HIV-uninfected Women Research Articles

Effect of efavirenz on levonorgestrel concentrations among Malawian levonorgestrel implant users for up to 30 months of concomitant use: a subanalysis of a randomized clinical trial

ObjectivesOur primary objective was to compare geometric mean levonorgestrel concentrations between levonorgestrel implant users who were or were not taking the antiretroviral efavirenz, for up to 30 months after implant initiation. Our secondary objective was to evaluate the pregnancy rate among levonorgestrel implant users on efavirenz. Study designWe performed a subanalysis of 42 Malawian women randomized to initiate the levonorgestrel implant as part of a parent randomized clinical trial. Our subset included 30 HIV-infected women taking efavirenz and 12 HIV-uninfected women not taking efavirenz. They underwent urine pregnancy testing every 3 months and serum levonorgestrel testing at day 3 and months 1, 3, 6, 12, 18, 24, 27 and 30 after implant initiation. Geometric mean levonorgestrel concentrations were calculated for efavirenz users and non-efavirenz users at each time point. ResultsThe geometric mean levonorgestrel concentrations were lower for efavirenz users than non-efavirenz users at every time point; the geometric mean ratio for efavirenz users:non-efavirenz users ranged from 0.60 [90% confidence interval (CI) 0.46–0.79] at 1 month to 0.27 (90% CI 0.12–0.61) at 30 months after implant insertion. No pregnancies occurred over 60 woman-years of concomitant levonorgestrel implant and efavirenz use, although 11 women had levonorgestrel concentrations <180 pg/mL (the previously suggested minimum threshold concentration for efficacy). ConclusionsEfavirenz users had lower levonorgestrel concentrations than non-efavirenz users, and one third of our concomitant efavirenz and levonorgestrel implant users had concentrations <180 pg/mL. Continued evaluation of the contraceptive efficacy of the levonorgestrel implant may be needed for efavirenz users. ImplicationsAmong 42 Malawian women using the levonorgestrel implant for contraception, women who were taking the antiretroviral efavirenz had lower serum levonorgestrel concentrations than women who were not taking efavirenz. However, none of the women who were taking efavirenz became pregnant over 60 women-years of follow-up.

Loss of Preexisting Immunological Memory Among Human Immunodeficiency Virus-Infected Women Despite Immune Reconstitution With Antiretroviral Therapy.

It is unclear whether human immunodeficiency virus (HIV) infection results in permanent loss of T-cell memory or if it affects preexisting antibodies to childhood vaccinations or infections. We conducted a matched cohort study involving 50 pairs of HIV-infected and HIV-uninfected women. Total memory T-cell responses were measured after anti-CD3 or vaccinia virus (VV) stimulation to measure T cells elicited after childhood smallpox vaccination. VV-specific antibodies were measured by means of enzyme-linked immunosorbent assay (ELISA). There was no difference between HIV-infected and HIV-uninfected study participants in terms of CD4+ T-cell responses after anti-CD3 stimulation (P = .19) although HIV-infected participants had significantly higher CD8+ T-cell responses (P = .03). In contrast, there was a significant loss in VV-specific CD4+ T-cell memory among HIV-infected participants (P = .04) whereas antiviral CD8+ T-cell memory remained intact (P > .99). VV-specific antibodies were maintained indefinitely among HIV-uninfected participants (half-life, infinity; 95% confidence interval, 309 years to infinity) but declined rapidly among HIV-infected participants (half-life; 39 years; 24-108 years; P = .001). Despite antiretroviral therapy-associated improvement in CD4+ T-cell counts (nadir, <200/μL; >350/μL after antiretroviral therapy), antigen-specific CD4+ T-cell memory to vaccinations or infections that occurred before HIV infection did not recover after immune reconstitution, and a previously unrealized decline in preexisting antibody responses was observed.

