High PrEP uptake and objective longitudinal adherence among HIV-exposed women with personal or partner plans for pregnancy in rural Uganda: A cohort study

Background In Uganda, fertility rates and adult HIV prevalence are high, and many women conceive with partners living with HIV. Pre-exposure prophylaxis (PrEP) reduces HIV acquisition for women and, therefore, infants. We developed the Healthy Families-PrEP intervention to support PrEP use as part of HIV prevention during periconception and pregnancy periods. We conducted a longitudinal cohort study to evaluate oral PrEP use among women participating in the intervention. Methods and findings We enrolled HIV–negative women with plans for pregnancy with a partner living, or thought to be living, with HIV (2017 to 2020) to evaluate PrEP use among women participating in the Healthy Families-PrEP intervention. Quarterly study visits through 9 months included HIV and pregnancy testing and HIV prevention counseling. PrEP was provided in electronic pillboxes, providing the primary adherence measure (“high” adherence when pillbox was opened ≥80% of days). Enrollment questionnaires assessed factors associated with PrEP use. Plasma tenofovir (TFV) and intraerythrocytic TFV-diphosphate (TFV-DP) concentrations were determined quarterly for women who acquired HIV and a randomly selected subset of those who did not; concentrations TFV ≥40 ng/mL and TFV-DP ≥600 fmol/punch were categorized as “high.” Women who became pregnant were initially exited from the cohort by design; from March 2019, women with incident pregnancy remained in the study with quarterly follow-up until pregnancy outcome. Primary outcomes included (1) PrEP uptake (proportion who initiated PrEP); and (2) PrEP adherence (proportion of days with pillbox openings during the first 3 months following PrEP initiation). We used univariable and multivariable-adjusted linear regression to evaluate baseline predictors selected based on our conceptual framework of mean adherence over 3 months. We also assessed mean monthly adherence over 9 months of follow-up and during pregnancy. We enrolled 131 women with mean age 28.7 years (95% CI: 27.8 to 29.5). Ninety-seven (74%) reported a partner with HIV and 79 (60%) reported condomless sex. Most women (N = 118; 90%) initiated PrEP. Mean electronic adherence during the 3 months following initiation was 87% (95% CI: 83%, 90%). No covariates were associated with 3-month pill-taking behavior. Concentrations of plasma TFV and TFV-DP were high among 66% and 47%, 56% and 41%, and 45% and 45% at months 3, 6, and 9, respectively. We observed 53 pregnancies among 131 women (1-year cumulative incidence 53% [95% CI: 43%, 62%]) and 1 HIV-seroconversion in a non-pregnant woman. Mean pillcap adherence for PrEP users with pregnancy follow-up (N = 17) was 98% (95% CI: 97%, 99%). Study design limitations include lack of a control group. Conclusions Women in Uganda with PrEP indications and planning for pregnancy chose to use PrEP. By electronic pillcap, most were able to sustain high adherence to daily oral PrEP prior to and during pregnancy. Differences in adherence measures highlight challenges with adherence assessment; serial measures of TFV-DP in whole blood suggest 41% to 47% of women took sufficient periconception PrEP to prevent HIV. These data suggest that women planning for and with pregnancy should be prioritized for PrEP implementation, particularly in settings with high fertility rates and generalized HIV epidemics. Future iterations of this work should compare the outcomes to current standard of care

Reliability and Validity of Instruments for Assessing Perinatal Depression in African Settings: Systematic Review and Meta-Analysis

