Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants.

Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that while the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). However, gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

Longitudinal dynamics of the nasopharyngal microbiome in response to SARS-CoV-2 Omicron variant and HIV infection in Kenyan women and their infants.

The nasopharynx and its microbiota are implicated in respiratory health and disease. The interplay between viral infection and the nasopharyngeal microbiome is an area of increased interest and of clinical relevance. The impact of SARS-CoV-2, the etiological agent of the Coronavirus Disease 2019 (COVID-19) pandemic, on the nasopharyngeal microbiome, particularly among individuals living with HIV, is not fully characterized. Here we describe the nasopharyngeal microbiome before, during and after SARS-CoV-2 infection in a longitudinal cohort of Kenyan women (21 living with HIV and 14 HIV-uninfected) and their infants (18 HIV-exposed, uninfected and 18 HIV-unexposed, uninfected), followed between September 2021 through March 2022. We show using genomic epidemiology that mother and infant dyads were infected with the same strain of the SARS-CoV-2 Omicron variant that spread rapidly across Kenya. Additionally, we used metagenomic sequencing to characterize the nasopharyngeal microbiome of 20 women and infants infected with SARS-CoV-2, 6 infants negative for SARS-CoV-2 but experiencing respiratory symptoms, and 34 timepoint matched SARS-CoV-2 negative mothers and infants. Since individuals were sampled longitudinally before and after SARS-CoV-2 infection, we could characterize the short- and long-term impact of SARS-CoV-2 infection on the nasopharyngeal microbiome. We found that mothers and infants had significantly different microbiome composition and bacterial load (p-values <.0001). However, in both mothers and infants, the nasopharyngeal microbiome did not differ before and after SARS-CoV-2 infection, regardless of HIV-exposure status. Our results indicate that the nasopharyngeal microbiome is resilient to SARS-CoV-2 infection and was not significantly modified by HIV.

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers.

Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. Here, we characterize antibody binding and functionality against Wuhan-Hu-1 (B lineage) strain SARS-CoV-2 in convalescent plasma from 36 postpartum women and 14 of their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. We find significantly higher antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels in infants versus mothers. Plasma antibodies from mothers and infants bind to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants display higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants have significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, Spike pseudovirus neutralization titers between infants and mothers are similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody activities and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers.

Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody repertoires and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.

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

BACKGROUND: HIV 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. METHODS: We 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. RESULTS: SARS-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. CONCLUSIONS: These 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.

Comparison of nucleocapsid and spike antibody ELISAs for determining SARS-CoV-2 seropositivity in Kenyan women and infants.

A multitude of enzyme-linked immunosorbent assays (ELISAs) has been developed to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies since the coronavirus disease 2019 pandemic started in late 2019. Assessing the reliability of these assays in diverse global populations is critical. This study compares the use of the commercially available Platelia Total Ab Assay (Bio-Rad) nucleocapsid ELISA to the widely used Mount Sinai spike IgG ELISA in a Kenyan population seroprevalence study. Using longitudinal plasma specimens collected from a mother-infant cohort living in Nairobi, Kenya between May 2019 and December 2020, this study demonstrates that the two assays have a high qualitative agreement (92.7%) and strong correlation of antibody levels (R2 = 0.973) in repeated measures. Within this cohort, seroprevalence detected by either ELISA closely resembled previously published seroprevalence estimates for Kenya during the sampling period and no significant difference in the incidence of SARS-CoV-2 antibody detection by either assay was observed. Assay comparability was not affected by HIV exposure status. These data support the use of the Platelia SARS-CoV-2 Total Ab ELISA as a suitable high-throughput method for seroprevalence studies in Kenya.

Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers.

Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, which is the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers; however, we observed a very modest association between pre-existing HCoV-229E antibody levels and a lack of SARS-CoV-2 seroconversion in the infants. After seroconversion to SARS-CoV-2, antibody binding titers to the endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not the endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in the mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in the infants, suggesting the increase seen in the mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both the mothers and infants, both of whom were unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we found evidence of increased eHCoV antibody levels following SARS-CoV-2 seroconversion in the mothers but not the infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.

Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers.

Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.

Pediatric HIV Pre-test Informational Video is Associated with Higher Knowledge Scores Compared to Counselor-Delivered Information.

Video-based pre-test information is used in high resource settings to increase HIV testing coverage but remains untested in resource-limited settings. We conducted formative and evaluative focus group discussions with healthcare workers (HCWs) and caregivers of children in Kenya to develop and refine a pediatric HIV pre-test informational video. We then assessed HIV knowledge among caregivers sequentially enrolled in one of three pre-test information groups: (1) individual HCW-led (N = 50), (2) individual video-based (N = 50), and (3) group video-based (N = 50) sessions. A brief video incorporating information on national pediatric testing, modes of HIV transmission, and dramatized testimonials of caregivers who tested children was produced in three languages. Compared to individual HCW-led sessions (mean: 7.2/9; standard deviation [SD]: 1.3), both the group video-based (mean: 7.7; SD: 0.9) and individual video-based (mean: 7.6; SD: 0.9) sessions had higher mean knowledge scores. Video-based pre-test information could enhance existing pediatric HIV testing services.

Dynamic Changes in Breast Milk Microbiome in the Early Postpartum Period of Kenyan Women Living with HIV Are Influenced by Antibiotics but Not Antiretrovirals.

Shared bacteria between maternal breast milk and infant stool, infers that transfer of maternal breast milk microbiota through breastfeeding seeds the establishment of the infant gut microbiome. Whether combination antiretroviral therapy (cART) impacts the breast milk microbiota in women living with HIV is unknown. Since current standard of care for people living with HIV includes cART, it has been difficult to evaluate the impact of cART on the microbiome. Here, we performed a next-generation sequencing retrospective study from pre-ART era clinical trials in Nairobi, Kenya (between 2003-2006 before cART was standard of care) that tested the effects of ART regimens to prevent mother-to-child HIV transmission. Kenyan women living with HIV were randomized to receive either no ART during breastfeeding (n = 24) or cART (zidovudine, nevirapine, lamivudine; n = 25) postpartum. Using linear mixed-effects models, we found that alpha diversity and beta diversity of the breast milk bacterial microbiome changed significantly over time during the first 4 weeks postpartum (alpha diversity P < 0.0007; beta diversity P = 0.005). There was no statistically significant difference in diversity, richness, and composition of the bacterial microbiome between cART-exposed and cART-unexposed women. In contrast, antibiotic use influenced the change of beta diversity of the bacterial microbiome over time. Our results indicate that while early postpartum time predicts breast milk microbiome composition, cART does not substantially alter the breast milk microbiota in women living with HIV. Hence, cART has minimal impact on the breast milk microbiome compared to antibiotics use. IMPORTANCE Breastfeeding has important benefits for long-term infant health, particularly in establishing and shaping the infant gut microbiome. However, the impact of combination antiretroviral therapy exposure and antibiotics on the breast milk microbiome in women living with HIV is not known. Here, in a longitudinal retrospective study of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that antibiotic use significantly influenced breast milk microbiome beta diversity, but antiretrovirals exposure did not substantially alter the microbiome. Given the protective role of breastfeeding in maternal-infant health, these findings fill an important knowledge gap of the impact of combination antiretroviral therapy on the microbiome of women living with HIV.

Cytomegalovirus Viremia and Clinical Outcomes in Kenyan Children Diagnosed With Human Immunodeficiency Virus (HIV) in Hospital.

