident or employee test positive. Overall, 46 (2.9%) employees had positive or inconclusive testing for SARS-CoV-2, and among those who completed surveys, most were asymptomatic and involved in direct patient care. The majority of employees tested were female (934, 73%), and most employees were Asian (392, 30%), Black (360, 28%), or white (360, 28%). Among the 1208 residents tested, 110 (9.1%) had positive or inconclusive results. There was no association between the presence of positive residents and positive employees within a SNF (p = 0.62, McNemar's test). CONCLUSIONS: In the largest study of SNFs to date, SARS-CoV-2 infections were detected among both employees and residents. Employees testing positive were often asymptomatic and involved in direct patient care. Surveillance testing is needed for SNF employees and residents during the pandemic response.

Detection of SARS-CoV-2 Among Residents and Staff Members of an Independent and Assisted Living Community for Older Adults - Seattle, Washington, 2020.

In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.

Firearm storage practices in households with children: A survey of community-based firearm safety event participants.

Safe firearm storage is associated with lower risk of unintentional and intentionally self-inflicted firearm injuries among children and adolescents. Ten community-based firearm safety events were conducted across Washington state from 2015 to 2018. We sought to describe characteristics of event participants and assess whether presence and age of children in the household were associated with household firearm locking practices. We assessed demographic characteristics and baseline firearm storage behaviors of participants using a 13-item survey. Multivariable Poisson regression models were used to estimate prevalence ratios (PR) and corresponding confidence intervals (CI) for the association of presence and age of children in households with prevalence of storing a household firearm unlocked. Of 2956 participants, 58.3% were male and 57.9% lived with an individual under 18 years. Among the 89.8% participants living with firearms, 40.1% stored at least one firearm unlocked and 39.1% stored at least one firearm loaded. In adjusted analyses, there was no statistically significant difference in prevalence of storing a household firearm unlocked between those living with no children (reference group) and those living with a child <11 years (PR = 0.91; 95% CI: 0.80,1.04), or a child aged 11-18 years (PR = 0.94; 95% CI: 0.81,1.09). A high proportion of participants stored a firearm unlocked or loaded at home and neither living with young children nor adolescents was associated with safe locking practices. In comparison with firearm safety interventions conducted in clinic settings, a majority of the participants in these community-based interventions were male and owned firearms.

Male Partner Linkage to Clinic-Based Services for Sexually Transmitted Infections and Human Immunodeficiency Virus Services Following Couple Home-Based Education and Testing.

BACKGROUND: Home-based human immunodeficiency virus (HIV) testing and education has increased HIV test uptake and access to health services among men. We studied how a home-based antenatal intervention influenced male partner utilization of clinic-based HIV and sexually transmitted infection (STI) services, linkage to HIV care and medical circumcision. METHODS: We conducted a secondary analysis within a randomized controlled trial of pregnant women attending antenatal care in Kenya. Women and their male partners received either a home-based couple intervention or an invitation letter for clinic-based couple HIV testing. The home-based intervention included education on STI symptoms, STI and HIV treatment and male circumcision for HIV prevention. Male self-reported outcomes were compared using relative risks at 6 months postpartum. RESULTS: Among 525 women, we reached 487 (93%) of their male partners; 247 men in the intervention arm and 240 men in the control arm. Men who received the intervention were more likely to report an STI consultation (n = 47 vs. 16; relative risk, 1.59; 95% confidence interval, 1.33-1.89). Among 23 men with newly diagnosed HIV, linkage to HIV care was reported by 4 of 15 in the intervention (3 men had missing linkage data) and 3 of 5 men in the control arms (relative risk, 0.66; 95% confidence interval, 0.34-1.29). Although the intervention identified 3 times more men with new HIV infection, the study lacked power to find significant differences in linkage to HIV care. Few eligible men sought medical circumcision (4 of 72 intervention and 2 of 88 control). CONCLUSIONS: Home-based couple education and testing increased STI consultations among male partners of pregnant women, but appeared insufficient to overcome the barriers involved in linkage to HIV care and medical circumcision.

Uptake of Home-Based Syphilis and Human Immunodeficiency Virus Testing Among Male Partners of Pregnant Women in Western Kenya.