Background: A major barrier to improving perinatal mental health in Africa is the lack of locally validated tools for identifying probable cases of perinatal depression or for measuring changes in depression symptom severity. We systematically reviewed the evidence on the reliability and validity of instruments to assess perinatal depression in African settings. Methods and Findings: Of 1,027 records identified through searching 7 electronic databases, we reviewed 126 full-text reports. We included 25 unique studies, which were disseminated in 26 journal articles and 1 doctoral dissertation. These enrolled 12,544 women living in nine different North and sub-Saharan African countries. Only three studies (12%) used instruments developed specifically for use in a given cultural setting. Most studies provided evidence of criterion-related validity (20 [80%]) or reliability (15 [60%]), while fewer studies provided evidence of construct validity, content validity, or internal structure. The Edinburgh postnatal depression scale (EPDS), assessed in 16 studies (64%), was the most frequently used instrument in our sample. Ten studies estimated the internal consistency of the EPDS (median estimated coefficient alpha, 0.84; interquartile range, 0.71-0.87). For the 14 studies that estimated sensitivity and specificity for the EPDS, we constructed 2 x 2 tables for each cut-off score. Using a bivariate random-effects model, we estimated a pooled sensitivity of 0.94 (95% confidence interval [CI], 0.68-0.99) and a pooled specificity of 0.77 (95% CI, 0.59-0.88) at a cut-off score of ≥9, with higher cut-off scores yielding greater specificity at the cost of lower sensitivity. Conclusions: The EPDS can reliably and validly measure perinatal depression symptom severity or screen for probable postnatal depression in African countries, but more validation studies on other instruments are needed. In addition, more qualitative research is needed to adequately characterize local understandings of perinatal depression-like syndromes in different African contexts

A Risk-Factor Guided Approach to Reducing Lactic Acidosis and Hyperlactatemia in Patients on Antiretroviral Therapy

BACKGROUND: Stavudine continues to be used in antiretroviral treatment (ART) regimens in many resource-limited settings. The use of zidovudine instead of stavudine in higher-risk patients to reduce the likelihood of lactic acidosis and hyperlactatemia (LAHL) has not been examined. METHODS: Antiretroviral-naïve, HIV-infected adults initiating ART between 2004 and 2007 were divided into cohorts of those initiated on stavudine- or zidovudine-containing therapy. We evaluated stavudine or zidovudine use, age, sex, body mass index (BMI), baseline CD4 cell count, creatinine, hemoglobin, alanine aminotransferase, and albumin as predictors of time to LAHL with Cox Proportional Hazards (PH) regression models. RESULTS: Among 2062 patients contributing 2747 patient years (PY), the combined incidence of LAHL was 3.2/100 PY in those initiating stavudine- and 0.34/100 PY in those initiating zidovudine-containing ART (RR 9.26, 95% CI: 1.28-66.93). In multivariable Cox PH analysis, stavudine exposure (HR 14.31, 95% CI: 5.79-35.30), female sex (HR 3.41, 95% CI: 1.89-6.19), higher BMI (HR 3.21, 95% CI: 2.16-4.77), higher creatinine (1.63, 95% CI: 1.12-2.36), higher albumin (HR 1.04, 95% CI: 1.01-1.07), and lower CD4 cell count (HR 0.96, 95% CI: 0.92-1.0) at baseline were associated with higher LAHL rates. Among participants who started on stavudine, switching to zidovudine was associated with lower LAHL rates (HR 0.15, 95% CI: 0.06-0.35). Subgroup analysis limited to women with higher BMI≥25 kg/m2 initiated on stavudine also showed that switch to zidovudine was protective when controlling for other risk factors (HR 0.21, 95% CI .07-0.64). CONCLUSIONS: Stavudine exposure, female sex, and higher BMI are strong, independent predictors for developing LAHL. Patients with risk factors for lactic acidosis have less LAHL while on zidovudine- rather than stavudine-containing ART. Switching patients from stavudine to zidovudine is protective. Countries continuing to use stavudine should avoid this drug in women and patients with higher BMI

South Africans with Recent Pregnancy Rarely Know Partner’s HIV Serostatus: Implications for Serodiscordant Couples Interventions