HIV status, age at cervical Cancer screening and cervical cytology outcomes in an opportunistic screening setting in Nigeria: a 10-year Cross sectional data analysis

BackgroundInvasive cervical cancer (ICC) is more prevalent in HIV infected women and occurs at younger median age than in HIV negative women. Organized cervical cancer screening (CCS) is presently lacking in Nigeria, and the age at CCS is not known in this population. We sought to examine the age at CCS, the cytology outcomes and whether outcomes differ by HIV infection status in an opportunistic screening setting.MethodsCross-sectional analysis of data on a sample of women who had received a CCS in an opportunistic screening service in Jos, Nigeria over a 10-year time period (2006–2016). We used logistic regression models to estimate the independent effect of patient-reported HIV and age at CCS and odds ratios for abnormal cytology outcomes adjusting for other covariates. We also assessed the correlation between median age at CCS and severity of abnormal cervical cytology outcomes. Statistical analyses were done on STATA version 14, College Station, Texas, USA.ResultsIn a sample of 14,088, the median age at CCS was 37 years (IQR; 30–45). For HIV infected women vs. uninfected women, CCS occurred at earlier ages (35.0 ± 7.4 vs 38.2 ± 10.2 years, p < 0.001). All women, regardless of HIV status, who completed at least 7 or more years of education were 1.27 to 3.51 times more likely to have CCS before age 35 than women with less education. The predictors of an abnormal cervical cytology outcome at CCS were: age at CCS ≥ 35 (aOR = 3.57; 95% CI: 2.74, 4.64), multiparity ≥5 (aOR = 1.27; 95% CI: 1.03, 1.56), and provider-referral (aOR = 1.34; 95% CI: 1.09, 1.64). Irrespective of reported HIV status, we found a positive correlation between median age at CCS and severity of cytology outcome.DiscussionThe age at CCS in women who have utilized cervical cancer screening in the study population is relatively late compared to the recommended age by most guidelines from developed settings. Late age at CCS correlates positively with severity of abnormal cytology outcome irrespective of HIV status. More educated women are more likely to have CCS at early age and less likely to have underlying abnormal cytology outcomes.

A cost-effectiveness analysis of antenatal influenza vaccination among HIV-infected and HIV-uninfected pregnant women in South Africa

BackgroundPregnant women and infants are at increased risk of severe disease from influenza. Antenatal influenza vaccination is safe and can reduce the risk of illness for women and their infants. We evaluated for South Africa the health effects of antenatal influenza vaccination among pregnant women and their infants aged <6 months old and assessed its cost-effectiveness. MethodsWe constructed a decision tree model to simulate the population of pregnant women and infants aged <6 months in South Africa using TreeAge Pro Suite 2015. The model evaluated the change in societal costs and outcomes associated with a vaccination campaign that prioritized HIV-infected over HIV-uninfected pregnant women compared with no vaccination. We also examined the impacts of a campaign without prioritization. Upper and lower 90% uncertainty intervals (90% UI) were generated using probabilistic sensitivity analysis on 10000 Monte Carlo simulations. The cost-effectiveness threshold was set to the 2015 per capita gross domestic product of South Africa, US$5724. ResultsAntenatal vaccination with prioritization averted 9070 (90% UI: 7407–11217) total cases of influenza among pregnant women and infants, including 411 (90% UI: 305–546) hospitalizations and 30 (90% UI: 22–40) deaths. This corresponds to an averted fraction of 13.5% (90% UI: 9.0–20.5%). Vaccinating without prioritization averted 7801 (90% UI: 6465–9527) cases of influenza, including 335 (90% UI: 254–440) hospitalizations and 24 (90% UI: 18–31) deaths. This corresponds to an averted fraction of 11.6% (90% UI: 7.8–17.4%). Vaccinating the cohort of pregnant women with prioritization had societal cost of $4689 (90% UI: $3128–$7294) per Quality Adjusted Life Year (QALY) gained while vaccinating without prioritization had a cost of $5924 (90% UI: $3992–$9056) per QALY. ConclusionsAntenatal influenza vaccination campaigns in South Africa would reduce the impact of influenza and could be cost-effective.

Hemagglutinin Stalk Antibody Responses Following Trivalent Inactivated Influenza Vaccine Immunization of Pregnant Women and Association With Protection From Influenza Virus Illness.