BACKGROUND: Cytomegalovirus (CMV) viremia is common in human immunodeficiency virus (HIV) infection and is associated with worse long-term outcomes. To date, no studies have assessed CMV viremia in children diagnosed with HIV in hospital. METHODS: We studied CMV viremia and clinical outcomes in 163 Kenyan children aged 2 months to 12 years, diagnosed with HIV in hospital. CMV DNA levels in plasma were measured using quantitative polymerase chain reaction (PCR). Regression models were used to assess associations between CMV viremia ≥1000 IU/mL and the risk of continued hospitalization or death at 15 days, duration of hospitalization, and 6-month mortality. RESULTS: At enrollment, 62/114 (54%) children had CMV viremia, and 20 (32%) were ≥1000 IU/mL. Eleven CMV reactivations were observed after admission. The prevalence and level of CMV viremia were highest in children <2 years and lowest in children ≥5 years old. CMV viremia ≥1000 IU/mL was independently associated with age <2 years (P = .03), higher log10 HIV RNA level (P = .01), and height-for-age z score >-2 (P = .02). Adjusting for age and log10 HIV RNA, the relative risk of death or continued hospitalization at 15 days was 1.74 (95% confidence interval [CI] = 1.04, 2.90), and the hazard ratio of 6-month mortality was 1.97 (95% CI = .57, 5.07) for children with CMV DNA ≥1000 IU/mL compared to lower-level or undetectable CMV DNA. Children with CMV DNA ≥1000 IU/mL were hospitalized a median ~5 days longer than children with lower-level or undetectable CMV DNA (P = .002). CONCLUSIONS: In this nested observational study, CMV viremia was common in hospitalized children with HIV, and levels ≥1000 IU/mL were associated with increased risk of mortality and longer hospitalization.

Contraceptive counseling experiences among women attending HIV care and treatment centers: A national survey in Kenya.

OBJECTIVES: To characterize contraceptive counseling experiences among women living with HIV (WLWH) receiving HIV care in Kenya. STUDY DESIGN: Sexually active, WLWH aged 15 to 49 years were purposively sampled from 109 high-volume HIV Care and Treatment Centers in Kenya between June and September 2016. Cross-sectional surveys were administered to enroll women on a tablet using Open Data Kit. Poisson generalized linear regression models adjusted for facility-level clustering were used to examine cofactors for receiving family planning (FP) counseling with a provider. RESULTS: Overall, 4805 WLWH were enrolled, 60% reported they received FP counseling during the last year, 72% of whom reported they were counseled about benefits of birth spacing and limiting. Most women who received FP counseling were married (64%) and discussed FP with their partner (78%). Use of FP in the last month (adjusted Prevalence Ratio [aPR] = 1.74, 95% confidence interval [CI]: 1.41-2.15, p < 0.001), desire for children in >2 years (aPR = 1.18, 95% CI: 1.09-1.28, p < 0.001), and concern about contraceptive side-effects (aPR = 1.13, 95% CI 1.02-1.25, p < 0.05) were significantly higher among WLWH who received FP counseling compared to those that did not. CONCLUSIONS: Over one-third of WLWH did not receiving FP counseling with an HIV care provider during the last year, and counseling was more commonly reported among women who were using FP or desired children in >2 years. IMPLICATIONS: There are missed opportunities for FP counseling in HIV care. FP integration in HIV care could improve FP access and birth spacing or limiting among WLWH.

Breast Milk Virome and Bacterial Microbiome Resilience in Kenyan Women Living with HIV.