Background: Implementation of safer conception strategies requires knowledge of partner HIV-serostatus. We recruited women and men in a high HIV-prevalence setting for a study to assess periconception risk behavior among individuals reporting HIV-serodiscordant partnerships. We report screening data from that study with the objective of estimating the proportion of individuals who are aware that they are in an HIV-serodiscordant relationship at the time of conception. Methods: We screened women and men attending antenatal and antiretroviral clinics in Durban, South Africa for enrollment in a study of periconception risk behavior among individuals with serodiscordant partners. Screening questionnaires assessed for study eligibility including age 18–45 years (for women) or at least 18 years of age (for men), pregnancy in past year (women) or partner pregnancy in the past 3 years (men), HIV status of partner for recent pregnancy, participant’s HIV status, and infected partner’s HIV status having been known before the referent pregnancy. Results: Among 2620 women screened, 2344 (90%) met age and pregnancy criteria and knew who fathered the referent pregnancy. Among those women, 963 (41%) did not know the pregnancy partner’s HIV serostatus at time of screening. Only 92 (4%) reported knowing of a serodiscordant partnership prior to pregnancy. Among 1166 men screened, 225 (19%) met age and pregnancy criteria. Among those men, 71 (32%) did not know the pregnancy partner’s HIV status and only 30 (13%) reported knowing of a serodiscordant partnership prior to pregnancy. Conclusions: In an HIV-endemic setting, awareness of partner HIV serostatus is rare. Innovative strategies to increase HIV testing and disclosure are required to facilitate HIV prevention interventions for serodiscordant couples

Outcomes After Virologic Failure of First-Line ART in South Africa

Article approval pendingTo determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART)

UV-Optical Pixel Maps of Face-On Spiral Galaxies -- Clues for Dynamics and Star Formation Histories

UV and optical images of the face-on spiral galaxies NGC 6753 and NGC 6782 reveal regions of strong on-going star formation that are associated with structures traced by the old stellar populations. We make NUV--(NUV-I) pixel color-magnitude diagrams (pCMDs) that reveal plumes of pixels with strongly varying NUV surface brightness and nearly constant I surface brightness. The plumes correspond to sharply bounded radial ranges, with (NUV-I) at a given NUV surface brightness being bluer at larger radii. The plumes are parallel to the reddening vector and simple model mixtures of young and old populations, thus neither reddening nor the fraction of the young population can produce the observed separation between the plumes. The images, radial surface-brightness, and color plots indicate that the separate plumes are caused by sharp declines in the surface densities of the old populations at radii corresponding to disk resonances. The maximum surface brightness of the NUV light remains nearly constant with radius, while the maximum I surface brightness declines sharply with radius. An MUV image of NGC 6782 shows emission from the nuclear ring. The distribution of points in an (MUV-NUV) vs. (NUV-I) pixel color-color diagram is broadly consistent with the simple mixture model, but shows a residual trend that the bluest pixels in (MUV-NUV) are the reddest pixels in (NUV-I). This may be due to a combination of red continuum from late-type supergiants and [SIII] emission lines associated with HII regions in active star-forming regions. We have shown that pixel mapping is a powerful tool for studying the distribution and strength of on-going star formation in galaxies. Deep, multi-color imaging can extend this to studies of extinction, and the ages and metallicities of composite stellar populations in nearby galaxies.Comment: LaTeX with AASTeX style file, 29 pages with 12 figures (some color, some multi-part). Accepted for publication in The Astrophysical Journa

“I Always Worry about What Might Happen Ahead”: Implementing Safer Conception Services in the Current Environment of Reproductive Counseling for HIV-Affected Men and Women in Uganda

We explored healthcare provider perspectives and practices regarding safer conception counseling for HIV-affected clients. Methods. We conducted semistructured interviews with 38 providers (medical and clinical officers, nurses, peer counselors, and village health workers) delivering care to HIV-infected clients across 5 healthcare centres in Mbarara District, Uganda. Interview transcripts were analyzed using content analysis. Results. Of 38 providers, 76% were women with median age 34 years (range 24–57). First, we discuss providers\u27 reproductive counseling practices. Emergent themes include that providers (1) assess reproductive goals of HIV-infected female clients frequently, but infrequently for male clients; (2) offer counseling focused on "family planning" and maternal and child health; (3) empathize with the importance of having children for HIV-affected clients; and (4) describe opportunities to counsel HIV-serodiscordant couples. Second, we discuss provider-level challenges that impede safer conception counseling. Emergent themes included the following: (1) providers struggle to translate reproductive rights language into individualized risk reduction given concerns about maternal health and HIV transmission and (2) providers lack safer conception training and support needed to provide counseling. Discussion. Tailored guidelines and training are required for providers to implement safer conception counseling. Such support must respond to provider experiences with adverse HIV-related maternal and child outcomes and a national emphasis on pregnancy prevention