BackgroundThe conserved, immuno-subdominant influenza virus hemagglutinin (HA) stalk region is a potential universal group-specific influenza virus vaccine epitope. We analyzed antibody responses to H1 hemagglutinin stalk domain (H1/stalk) following trivalent influenza inactivated vaccine (IIV3) immunization in pregnant women, and association with protection against influenza virus illness.MethodsOne hundred forty-five human immunodeficiency virus (HIV)–uninfected pregnant women (68 IIV3 and 77 placebo recipients) and 140 pregnant women with HIV infection (72 IIV3 and 68 placebo recipients) were independently randomized in placebo-controlled efficacy trials of IIV3. Plasma samples were tested for H1/stalk immunoglobulin G (IgG) and hemagglutination inhibition (HAI) antibodies prevaccination and 1 month postvaccination. Women had weekly surveillance for influenza illness, confirmed by polymerase chain reaction.ResultsIncreases in H1/stalk IgG (and HAI) antibody levels were elicited post-IIV3, with responses being higher in HIV-uninfected women than in women living with HIV. Among HIV-uninfected vaccinees, there was no correlation (postvaccination) between H1/stalk and HAI antibody responses, whereas a strong correlation was observed in vaccinees with HIV. The H1/stalk IgG concentration was lower among women developing A/H1N1 illness (85.3 arbitrary units [AU]/mL) than those without A/H1N1 illness (219.6 AU/mL; P = .001). H1/stalk IgG concentration ≥215 AU/mL was associated with 90% lower odds (odds ratio, 0.09; P = .005) of A/H1N1 illness. Also, H1/stalk IgG was significantly lower among women with influenza B illness (93.9 AU/mL) than among their counterparts (215.5 AU/mL) (P = .04); however, no association was observed after adjusting for HAI titers.ConclusionsH1/stalk IgG concentration was associated with lower odds for A/H1N1 influenza virus illness, indicating its potential as an epitope for a universal vaccine against group 1 influenza virus.

Integrating preexposure prophylaxis delivery in routine family planning clinics: A feasibility programmatic evaluation in Kenya.

BackgroundYoung women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including implementation of preexposure prophylaxis (PrEP). The overarching goal of this project was to demonstrate the feasibility of integrating PrEP delivery within routine family planning (FP) clinics to serve as a platform to efficiently reach at-risk adolescent girls and young women (AGYW) for PrEP in HIV high-burden settings.Methods and findingsThe PrEP Implementation in Young Women and Adolescents (PrIYA) program is a real-world implementation program to demonstrate integration of PrEP delivery for at-risk AGYW in FP clinics in Kisumu, Kenya. Between November 2017 and June 2018, women aged 15 to 45 from the general population seeking FP services at 8 public health clinics were universally screened for HIV behavioral risk factors and offered PrEP following national PrEP guidelines. We evaluated PrEP uptake and continuation, and robust Poisson regression methods were used to identify correlates of uptake and early continuation of PrEP, with age included as a one-knot linear spline. Overall, 1,271 HIV-uninfected women accessing routine FP clinics were screened for PrEP; the median age was 25 years (interquartile range [IQR]: 22–29), 627 (49%) were <24 years old, 1,026 (82%) were married, more than one-third (34%) had partners of unknown HIV status, and the vast majority (n = 1,200 [94%]) reported recent condom-less sex. Of 1,271 women screened, 278 (22%) initiated PrEP, and 114 (41%) returned for at least one refill visit after initiation. PrEP uptake was independently associated with reported male-partner HIV status (HIV-positive 94%, unknown 35%, HIV-negative 8%; p < 0.001) and marital status (28% unmarried versus married 21%; p = 0.04), and a higher proportion of women ≥24 years (26%; 191/740) initiated PrEP compared to 16% (87/531) of young women <24 years (p < 0.001). There was a moderate and statistically non-significant unadjusted increase in PrEP uptake among women using oral contraception pills (OCPs) compared to women using injectable or long-acting reversible contraception methods (OCP 28% versus injectable/implants/intrauterine devices [IUDs] 18%; p = 0.06). Among women with at least one post-PrEP initiation follow-up visit (n = 278), no HIV infection was documented during the project period. Overall, continuation of PrEP use at 1, 3, and 6 months post initiation was 41%, 24%, and 15%, respectively. The likelihood for early continuation of PrEP use (i.e., return for at least one PrEP refill within 45 days post initiation) was strongly associated with reported male-partner HIV status (HIV-positive 67%, -negative 39%, unknown 31%; overall effect p = 0.001), and a higher proportion of women ≥24 years old continued PrEP at 1 month compared with young women <24 years old (47% versus 29%; p = 0.002). For women ≥24 years old, the likelihood to continue PrEP use at 1 month post initiation increased by 3% for each additional year of a woman’s age (adjusted prevalence ratio [PR]: 1.03; 95% confidence interval [CI]: 1.01–1.05; p = 0.01). In contrast, for women <24 years old, the likelihood of continuing PrEP for each additional year of a woman’s age was high in magnitude (approximately 6%) but statistically non-significant (adjusted PR: 1.06; 95% CI: 0.97–1.16; p = 0.18). Frequently reported reasons for discontinuing PrEP were low perceived risk of HIV (25%), knowledge that partner was HIV negative (24%), experiencing side effects (20%), and pill burden (17%). Study limitations include lack of qualitative work to provide insights into women’s decision-making on PrEP uptake and continuation, the small number of measured covariates imposed by the program data, and a nonrandomized design limiting definitive ascertainment of the robustness of a PrEP-dedicated nurse-led implementation strategy.ConclusionsIn this real-world PrEP implementation program in Kenya, integration of universal screening and counseling for PrEP in FP clinics was feasible, making this platform a potential “one-stop” location for FP and PrEP. There was a high drop-off in PrEP continuation, but a subset of women continued PrEP use at least through 1 month, possibly indicating further reflection or decision-making on PrEP use. Greater efforts to support PrEP normalization and persistence for African women are needed to help women navigate their decisions about HIV prevention preferences as their reproductive goals and HIV vulnerability evolve.