BACKGROUND: Few men are tested for syphilis or human immunodeficiency virus (HIV) during their partner's pregnancy, a high-risk period for HIV and syphilis transmission. Offering home-based rapid testing of syphilis to couples during pregnancy can support prevention efforts to reduce transmission of sexually transmitted diseases and adverse pregnancy outcomes. METHODS: We assessed men's uptake of paired (separate tests, single blood draw) point-of-care syphilis and HIV tests within a randomized controlled trial of pregnant women who received clinic or home partner HIV testing. We evaluated acceptance of paired HIV-syphilis testing during pregnancy or at 6 months postpartum, and evaluated whether addition of syphilis testing affected the uptake of HIV testing among men. RESULTS: Of 601 women, we were unable to meet 101 male partners, and 180 tested before syphilis tests were available. Paired syphilis and HIV testing was offered at home to 80 men during pregnancy and to 230 men postpartum. For syphilis, 93% of men agreed to test during pregnancy and 98% agreed postpartum. For paired syphilis and HIV testing, 91% of men tested for both during pregnancy and 96% tested postpartum. Before syphilis test introduction, 96% of men accepted HIV testing, compared with 95% of men who accepted HIV testing when paired testing was offered. CONCLUSIONS: Uptake of syphilis and HIV testing was high among male partners offered couple testing at home. Introducing syphilis testing did not adversely affect HIV testing among men. Point-of-care diagnostics outside facilities can increase testing of male partners who rarely accompany women to antenatal clinics.

Compartmentalized cytomegalovirus replication and transmission in the setting of maternal HIV-1 infection.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)-exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined. METHODS: CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1-infected women to define correlates of maternal CMV replication and infant CMV acquisition. RESULTS: Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (ß = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm(3) (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm(3) to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm(3). CONCLUSIONS: Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

A lifecycle approach to HIV prevention in African women and children.

Effective biomedical and structural HIV prevention approaches are being implemented throughout sub-Saharan Africa. A "lifecycle approach" to HIV prevention recognizes the interconnectedness of the health of women, children and adolescents, and prioritizes interventions that have benefits across these populations. We review new biomedical prevention strategies for women, adolescents and children, structural prevention approaches, and new modalities for eliminating infant HIV infection, and discuss the implications of a lifecycle approach for the success of these methods. Some examples of the lifecycle approach include evaluating education and HIV prevention strategies among adolescent girls not only for their role in reducing risk of HIV infection and early pregnancy, but also to promote healthy adolescents who will have healthier future children. Similarly, early childhood interventions such as exclusive breastfeeding not only prevent HIV, but also contribute to better child and adolescent health outcomes. The most ambitious biomedical infant HIV prevention effort, Option B+, also represents a lifecycle approach by leveraging the prevention benefits of optimal HIV treatment for mothers; maternal survival benefits from Option B+ may have ultimately more health impact on children than the prevention of infant HIV in isolation. The potential for synergistic and additive benefits of lifecycle interventions should be considered when scaling up HIV prevention efforts in sub-Saharan Africa.

Factors associated with reactogenicity to an investigational HIV vaccine regimen in HIV vaccine trials network 702.

BACKGROUND: Reactogenicity informs vaccine safety, and may influence vaccine uptake. We evaluated factors associated with reactogenicity in HVTN 702, a typical HIV vaccine efficacy trial with multiple doses and products. METHODS: HVTN 702, a phase 2b/3 double-blind placebo-controlled trial, randomized 5404 African participants aged 18-35 years without HIV to placebo, or ALVAC-HIV (vCP2438) at months 0, 1 and ALVAC-HIV (vCP2438) + Bivalent Subtype C gp120/MF59 at months 3, 6, 12 and 18. Using multivariate logistic regression, we evaluated associations between reactogenicity with clinical, sociodemographic and laboratory variables. RESULTS: More vaccine than placebo-recipients reported local symptoms (all p < 0.001), arthralgia (p = 0.008), chills (p = 0.012) and myalgia (p < 0.001). Reactogenicity was associated with female sex at birth (ORv = 2.50, ORp = 1.81, both p < 0.001) and geographic region. Amongst vaccine-recipients, each year of age was associated with 3 % increase in reactogenicity (OR = 1.03, p = 0.002). CONCLUSION: Vaccine receipt, female sex at birth, older age, and region may affect reactogenicity.

Valacyclovir suppressive therapy reduces plasma and breast milk HIV-1 RNA levels during pregnancy and postpartum: a randomized trial.

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.