Psychosocial Challenges Facing Women Living with HIV During the Perinatal Period in Rural Uganda

The complexities of navigating pregnancy while living with HIV predispose women to additional stress. Finding ways to minimize psychosocial challenges during the perinatal period may maximize the well-being of mothers living with HIV and their children. The goal of this study was to explore psychosocial challenges experienced by women living with HIV (WLWH) during pregnancy and the postpartum. We conducted individual in-depth interviews with 20 WLWH recruited from an HIV treatment cohort study in Mbarara, Uganda as part of a larger study exploring perinatal depression. We conducted content analyses to identify themes related to challenges of WLWH during pregnancy and the postpartum. Participants had a median age of 33 years [IQR: 28± 35], a median of 3 living children [IQR: 2±5], and 95% had achieved HIV-RNA suppression. Challenges were organized around the following themes: HIV -related stigma from health professionals, HIV status disclosure dilemma, unintended pregnancy and intimate partner violence, HIV and environmental structural barriers and distress and fear related to maternal and child health. Stigma centered on discrimination by health care professionals and personal shame associated with being pregnant as a WLWH. This led to difficulty engaging in HIV care, particularly when coupled with structural barriers, such as lack of transportation to clinic. Participants experienced intimate partner violence and lacked support from their partners and family members. Distress and fear about the health and uncertainty about the future of the unborn baby due to maternal deteriorating physical health was common. The perinatal period is a time of stress for WLWH. Challenges experienced by WLWH may compromise successful engagement in HIV care and may reduce quality of life for women and their children. Strategies aimed at alleviating the challenges of WLWH should involve the larger structural environment including partners, family and community member as well as policy makers, funders and program implementers to work together for the common cause. These consolidated efforts may not only lower the risk of psychological distress but has potential to create long lasting solutions to benefit the wider community

Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health

Lost Opportunities to Reduce Periconception HIV Transmission: Safer Conception Counseling By South African Providers Addresses Perinatal but not Sexual HIV Transmission

Introduction: Safer conception strategies create opportunities for HIV-serodiscordant couples to realize fertility goals and minimize periconception HIV transmission. Patient–provider communication about fertility goals is the first step in safer conception counseling. Methods: We explored provider practices of assessing fertility intentions among HIV-infected men and women, attitudes toward people living with HIV (PLWH) having children, and knowledge and provision of safer conception advice. We conducted in-depth interviews (9 counselors, 15 nurses, 5 doctors) and focus group discussions (6 counselors, 7 professional nurses) in eThekwini District, South Africa. Data were translated, transcribed, and analyzed using content analysis with NVivo10 software. Results: Among 42 participants, median age was 41 (range, 28–60) years, 93% (39) were women, and median years worked in the clinic was 7 (range, 1–27). Some providers assessed women's, not men's, plans for having children at antiretroviral therapy initiation, to avoid fetal exposure to efavirenz. When conducted, reproductive counseling included CD4 cell count and HIV viral load assessment, advising mutual HIV status disclosure, and referral to another provider. Barriers to safer conception counseling included provider assumptions of HIV seroconcordance, low knowledge of safer conception strategies, personal feelings toward PLWH having children, and challenges to tailoring safer sex messages. Conclusions: Providers need information about HIV serodiscordance and safer conception strategies to move beyond discussing only perinatal transmission and maternal health for PLWH who choose to conceive. Safer conception counseling may be more feasible if the message is distilled to delaying conception attempts until the infected partner is on antiretroviral therapy. Designated and motivated nurse providers may be required to provide comprehensive safer conception counseling