Seroprevalence of Cytomegalovirus Infection Among HIV-Infected and HIV-Uninfected Pregnant Women Attending Antenatal Clinic in Harare, Zimbabwe.

This study aimed to investigate the seroprevalence of cytomegalovirus (CMV) infection and risk factors associated with CMV acquisition among pregnant women in Zimbabwe. In a cross-sectional study, pregnant women were recruited in late gestation, seeking antenatal care at council clinics in three high-density suburbs in Harare, Zimbabwe. Anti-CMV IgM and IgG antibodies were quantified in serum using an enzyme-linked immunosorbent assay. Antibody avidity tests were used to distinguish active infection from viral reactivation in anti-CMV IgM-positive cases. Five hundred and twenty four women were recruited: 278 HIV infected and 246 HIV uninfected. Current or active CMV infection defined as IgM positive+low avidity was detected in 4.6% (24/524), 95% confidence interval (CI): 3–6.9 in all women, 5.8% (16/278) in the HIV infected and 3.3% (8/246), 95% CI: 1.4–6.3 in the HIV uninfected. IgG seroprevalence was 99.6% (522/524), 95% CI: 98.6–99.9 in all women. Notably, the difference in the prevalence of active CMV infection between the HIV-infected and HIV-uninfected women was not statistically significant (p = 0.173). The study shows a low prevalence of primary or active CMV infection among the pregnant women, but the IgG seroprevalence suggests high previous CMV exposure. Importantly, CMV seroprevalence was not associated with the HIV status of the women, perhaps due to the ubiquitous exposure of the population to CMV.

Low Disclosure of PrEP Nonadherence and HIV-Risk Behaviors Associated With Poor HIV PrEP Adherence in the HPTN 067/ADAPT Study.

We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg. Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant-Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence. Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant-Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(β) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(β) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001]. Given the association with adherence, study staff-participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.

Brief Report: High Rates of Adverse Birth Outcomes in HIV and Syphilis Coinfected Women in Botswana.

