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

BACKGROUND:Young 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 FINDINGS:The 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. CONCLUSIONS:In 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

HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants.

BackgroundHIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.MethodsWe conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants.ResultsSARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.ConclusionsThese data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19

Detailed methods for stool viral RNA extraction, RT-PCR, and sequencing.

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SARS-CoV-2 serology and stool viral RNA results over calendar time.

Results of SARS-CoV-2 serology and quantitative real-time PCR testing of stool samples from Linda Kizazi participants that first tested seropositive and had ≥1 available stool sample collected between May 1-December 31, 2020. Anonymized ID numbers on y-axis for mothers (M) and infants (B). Grey circles indicate date of last seronegative serology test and orange circles indicate date of first seropositive sample. White triangles represent SARS-CoV-2 RNA-negative and red triangles represent RNA-positive stool samples. Calendar time is on the x-axis.</p

SARS-CoV-2 antibody levels over time in mother-infant Pairs.

OD ratios show SARS-CoV-2 antibody levels over time in pairs where both mother and infant were first SARS-CoV-2 positive at the same visit and had ≥1 sample available after initial antibody detection. Increased levels of antibody denoted by darker purple shading as shown in key. Positive antibody levels denoted by filled circle, equivocal levels by X, and levels below the limit of detection by empty circles. Mother-infant pairs in which the mother was living with HIV are shown on top with bold red IDs; HIV-uninfected and -unexposed pairs are shown below with black IDs. (TIF)</p

Detection of SARS-CoV-2 antibody among mothers and infants over time.

(A) SARS-CoV-2 antibody levels over time relative to the first seropositive time point (0 months). Individual patterns in infants (top) and mothers (bottom) are shown in grey. Grouped by maternal HIV status, running means are shown for HIV-uninfected women or HIV-unexposed infants in black and women living with HIV or HIV-exposed infants in red. Limit of detection denoted by dashed vertical line. (B) and (C) are Kaplan-Meier hazard functions for participants’ estimated time to loss of detectable antibodies stratified by maternal HIV status and infant HIV exposure, respectively. HEU = HIV-exposed uninfected, HUU = HIV-unexposed uninfected. The risk period for loss of detectable antibody begins at the participant’s first positive serology test and ends either at the time of loss of detectable antibodies (estimated as the midpoint between the last positive test and first negative test after a positive test) or at the time of the most recent positive test.</p

SARS-CoV-2 genomes sequenced from Kenyan stool samples.

Complete SARS-CoV-2 genomes were sequenced from six RNA-positive stool samples. (A) Phylogenetic analyses of 500 randomly selected SARS-CoV-2 global sequences, the Wuhan1 reference, and the two Kenyan stool-derived genomes (indicated in red) are shown. Clade labels are shown. (B) Next-generation sequencing data statistics of the six Kenyan stool samples. (TIF)</p

Incidence of SARS-CoV-2 infection in postpartum Kenyan women and their infants from May 1, 2020 to February 1, 2022.

Incidence of SARS-CoV-2 infection in postpartum Kenyan women and their infants from May 1, 2020 to February 1, 2022.</p