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Persistent hypertension is common after preeclampsia and is causally tied to later cardiovascular risks. This study examined whether being HIV-infected and on antiretroviral therapy (ART) is associated with persistent postpartum hypertension among women diagnosed with preeclampsia. We conducted a six-month prospective cohort study at Kanyama and Women and Newborn hospitals from January 01, 2022, to June 30, 2023, among 190 women diagnosed with preeclampsia (59 HIV-positive, 131 HIV-negative). Sociodemographic and clinical characteristics were collected at delivery, six weeks, three months and six months after giving birth. Persistent hypertension was diagnosed if a participant presented with elevated blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg and/or taking medication for hypertension at the study visit. We used a generalized estimating equation to describe the relationship between treated HIV and persistent hypertension six months following delivery. We retained 136 participants (71.6%) to six months postpartum, at a median age of 30 years. Overall, persistent hypertension at six weeks, three months, and six months postpartum was common (37.4%, 17.1% and 16.9%, respectively). Six-week postpartum prevalence was higher in the HIV group than HIV-negative group (54.6% vs 28.8%, p<0.001), with no measurable difference at three months (24.3% vs 13.2%, p = 0.145) or six months (18.2% vs 16.3%, p = 0.787). Multivariable analysis demonstrates higher odds (adjusted odds ratio [aOR] = 1.68, 95% CI: 1.09-2.60) of persistent hypertension among the HIV+treatment group than HIV-negative counterparts after accounting for age, body mass index and time since delivery. We demonstrate an elevated risk of persistent hypertension among postpartum women with comorbid preeclampsia and treated HIV. Peripartum patients in HIV-endemic settings may benefit from timely detection of hypertension and treatment interventions to improve health outcomes.

When measured continuously, adherence to HIV pre-exposure prophylaxis (PrEP) is consistently low in studies of pregnant and postpartum women. We investigated how PrEP adherence aligned with HIV exposure risk. We conducted a trial of a PrEP adherence support intervention in Lilongwe, Malawi. Pregnant women who met eligibility criteria for PrEP had visits at three and six months following enrollment. At each visit, HIV exposure risk was categorized as low or moderate/high (i.e., higher) risk based on an algorithm. PrEP adherence was measured via tenofovir concentrations, with functional adherence defined at levels consistent with ≥4 doses/week. HIV exposure risk and PrEP adherence were classified as either aligned (i.e., higher HIV risk/PrEP adherence, low HIV risk/PrEP non-adherence) or not aligned (i.e., higher HIV risk/PrEP non-adherence, low HIV risk/PrEP adherence). Probability differences (PD) were used to estimate the effect of the PrEP adherence intervention on aligned PrEP adherence. 164 women were included in the analysis. HIV exposure risk was higher for 81 participants (49%) at three months and 89 (54%) at six months. PrEP adherence was low at three months (34%) and at six months (29%). Aligned PrEP adherence was observed in 89 (54%) participants at three months and 83 (51%) at six months. 62% at higher HIV exposure risk were not aligned at month three, which increased to 68% at month six. The probability of aligned PrEP adherence was greater among those randomized to the intervention than those receiving standard of care at three months (PD:15.7%; 95%CI:0.8%, 30.6%). This was also evident in analyses that considered women with high HIV risk but low adherence. Alignment of PrEP adherence with HIV exposure risk was dynamic. PrEP adherence should be considered in the context of evolving HIV exposure risk during pregnancy and postpartum, with greater emphasis on periods of elevated HIV risk exposure.

Worldwide, an estimated five million children under the age of five die each year; 47% of these deaths occur during the neonatal period, and the vast majority in low- and middle-income countries. Events during labor are the cause of one quarter of neonatal deaths globally. Basic resuscitation with positive pressure ventilation reduces these deaths but is challenging to execute. To characterize barriers to implementation of basic neonatal resuscitation, we conducted a qualitative study using focus group discussions with midwives at three health facilities in Kinshasa, Democratic Republic of the Congo. We analyzed qualitative data using an inductive content approach in order to identify emergent themes and trends. Twenty-four midwives participated with a median age of 49 and over 80% with more than 10 years of clinical experience. We categorized challenges to implementing basic neonatal resuscitation into three themes with subthemes: 1) limited resources (subthemes: human resource limitations, inadequate and unprepared equipment, insufficient monitoring during labor); 2) inadequate simulated and clinical experience (subthemes: poor systems to support maintenance of skills, infrequent opportunity to resuscitate); 3) emotional burden of resuscitation (subthemes: decision-making under time pressure, tendency to stick to the routine, acute stress during resuscitation, moral distress after unsuccessful outcome). Our findings suggest that while simulation training is key, learning from clinical events may be a critical companion to address these barriers. We call for a new focus on developing and evaluating strategies that support providers in learning from every newborn resuscitation.

Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one's children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women's intrinsic motivation. The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men's role in couples' joint decision-making and women's maternal love as motivators for adherence.

To eliminate mother-to-child transmission of HIV (EMTCT), scalable strategies to enhance antiretroviral adherence for both antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) are needed as part of integrated HIV and maternal-child health services. We developed Tonse Pamodzi (“all of us together”), an adaptable intervention integrating biomedical and behavioral components to support HIV treatment and prevention. We describe our intervention development process, which comprised formative qualitative research, a review of the literature, and technical input from stakeholders representing the community, health systems, and policymakers. The resulting intervention, described herein, integrates patient-centered counseling and engagement of a patient-selected adherence supporter for pregnant and breastfeeding women initiating ART or PrEP. Patients receiving the intervention engage in Integrated Next Step Counseling (iNSC) sessions delivered by trained counselors to build and maintain adherence skills. Each patient also has the option of selecting an adherence supporter (partner, family member, or friend) who may participate in iNSC sessions and provide adherence support outside of these sessions. This flexible intervention is adaptable not only to ART or PrEP use, but also to the needs and preferences of each woman and the clinical context. If shown to be acceptable and feasible, the Tonse Pamodzi intervention may be an important tool in continuing efforts for EMTCT.

There has been tremendous progress in reducing vertical transmission of HIV in the past two decades due to the broad availability of antiretroviral therapy (ART) globally. Despite this progress, new paediatric infections are still occurring. In a pilot study, we evaluated a combination adherence support package, which included an adapted motivational interviewing-informed counselling approach (Integrated Next Step Counselling, iNSC) and an optional adherence supporter, for pregnant and breastfeeding women living with HIV. Participants were recruited from the antenatal clinic in Lilongwe, Malawi. Eligible participants were randomly allocated 1:1 to receive either the combination adherence package (intervention) or standard care (control) at the health facility. Our clinical outcome, measured at three- and six-month follow-up, was a composite endpoint of study retention with HIV viral suppression (HIV RNA <40 copies per mL). We screened 106 women living with HIV between March and July 2020. Of these, 100 women enrolled and were randomly assigned to intervention (n=51) or control (n=49). The majority of participants (94 of 100; 94%) were newly diagnosed with HIV. Retention in care was 92% at three months and 84% at six months. Three-quarters of women retained in care were virally suppressed at the three- and six-month study visits. At three months, our composite outcome (retention & viral suppression) was achieved by 70.6% (36/51) and 69.4% (34/49) of women in the intervention and control groups, respectively. At six months, this composite outcome was achieved by 68.6% (35/51) of the intervention group and 61.2% (30/49) of the control group (probability difference: 7.4%, 95% CI: -11.3%, 26.1%). These encouraging pilot findings suggest that this combination adherence package could be used to support ART adherence among pregnant and breastfeeding women living with HIV. We demonstrate feasibility of using a combined measure of adherence and viral suppression as an outcome measure. ClinicalTrials.gov (NCT04330989).

High HIV incidence rates have been observed among pregnant and breastfeeding women in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) can effectively reduce HIV acquisition in women during these periods; however, understanding of its acceptability and feasibility in antenatal and postpartum populations remains limited. To address this gap, we conducted in-depth interviews with 90 study participants in Malawi and Zambia: 39 HIV-negative pregnant/breastfeeding women, 14 male partners, 19 healthcare workers, and 18 policymakers. Inductive and deductive approaches were used to identify themes related to PrEP. As a public health intervention, PrEP was not well-known among patients and healthcare workers; however, when it was described to participants, most expressed positive views. Concerns about safety and adherence were raised, highlighting two critical areas for community outreach. The feasibility of introducing PrEP into antenatal services was also a concern, especially if introduced within already strained health systems. Support for PrEP varied among policymakers in Malawi and Zambia, reflecting the ongoing policy discussions in their respective countries. Implementing PrEP during the pregnancy and breastfeeding periods will require addressing barriers at the individual, facility, and policy levels. Multi- level approaches should be considered in the design of new PrEP programs for antenatal and postpartum populations.

To eliminate vertical transmission of HIV, global institutions recommend using a risk-guided approach for HIV prevention services in antenatal and postnatal settings. Identifying predictors of maternal HIV acquisition can inform the development of risk-guided approaches, but individual studies of predictors can have limited power and generalizability. We conducted a systematic review and narrative synthesis to identify common predictors of maternal HIV acquisition in sub-Saharan Africa (SSA). We searched four databases for full-text articles that estimated associations between at least one predictor and risk of HIV acquisition among pregnant and/or lactating women (PLW) in SSA. We restricted our synthesis to predictors assessed in at least four study populations. For these predictors, we summarized how each predictor was defined and used vote counting and descriptive statistics to characterize overall trends. We identified 26 eligible publications that summarized results from 24 unique studies. Studies were implemented in 12 countries between 1988 and 2021 and enrolled a total of 164,480 PLW at risk of acquiring HIV. Of the 66 predictors evaluated, 16 met our inclusion criteria. Estimated associations tended to be imprecise and variability in how predictors were measured precluded meta-analyses. We observed trends towards a higher risk of maternal HIV acquisition among young women and women who reported early coital debut, multiple partnerships, sexually transmitted infections, being unaware of partner HIV status, or having a partner living with HIV. In most studies, PLW in stable, monogamous relationships experienced a lower risk of acquiring HIV than those who were single, separated, or in a polygynous marriage. HIV risk perception, condom use, and vaginal drying were also commonly associated with HIV acquisition risk. In our systematic review and narrative synthesis, we identified several easily measured characteristics that were associated with HIV acquisition among PLW in multiple study populations across SSA. Such findings can support the development and refinement of risk-guided approaches for HIV prevention in the region.

Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm (<37 weeks gestation) and/or low birthweight (<2500 g) infants to matched individuals who did not. We measured serum progesterone and prolactin at 24-34 weeks gestation. We used conditional logistic regression to describe relationships between hormone levels, birth outcomes, and antiretroviral regimens. 299 women and their newborns were included (146 cases, 153 controls). When compared to women receiving zidovudine alone, those on ART had higher odds of progesterone levels under the 10th percentile (adjusted odds ratio [AOR]:2.34, 95%CI:1.41-3.89) and 25th percentile (AOR:2.07, 95%CI:1.46-2.94). However, higher levels of progesterone-rather than lower levels-were associated with our composite case outcome at the 10th percentile (AOR:1.88, 95%CI:0.77-4.59) and 25th percentile (AOR:1.96, 95%CI:1.06-3.61). Associations were not observed between prolactin, antiretroviral regimen, and birth outcomes. We observed lower progesterone levels among women allocated to ART regimens; however, higher progesterone levels were associated with preterm birth and/or low birthweight. While features of the study design may have contributed to these findings, they nevertheless highlight the potentially complex mechanisms underpinning adverse birth outcomes and HIV.

Although patient attrition is recognized as a threat to the long-term success of antiretroviral therapy programs worldwide, there is no universal definition for classifying patients as lost to follow-up (LTFU). We analyzed data from health facilities across Africa, Asia, and Latin America to empirically determine a standard LTFU definition. At a set \"status classification\" date, patients were categorized as either \"active\" or \"LTFU\" according to different intervals from time of last clinic encounter. For each threshold, we looked forward 365 d to assess the performance and accuracy of this initial classification. The best-performing definition for LTFU had the lowest proportion of patients misclassified as active or LTFU. Observational data from 111 health facilities-representing 180,718 patients from 19 countries-were included in this study. In the primary analysis, for which data from all facilities were pooled, an interval of 180 d (95% confidence interval [CI]: 173-181 d) since last patient encounter resulted in the fewest misclassifications (7.7%, 95% CI: 7.6%-7.8%). A secondary analysis that gave equal weight to cohorts and to regions generated a similar result (175 d); however, an alternate approach that used inverse weighting for cohorts based on variance and equal weighting for regions produced a slightly lower summary measure (150 d). When examined at the facility level, the best-performing definition varied from 58 to 383 d (mean=150 d), but when a standard definition of 180 d was applied to each facility, only slight increases in misclassification (mean=1.2%, 95% CI: 1.0%-1.5%) were observed. Using this definition, the proportion of patients classified as LTFU by facility ranged from 3.1% to 45.1% (mean=19.9%, 95% CI: 19.1%-21.7%). Based on this evaluation, we recommend the adoption of ≥180 d since the last clinic visit as a standard LTFU definition. Such standardization is an important step to understanding the reasons that underlie patient attrition and establishing more reliable and comparable program evaluation worldwide. Please see later in the article for the Editors' Summary.