Little is known about the combined impact of HIV/syphilis coinfection on birth outcomes. Antenatal HIV and syphilis test results, obstetric history, and infant birth outcomes were collected from obstetric records in maternity wards in Botswana between 2008 and 2011 (5 sites) and 2014 and 2016 (8 sites). We used logistic regression to compare adverse birth outcomes by HIV and syphilis status. Outcomes included stillbirth, preterm delivery, low birth weight, and in-hospital neonatal death. Of 76,466 women, 75,770 (99.1%) had HIV test results, and 20,520 (27.1%) were HIV positive. Syphilis test results were available for 67,290 (88.0%), and 697 (1.0%) had reactive rapid plasma reagin. Among 692 women with syphilis and an HIV test result, 261 (37.7%) were coinfected. HIV-infected women were more likely to be infected with syphilis than HIV-uninfected women [odds ratio (OR) = 1.68; 95% confidence interval (CI): 1.44 to 1.96]. From 2008-2011 to 2014-2016, the proportion of women with syphilis remained constant (1.1% vs. 1.0%, P = 0.41), but HIV/syphilis coinfection declined from 45% to 27% (P < 0.0001). Stillbirth occurred in 5.8% of coinfected women, compared with 1.9% with no HIV/syphilis (OR = 3.09; 95% CI: 1.83 to 5.23); 3.4% with HIV alone (OR = 1.75; 95% CI: 1.03 to 2.97), or 3.7% with syphilis alone (OR = 1.58; 95% CI: 0.77 to 3.25). Low birth weight occurred in 24.1% of coinfected women, compared with 12.1% with no HIV/syphilis (OR 2.31; 95% CI: 1.74 to 3.08; 20% with HIV alone (OR = 1.27; 95% CI: 0.96 to 1.69); or 14.6% with syphilis alone (OR = 1.85; 95% CI: 1.26 to 2.74). Although HIV/syphilis coinfection in pregnancy has declined in the past decade, coinfection was associated with adverse birth outcomes.

Impact of Intermittent Preventive Treatment of Malaria in Pregnancy with Dihydroartemisinin-Piperaquine Versus Sulfadoxine-Pyrimethamine on the Incidence of Malaria in Infancy: A Randomised Controlled Trial

Background: Intermittent preventive treatment of malaria during pregnancy (IPTp) with dihydroartemisinin-piperaquine significantly reduces the burden of malaria during pregnancy compared to the current standard of care, sulfadoxine-pyrimethamine, but its impact on the incidence of malaria during infancy is unknown. Methods: We conducted a double-blind randomised trial to compare the incidence of malaria during infancy among infants born to HIV-uninfected pregnant women who were randomised to monthly IPTp with either dihydroartemisinin-piperaquine or sulfadoxine-pyrimethamine. Infants were followed for all their medical care in a dedicated study clinic including routine assessments conducted every 4 weeks. At any visit, infants with fever and a positive thick blood smear were diagnosed and treated for malaria. The primary outcome was the incidence of malaria during the first 12 months of life. All analyses were done by modified intention to treat. Results: Among 782 women enrolled, 687 were followed through delivery resulting in 678 live births between December 9, 2016 and December 5, 2017; 339 born to mothers randomised to receive sulfadoxine-pyrimethamine and 339 born to mothers randomised to receive dihydroartemisinin-piperaquine. A total of 581 infants (85·7%) were followed to 12 months of age. Overall, the incidence of malaria was lower among infants born to mothers randomised to dihydroartemisinin-piperaquine compared to sulfadoxine-pyrimethamine, but the difference was not statistically significant (1·71 vs 1·98 episodes per person year, incidence rate ratio (IRR) 0·87, 95% CI 0·73-1·03, p=0·11). When stratifying by infant sex and age, IPTp with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria among male infants (IRR 0·75, 95% CI 0·58-0·98, p=0·03) and infants >3-9 months of age (IRR 0·79, 95% CI 0·64-0·98, p=0·03). Interpretation: Compared to IPTp with sulfadoxine-pyrimethamine, IPTp with dihydroartemisinin-piperaquine was associated with a lower incidence of malaria during infancy among male infants and infants >3-9 months of age. Trial Registration: This trial was registered at ClinicalTrials.gov (NCT02793622) Funding Statement: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill and Melinda Gates Foundation. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The study was approved by Makerere University School of Biomedical Sciences Ethics Committee, the Uganda National Council of Science and Technology, and the University of California San Francisco Research Ethics Committee. In addition, retrospective approval for the infancy phase of the study was obtained from the London School of Hygiene and Tropical Medicine Ethics Committee. The parents/guardians of all participants provided written informed consent before enrollment.

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population.

