A Patient-Centered, Combination Intervention to Support Adherence to HIV Pre-exposure Prophylaxis During Pregnancy and Breastfeeding: A Randomized Pilot Study in Malawi.

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV incidence in pregnant and breastfeeding women, but adherence is essential. METHODS: We conducted a pilot randomized trial to evaluate an intervention package to enhance antenatal and postnatal PrEP use in Lilongwe, Malawi. The intervention was based on patient-centered counseling adapted from previous PrEP studies, with the option of a participant-selected adherence supporter. Participants were locally eligible for PrEP and randomized 1:1 to intervention or standard counseling (ie, control) and followed for 6 months. Participants received the intervention package or standard counseling at enrollment, 1, 3, and 6 months. Adherence was measured through plasma and intracellular tenofovir concentrations and scored using a published algorithm. Our primary outcome was retention in care with concentrations consistent with 4-7 doses/week. RESULTS: From June to November 2020, we enrolled 200 pregnant women with the median gestational age of 26 (interquartile range: 19-33) weeks. Study retention was high at 3 months (89.5%) and 6 months (85.5%). By contrast, across the 2 time points, 32.8% of participants retained in the study had adherence scores consistent with 2-5 doses/week while 10.3% had scores consistent with daily dosing. For the composite primary end point, no substantial differences were observed between the intervention and control groups at 3 months (28.3% vs. 29.0%, probability difference: -0.7%, 95% confidence interval: -13.3%, 11.8%) or at 6 months (22.0% vs. 26.3%, probability difference: -4.3%, 95% confidence interval: -16.1%, 7.6%). CONCLUSIONS: In this randomized trial of PrEP adherence support, retention was high, but less than one-third of participants had pharmacologically confirmed adherence of ≥4 doses/week. Future research should focus on antenatal and postnatal HIV prevention needs and their alignment across the PrEP continuum, including uptake, persistence, and adherence.

Combination HIV prevention during pregnancy and the post-partum period in Malawi and Zambia: a mathematical modelling analysis.

INTRODUCTION: Despite widespread success in reducing vertical HIV transmission, most antenatal care (ANC) programmes in eastern and southern Africa have not emphasized primary prevention of maternal HIV acquisition during pregnancy and lactation/breastfeeding. We hypothesized that combination HIV prevention interventions initiated alongside ANC could substantially reduce maternal HIV incidence. METHODS: We constructed a multi-state model describing male-to-female HIV transmission in steady heterosexual partnerships during pregnancy and lactation/breastfeeding, with initial conditions based on population distribution estimates for Malawi and Zambia in 2020. We modelled individual and joint increases in three HIV prevention strategies at or soon after ANC initiation: (1) HIV testing of male partners, resulting in HIV diagnosis and less condomless sex among those with previously undiagnosed HIV; (2) initiation (or re-initiation) of suppressive antiretroviral therapy (ART) for male partners with diagnosed but unsuppressed HIV; and (3) adherent pre-exposure prophylaxis (PrEP) for HIV-negative female ANC patients with HIV-diagnosed or unknown-status male partners. We estimated the percentage of within-couple, male-to-female HIV transmissions that could be averted during pregnancy and lactation/breastfeeding with these strategies, relative to base-case conditions in which 45% of undiagnosed male partners become newly HIV diagnosed via testing, 75% of male partners with diagnosed but unsuppressed HIV initiate/re-initiate ART and 0% of female ANC patients start PrEP. RESULTS: Increasing uptake of any single strategy by 20 percentage points above base-case levels averted 10%-11% of maternal HIV acquisitions during pregnancy and lactation/breastfeeding in the model. Joint uptake increases of 20 percentage points in two interventions averted an estimated 19%-23% of transmissions, and with a 20-percentage-point increase in uptake of all three interventions, 29% were averted. Strategies achieving 95% male testing, 90% male ART initiation/re-initiation and 40% female PrEP use reduced incident infections by 45%. CONCLUSIONS: Combination HIV prevention strategies provided alongside ANC and sustained through the post-partum period could substantially reduce maternal HIV incidence during pregnancy and lactation/breastfeeding in eastern and southern Africa.

Acceptability of a Combination Adherence Strategy to Support HIV Antiretroviral Therapy and Pre-exposure Prophylaxis Adherence During Pregnancy and Breastfeeding in Malawi.

In two parallel pilot studies, we implemented a combination adherence intervention of patient-centered counselling and adherence supporter training, tailored to support HIV treatment (i.e., antiretroviral therapy) or prevention (i.e., pre-exposure prophylaxis, or PrEP) during pregnancy and breastfeeding. Using a mixed-methods approach, we evaluated the intervention's acceptability. We investigated engagement, satisfaction, and discussion content via survey to all 151 participants assigned to the intervention arm (51 women living with HIV, 100 PrEP-eligible women without HIV). We also conducted serial in-depth interviews with a subgroup (n = 40) at enrollment, three months, and six months. In the quantitative analysis, the vast majority reported high satisfaction with intervention components and expressed desire to receive it in the future, if made available. These findings were supported in the qualitative analysis, with favorable comments about counselor engagement, intervention content and types of support received from adherence supporters. Overall, these results demonstrate high acceptability and provide support for HIV status-neutral interventions for antiretroviral adherence.