Breast milk is nutritionally and immunologically beneficial in early life but is also a potential source of infection. Little is known about breast milk microbiota of women living with HIV (WLHIV), the impact of severe immunosuppression, and the contribution to mortality of HIV-exposed infants. Here, we performed metagenomic sequencing to characterize the bacterial microbiome and DNA virome of breast milk samples at 1 month postpartum from Kenyan WLHIV who were not receiving combination antiretroviral therapy (cART), 23 women with CD4 counts of <250 and 30 women with CD4 of >500; and additionally, 19 WLHIV with infants that lived and 26 WLHIV with infants that died during the first 2 years of life were included. We found that breast milk bacterial microbiomes in this study population were highly diverse but shared a core community composed of the Streptococcaceae, Staphylococcaceae, Moraxellaceae, and Eubacteriaceae families. The breast milk virome was dominated by human cytomegalovirus (CMV) and included the bacteriophage families Myoviridae, Siphoviridae, and Podoviridae Bacterial microbiome and virome profiles and diversity were not significantly altered by HIV immunosuppression, as defined by a CD4 of <250. CMV viral load was not associated with maternal CD4 counts or infant mortality. In conclusion, we show that the core bacterial and viral communities are resilient in breast milk despite immunosuppression in WLHIV.IMPORTANCE Breastfeeding plays an important role in seeding the infant gut microbiome and mammary health. Although most studies focus on the diverse breast milk bacterial communities, little is known about the viral communities harbored in breast milk. We performed the first breast milk virome study of an HIV population. In this study cohort of Kenyan women living with HIV from the pre-antiretroviral therapy era, we found that breast milk harbors a core bacterial microbiome and a virome dominated by human cytomegalovirus. The virome and bacterial microbiome were not substantially altered by immunosuppression or associated with infant mortality. Together, these findings indicate resilience of the microbial community in breast milk compartmentalization. These findings advance out fundamental understanding of the breast milk core microbiome and virome interactions in the context of HIV disease.

Home- and Clinic-Based Pediatric HIV Index Case Testing in Kenya: Uptake, HIV Prevalence, Linkage to Care, and Missed Opportunities.

INTRODUCTION: Gaps in HIV testing of children persist, particularly among older children born before the expansion of the prevention of mother-to-child transmission of HIV programs. METHODS: The Counseling and Testing for Children at Home study evaluated an index-case pediatric HIV testing approach. Caregivers receiving HIV care at 7 health facilities in Kenya (index cases), who had children of unknown HIV status aged 0-12 years, were offered the choice of clinic-based testing (CBT) or home-based testing (HBT). Testing uptake and HIV prevalence were compared between groups choosing HBT and CBT; linkage to care, missed opportunities, and predictors of HIV-positive diagnosis were identified. RESULTS: Among 493 caregivers, 70% completed HIV testing for ≥1 child. Most caregivers who tested children chose CBT (266/347, 77%), with 103 (30%) agreeing to same-day testing of an untested accompanying child. Overall HIV prevalence among 521 tested children was 5.8% (CBT 6.8% vs HBT 2.4%; P = 0.07). Within 1 month of diagnosis, 88% of 30 HIV-positive children had linked to care, and 54% had started antiretroviral treatment. For 851 children eligible for testing, the most common reason for having an unknown HIV status was that the child's mother was not tested for HIV or had tested HIV negative during pregnancy (82%). CONCLUSION: Testing uptake and HIV prevalence were moderate with nonsignificant differences between HBT and CBT. Standardized offer to test children accompanying caregivers is feasible to scale-up with little additional investment. Linkage to care for HIV-positive children was suboptimal. Lack of peripartum maternal testing contributed to gaps in pediatric testing.

"It's Me as a Person, Not Me the Disease": Patient Perceptions of an HIV Care Model Designed to Engage Persons with Complex Needs.

Ending the HIV epidemic will require dedicated efforts to engage the highest need persons living with HIV (PLWH) in treatment. We assessed patient perceptions of a clinic in Seattle, Washington, that is designed for PLWH who do not engage in conventional HIV care. The Max Clinic provides walk-in access to care, incentives for blood draws and achieving viral suppression, and intensive case management. We conducted semistructured individual interviews with 25 patients purposively recruited to obtain diverse viewpoints. Interviews were audio-recorded and transcribed. Analysis used a constant comparative approach to identify major themes related to the components of the program. For many participants, engagement in the Max Clinic was the first time they had success with HIV treatment. Relationships with clinic staff and the ability to receive care on a walk-in basis had the strongest influences on engagement. Participants felt that Max Clinic staff attended to their social circumstances in ways that were distinct from prior care experiences. Walk-in visits removed perceived stigma associated with failure to keep appointments and provided immediate attention to acute concerns. Financial incentives initially motivated participants to attend clinic and take medications, but were less important for supporting ongoing engagement in care. Food incentives motivated patients to seek care and helped them focus on health issues. In summary, patients identified walk-in access to care, monetary and food incentives, and relationships with clinic staff, particularly case managers, as the key elements of an HIV clinic model for high-need PLWH.