Trivalent influenza vaccination randomized control trial of pregnant women and adverse fetal outcomes

IntroductionThe purpose of this study was to evaluate the association of influenza vaccine during pregnancy and adverse fetal outcomes. Preventing fetal death, low birth weight, small for gestational age birth and preterm birth are important potential effects of antenatal maternal influenza immunization for which there are conflicting data. Materials and methodsA double-blind, randomized, placebo-controlled clinical trial of trivalent inactivated influenza vaccine was conducted in South Africa from March 2011 until after the 2012 influenza season when the infants born had reached the age of 24 weeks. Mothers were administered the vaccine or placebo during pregnancy at a gestation of 20 to 36 weeks. A comparison of rates of fetal death, low birth weight, small for gestational age birth, and preterm birth, between vaccinated and placebo groups was made. Fetal outcome differences between the groups were measured using Student’s t-tests, vaccine efficacy with 95% confidence intervals, and Poisson regression for incidence rates. All analyses except fetal death excluded mothers who were administered vaccine or placebo after 34 weeks gestational age. ResultsThere were 2116 HIV-uninfected pregnant women age 18 to 38 years in the trial; 2005 infants were born to mothers where vaccine or placebo had been administered ≥ 14 days prior to delivery, and there were 6 miscarriages and 23 stillbirths. There was no significant vaccine efficacy (with [95% confidence interval]) on fetal death (−21.2% [−150.8, 41.4]), low birth weight (−11.1% [−42.3, 12.5]), small for gestational age birth (−9.9% [−35.6, 11.0]), or preterm birth (−21.3% [−60.5, 8.3]). Neither was vaccine efficacy demonstrated when the analysis was restricted to infants of mothers who were exposed to an influenza season (1832 outcomes available). ConclusionWe did not find a beneficial effect of trivalent inactivated influenza vaccine during pregnancy on adverse fetal outcomes.

The Zambian Preterm Birth Prevention Study (ZAPPS): Cohort characteristics at enrollment.

Background:Sub-Saharan Africa bears a disproportionate burden of preterm birth and other adverse outcomes. A better understanding of the demographic, clinical, and biologic underpinnings of these adverse outcomes is urgently needed to plan interventions and inform new discovery. Methods:The Zambian Preterm Birth Prevention Study (ZAPPS) is a prospective observational cohort established at the Women and Newborn Hospital (WNH) in Lusaka, Zambia. We recruit pregnant women from district health centers and the WNH and offer ultrasound examination to determine eligibility. Participants receive routine obstetrical care, lab testing, midtrimester cervical length measurement, and serial fetal growth monitoring. At delivery, we assess gestational age, birthweight, vital status, and sex and assign a delivery phenotype. We collect blood, urine, and vaginal swab specimens at scheduled visits and store them in an on-site biorepository.In September 2017, enrollment of the ZAPPS Phase 1-the subject of this report-was completed. Phase 2, which is limited to HIV-uninfected women, reopened in January 2018. Results:Between August 2015 and September 2017, we screened 1784 women, of whom 1450 (81.2%) met inclusion criteria and were enrolled. The median age at enrollment was 27 years (IQR 23-32) and median gestational age was 16 weeks (IQR 13-18). Among women with a previous pregnancy (n=1042), 19% (n=194) reported a prior miscarriage. Among parous women (n=992), 41% (n=411) reported a prior preterm birth and 14% (n=126) reported a prior stillbirth. The HIV seroprevalence was 24%. Discussion:We have established a large cohort of pregnant women and newborns at the WNH to characterize the determinants of adverse birth outcomes in Lusaka, Zambia. Our overarching goal is to elucidate biological mechanisms in an effort to identify new strategies for early detection and prevention of adverse outcomes. We hope that findings from this cohort will help guide future studies, clinical care, and policy.

Protocol for a longitudinal study to evaluate the use of tenofovir-based PrEP for safer conception and pregnancy among women in South Africa

IntroductionWomen who choose to conceive a baby with a partner living with HIV or a partner whose HIV serostatus is unknown in HIV-endemic settings need prevention strategies to mitigate HIV...

Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa.

ObjectivesSexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine.MethodsBetween November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy.ResultsIn 242 women (median age 29 years [IQR = 24–34], median gestation 19 weeks [IQR = 14–24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02–3.67), being unmarried or not cohabiting with the fetus’ father (aOR = 2.19; 95% CI = 1.16–4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08–20.95) were associated with STI diagnosis.ConclusionWe found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

Elevated Depressive Symptoms Are a Stronger Predictor of Executive Dysfunction in HIV-Infected Women Than in Men.

HIV-infected (HIV+) women seem to be more vulnerable to neurocognitive impairment (NCI) than HIV+ men, perhaps in part due to mental health factors. We assessed the association between elevated depressive symptoms and NCI among HIV+ and HIV-uninfected (HIV-) women and men. Women's Interagency HIV Study and Multicenter AIDS Cohort Study. Eight hundred fifty-eight HIV+ (429 women; 429 men) and 562 HIV- (281 women; 281 men) completed the Center for Epidemiologic Studies Depression (16 cutoff) Scale and measures of psychomotor speed/attention, executive, and motor function over multiple visits (or time points). Women's Interagency HIV Study and Multicenter AIDS Cohort Study participants were matched according to HIV status, age, race/ethnicity, and education. Generalized linear mixed models were used to examine interactions between biological sex, HIV serostatus, and depression on impairment (T-scores <40) after covariate adjustment. Despite a higher frequency of depression among men, the association between depression and executive function differed by sex and HIV serostatus. HIV+ women with depression had 5 times the odds of impairment on a measure of executive control and inhibition versus HIV- depressed women and 3 times the odds of impairment on that measure versus HIV+ depressed men. Regardless of group status, depression was associated with greater impairment on processing speed, executive (mental flexibility), and motor function (P's < 0.05). Depression contributes to NCI across a broad range of cognitive domains in HIV+ and HIV- individuals, but HIV+ depressed women show greater vulnerabilities in executive function. Treating depression may help to improve cognition in patients with HIV infection.

Acceptability and outcomes of distributing HIV self-tests for male partner testing in Kenyan maternal and child health and family planning clinics.

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. 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. 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. 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.

Comparison on simultaneous capillary and venous parasite density and genotyping results from children and adults with uncomplicated malaria: a prospective observational study in Uganda

BackgroundBlood smear microscopy remains the gold-standard method to diagnose and quantify malaria parasite density. In addition, parasite genotyping of select loci is the most utilized method for distinguishing recrudescent and new infections and to determine the number of strains per sample. In research settings, blood may be obtained from capillary or venous compartments, and results from these matrices have been used interchangeably. Our aim was to compare quantitative results for parasite density and strain complexity from both compartments.MethodsIn a prospective observational study, children and adults presenting with uncomplicated Plasmodium falciparum malaria, simultaneous capillary and venous blood smears and dried blood spots were collected over 42-days following treatment with artemether-lumefantrine. Blood smears were read by two microscopists, any discrepancies resolved by a third reader. Parasite DNA fingerprinting was conducted using six microsatellites. Bland Altman analysis and paired t-test/McNemar’s test were used to assess the difference in density readings and measurements.ResultsTwo hundred twenty-three participants were included in the analysis (177 children (35 HIV-infected/142 HIV-uninfected), 21 HIV-uninfected pregnant women, and 25 HIV-uninfected non-pregnant adults). Parasite density measurements did not statistically differ between capillary and venous blood smears at the time of presentation, nor over the course of 42-day follow-up. Characterization of merozoite surface protein-2 (MSP-2) genetic polymorphism demonstrated a higher level of strain diversity at the time of presentation in venous samples, as compared with capillary specimens (p = 0.02). There was a high degree of variability in genotype-corrected outcomes when pairs of samples from each compartment were compared using MSP-2 alone, although the variability was reduced with the use of multiple markers.ConclusionsParasite density measurements do not statistically differ between capillary and venous compartments in all studied demographic groups at the time of presentation with malaria, or over the course of follow-up. More strains were detected by MSP-2 genotyping in venous samples than in capillary samples at the time of malaria diagnosis. The use of multiple polymorphic markers reduces the impact of variability in strain detection on genotype-corrected outcomes. This study confirms that both capillary and venous compartments can be used for sampling with confidence in the clinical research setting.Trial registrationThe trial was registered at ClinicalTrials.gov under registration no. NCT01717885.