Two strategies for partner notification and partner HIV self-testing reveal no evident predictors of male partner HIV testing in antenatal settings: A secondary analysis.

BACKGROUND: To meet global targets for the elimination of mother-to-child HIV transmission, tailored approaches to HIV testing strategies need prioritizing. Herein, we sought to identify individual-level factors associated with male partner HIV testing. METHODS: We conducted a secondary analysis of data from two parallel randomized trials of pregnant women living with HIV and those HIV-negative in Lusaka, Zambia. Across both trials, control groups received partner notification services only, while intervention groups received partner notification services plus HIV self-test kits for their partners. Associations between baseline factors and male partner testing were estimated using a probability difference. The outcome of interest was uptake of male partner HIV testing of any kind within 30 days of randomization. RESULTS: The parent study enrolled 326 participants. Among the 151 women in the control groups, no clear associations were noted between maternal or male partner characteristics and reported uptake of male partner HIV testing. There were positive trends favouring partner testing among women who completed primary school education, had larger households (>2 members), and whose partners were circumcised. Likewise, no clear predictors of male partner testing were identified among the 149 women in the intervention groups. However, negative trends favouring no testing were noted among older, multiparous women from larger households. CONCLUSION: No consistent predictors for male partner HIV testing across two compared strategies were observed. Our findings suggest that differentiated strategies for male partner HIV testing may not be necessary. Instead, consideration should be given to universal approaches when bringing such services to scale.

Strategies to increase couples HIV testing and counselling in sub-Saharan Africa: a systematic review.

INTRODUCTION: Couple HIV testing and counselling (CHTC) is associated with measurable benefits for HIV prevention and treatment. However, the uptake remains limited in much of sub-Saharan Africa, despite an expanded range of strategies designed to promote access. METHODS: Following PRIMSA guidelines, we conducted a systematic review to characterize CHTC uptake strategies. Five databases were searched. Full-text articles were included if they were: conducted in sub-Saharan Africa during the study period (1980-2019), targeted heterosexual couples, reported at least one strategy to promote CHTC and provided a quantifiable measure of CHTC uptake. After the initial and full-text screening, key features of the studies were abstracted and synthesized. RESULTS: Of the 6188 unique records found in our search, 365 underwent full-text review with 29 distinct studies included and synthesized. Most studies recruited couples through antenatal care (n = 11) or community venues (n = 8) and used provider-based HIV testing (n = 25). The primary demand creation strategies included home-based CHTC (n = 7); integration of CHTC into clinical settings (n = 4); distribution of HIV self-testing kits (n = 4); verbal or written invitations (n = 4); community recruiters (n = 3); partner tracing (n = 2); relationship counselling (n = 2); financial incentives (n = 1); group education with CHTC coupons (n = 1); and HIV testing at other community venues (n = 1). CHTC uptake ranged from negligible to nearly universal. DISCUSSION: We thematically categorized a diverse range of strategies with varying levels of intensity and resources used across sub-Saharan Africa to promote CHTC. Offering CHTC within couples' homes was the most common approach, followed by the integration of CHTC into clinical settings. Due to heterogeneity in study characteristics, we were unable to compare the effectiveness across studies, but several trends were observed, including the high prevalence of CHTC promotion strategies in antenatal settings and the promising effects of home-based CHTC, distribution of HIV self-tests and integration of CHTC into routine health services. Since 2019, an updated literature search found that combining partner notification and secondary distribution of HIV self-test kits may be an additionally effective CHTC strategy. CONCLUSIONS: There are many effective, feasible and scalable approaches to promote CHTC that should be considered by national programmes according to local needs, cultural context and available resources.

Addition of HIV self-test kits to partner notification services to increase HIV testing of male partners of pregnant women in Zambia: two parallel randomised trials.