Long-acting reversible contraception knowledge, attitudes and use among HIV-infected and -uninfected women and their providers

Objective(s)To describe differences in contraceptive knowledge, attitudes and use among HIV-infected and HIV-uninfected women served by an academic medical center in New York City and to describe gaps in knowledge and practice of gynecologic and HIV clinicians providing care at the same clinic sites where patients completed surveys. Study designWe conducted a survey comparing contraceptive knowledge, attitudes, reproductive histories and long-acting reversible contraception (LARC) use in HIV-infected and -uninfected women. We also conducted a survey to elicit clinician demographic characteristics and education, contraceptive practice patterns and their knowledge of current contraceptive guidelines. We surveyed clinicians and patients at five ambulatory sites. ResultsWe screened 90% of patients approached. All 257 women who were eligible completed a survey. These included 107 (42%) HIV-infected women and 150 (58%) HIV-uninfected women. HIV-infected women were older, were more likely to be black/African-American, were less likely to be Latina, were more likely to receive public assistance and had lower educational attainment. HIV-infected women reported lower lifetime LARC use (12% vs. 28%) and higher recent condom use (58% vs. 25%) than HIV-uninfected women. Both groups reported similar attitudes toward intrauterine devices (IUDs) and implants. HIV clinicians were less likely to have had training in or discuss LARC methods with their patients. ConclusionsHIV-infected women were less likely to be current (last 30 days) or ever LARC users, despite having similar attitudes toward IUDs and implants, compared to HIV-uninfected women. HIV providers had lower levels of knowledge of HIV-specific contraceptive guidelines compared with gynecology practitioners. ImplicationsHIV-infected women and their providers share a knowledge gap regarding LARC. Increased interdisciplinary collaboration may help mitigate the resulting disparities in access to highly effective contraception in HIV-infected women. Knowledge of HIV-specific contraceptive guidelines and ability to place contraceptive implants were low among all surveyed providers, suggesting need for additional training.

Breastfeeding Support Offered at Delivery is Associated with Higher Prevalence of Exclusive Breastfeeding at 6 Weeks Postpartum Among HIV Exposed Infants: A Cross-Sectional Analysis.

Objective HIV-exposed uninfected infants are almost twice as likely to die compared to infants born to HIV-uninfected women. HIV-exposed uninfected children whose mothers are on ART and who are breastfed have the lowest risk of dying by 24months of age. Interventions to improve breastfeeding among HIV-infected mothers are needed. We aimed to assess the association between support/counseling provided by healthcare workers following delivery and the rate of exclusive breastfeeding (EBF) at 6-week postpartum. Methods This is a secondary analysis of data collected as part of a trial to evaluate the effect of conditional cash transfers on retention in and uptake of PMTCT services. Between April 2013 and August 2014, newly diagnosed HIV-infected women, ≤ 32weeks pregnant, registering for antenatal care (ANC), in 89 clinics in Kinshasa, Democratic Republic of Congo, were recruited and followed through 6 weeks postpartum. At 6-week, participants were asked if they had given anything other than breastmilk to their infant in the 24h preceding the interview (No = EBF) and whether a nurse or a doctor talked to them about breastfeeding after they gave birth (YES = received breastfeeding support/counseling). Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) measuring the strength of the association between EBF and receiving breastfeeding support/counseling by a healthcare provider following delivery. Results Of 433 women enrolled, 328 attended a 6-week postpartum visit including 320 (97%) with complete information on EBF. Of those 320, 202 (63%) reported giving nothing other than breastmilk to their infant in the previous 24h; 252 (79%) reported that a healthcare provider came to talk to them about breastfeeding following delivery. Mothers who reported receiveing breastfeeding support/counseling from a healthcare provider were more likely to exclusively breastfeed compared to those who did not (69% vs. 38%, OR 3.74; 95% CI 2.14-6.54). Adjustment for baseline sociodemographic characteristics did not change the association substantially, (adjusted OR 3.72; 95% CI 2.06-6.71). Conclusion for Practice Receipt of breastfeeding support/counseling from a healthcare provider after delivery among HIV-infected mothers in care at 6-weeks postpartum in Kinshasa almost quadrupled the odds of EBF.