BACKGROUND: Testing men for HIV during their partner's pregnancy can guide couples-based HIV prevention and treatment, but testing rates remain low. We investigated a combination approach, using evidence-based strategies, to increase HIV testing in male partners of HIV-positive and HIV-negative pregnant women. METHODS: We did two parallel, unmasked randomised trials, enrolling pregnant women who had an HIV-positive test result documented in their antenatal record (trial 1) and women who had an HIV-negative test result documented in their antenatal record (trial 2) from an antenatal setting in Lusaka, Zambia. Women in both trials were randomly assigned (1:1) to the intervention or control groups using permuted block randomisation. The control groups received partner notification services only, including an adapted version for women who were HIV-negative; the intervention groups additionally received targeted education on the use of oral HIV self-test kits for their partners, along with up to five oral HIV self-test kits. At the 30 day follow-up we collected information from pregnant women about their primary male partner's HIV testing in the previous 30 days at health-care facilities, at home, or at any other facility. Our primary outcome was reported male partner testing at a health facility within 30 days following randomisation using a complete-case approach. Women also reported male partner HIV testing of any kind (including self-testing at home) that occurred within 30 days. Randomisation groups were compared via probability difference with a corresponding Wald-based 95% CI. The trial is registered at ClinicalTrials.gov (NCT04124536) and all enrolment and follow-up has been completed. FINDINGS: From Oct 28, 2019, to May 26, 2020, 116 women who were HIV-positive (trial 1) and 210 women who were HIV-negative (trial 2) were enrolled and randomly assigned to study groups. Retention at 30 days was 100 (86%) in trial 1 and 200 (95%) in trial 2. Women in the intervention group were less likely to report facility-based male partner HIV testing in trial 1 (3 [6%] of 47 vs 15 [28%] of 53, estimated probability difference -21·9% [95% CI -35·9 to -7·9%]) and trial 2 (3 [3%] of 102 vs 33 [34%] of 98, estimated probability difference -30·7% [95% CI -40·6 to -20·8]). However, reported male partner HIV testing of any kind was higher in the intervention group than in the control group in trial 1 (36 [77%] of 47 vs 19 [36%] of 53, estimated probability difference 40·7% [95% CI 23·0 to 58·4%]) and trial 2 (80 [78%] of 102 vs 54 [55%] of 98, estimated probability difference 23·3% [95% CI 10·7 to 36·0%]) due to increased use of HIV self-testing. Overall, 14 male partners tested HIV-positive. Across the two trials, three cases of intimate partner violence were reported (two in the control groups and one in the intervention groups). INTERPRETATION: Our combination approach increased overall HIV testing in male partners of pregnant women but reduced the proportion of men who sought follow-up facility-based testing. This combination approach might reduce linkages to health care, including for HIV prevention, and should be considered in the design of comprehensive HIV programmes. FUNDING: National Institutes of Health.

Incident HIV among pregnant and breast-feeding women in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVES: A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence. DESIGN: Systematic review and meta-analysis. METHODS: We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression. RESULTS: Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval: 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval: 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval: 0.7--6.5). CONCLUSION: Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women.

Individual, Partner, and Couple Predictors of HIV Infection among Pregnant Women in Malawi: A Case-Control Study.

We aimed to understand drivers of HIV-infection in pregnant women in Malawi. The study was conducted in antenatal and labor and delivery wards. HIV-infected women and their partners (cases) were frequency matched in a 1:2 ratio based on age and screening location to HIV-uninfected women and their partners (controls) in a prevalent case-control study. Characteristics associated with female HIV infection were assessed using logistic regression modeling. At screening, HIV-infected women were more likely to have partners outside Lilongwe than HIV-uninfected women (24% vs. 0%, p < 0.0001). Case females were more likely to have HIV-infected study partners than control females (75% vs. 4%, p < 0.0001). The odds of female HIV-infection were higher if either couple member reported ≥ 2 lifetime marriages (OR 9.0, CI 2.6-30.9) or ≥ 3 lifetime partners (OR 18.0, CI 3.1-103.6) and lower if either reported past couple HIV testing and counseling (OR 0.1, CI 0.04-0.3). Targeting women with migrating partners, promoting couple HIV testing and counseling, and limiting partners could slow HIV transmission.

The Impact of Couple HIV Testing and Counseling on Consistent Condom Use Among Pregnant Women and Their Male Partners: An Observational Study.

BACKGROUND: In sub-Saharan Africa couple HIV testing and counseling (CHTC) has been associated with substantial increases in safe sex, especially when at least one partner is HIV infected. However, this relationship has not been characterized in an Option B+ context. SETTING: The study was conducted at the antenatal clinic at Bwaila District Hospital in Lilongwe, Malawi in 2016 under an Option B+ program. METHODS: Ninety heterosexual couples with an HIV-infected pregnant woman (female-positive couples) and 47 couples with an HIV-uninfected pregnant woman (female-negative couples) were enrolled in an observational study. Each couple member was assessed immediately before and 1 month after CHTC for safe sex (abstinence or consistent condom use in the last month). Generalized estimating equations were used to model change in safe sex before and after CHTC and to compare safe sex between female-positive and female-negative couples. RESULTS: Mean age was 26 years among women and 32 years among men. Before CHTC, safe sex was comparable among female-positive couples (8%) and female-negative couples (2%) [risk ratio (RR): 3.7, 95% confidence interval (CI): 0.5 to 29.8]. One month after CHTC, safe sex was higher among female-positive couples (75%) than among female-negative couples (3%) (RR: 30.0, 95% CI: 4.3 to 207.7). Safe sex increased substantially after CTHC for female-positive couples (RR 9.6, 95% CI: 4.6 to 20.0), but not for female-negative couples (RR: 1.2, 95% CI: 0.1 to 18.7). CONCLUSIONS: Engaging pregnant couples in CHTC can have prevention benefits for couples with an HIV-infected pregnant woman, but additional prevention approaches may be needed for couples with an HIV-uninfected pregnant woman.