Higher contraceptive uptake in HIV treatment centers offering integrated family planning services: A national survey in Kenya.

OBJECTIVES: Integrating family planning (FP) into routine HIV care and treatment are recommended by WHO guidelines to improve FP access among HIV-infected individuals in sub-Saharan Africa. This study sought to assess factors that influence the delivery of integrated FP services and the impact of facility-level integration of FP on contraceptive uptake among women living with HIV (WLWH). STUDY DESIGN: A national cross-sectional study was conducted among WLWH at HIV Care and Treatment centers with >1000 antiretroviral treatment (ART) clients per year. A mobile team visited 108 HIV Care and Treatment centers and administered surveys to key informants regarding facility attributes and WLWH regarding FP at these centers between June and September 2016. We classified facilities offering FP services within the same facility as 'integrated' facilities. RESULTS: 4805 WLWH were enrolled at 108 facilities throughout Kenya. The majority (73%) of facilities offered integrated FP services. They were more likely to be offered in public than private facilities (Prevalence Ratio [PR]: 1.86, 95% Confidence Interval [CI]: 1.11-3.11; p = 0.02] and were more common in the Nyanza region than the Nairobi region (77% vs 35% respectively, p = 0.06). Any contraceptive use (89% vs 80%), use of modern contraception (88% vs 80%), dual method use (40% vs 30%), long-acting reversible contraception (LARC) (28% vs 20%), and non-barrier short-term methods (34% vs 27%) were all significantly higher in facilities with integrated FP services (p < 0.001). CONCLUSIONS: The majority of high volume facilities integrated FP services into HIV care. Integrating FP services may increase modern contraceptive use among WLWH. IMPLICATIONS: Integration of FP services was associated with higher modern contraceptive use, lower unmet need for modern methods and higher use of long-acting, reversible contraception (LARC), and non-barrier short-term methods among women living with HIV. Despite high prevalence of integration of FP services, organizational challenges remain at integrated clinics.

The Utility of SMS to Report Male Partner HIV Self-testing Outcomes Among Women Seeking Reproductive Health Services in Kenya: Cohort Study.

BACKGROUND: Use of SMS for data collection is expanding, but coverage, bias, and logistical constraints are poorly described. OBJECTIVE: The aim of this study is to assess the use of SMS to capture clinical outcomes that occur at home and identify potential biases in reporting compared to in-person ascertainment. METHODS: In the PrEP Implementation in Young Women and Adolescents program, which integrated pre-exposure prophylaxis (PrEP) into antenatal care, postnatal care, and family planning facilities in Kisumu County, Kenya, HIV-negative women 14 years of age or older were offered oral HIV self-tests (HIVSTs) to take home to male partners. Women that brought a phone with a Safaricom SIM to the clinic were offered registration in an automated SMS system (mSurvey) to collect information on HIVST outcomes. Women were asked if they offered the test to their male partners, and asked about the test process and results. HIVST outcomes were collected via SMS (sent 2.5 weeks later), in-person (if women returned for a follow-up scheduled 1 month later), or using both methods (if women initiated PrEP, they also had scheduled follow-up visits). The SMS prompted women to reply at no charge. HIVST outcomes were compared between women with scheduled follow-up visits and those without (follow-up visits were only scheduled for women who initiated PrEP). HIVST outcomes were also compared between women reporting via SMS and in-person. RESULTS: Among 2123 women offered HIVSTs and mSurvey registration, 486 (23.89%) accepted HIVSTs, of whom 359 (73.87%) were eligible for mSurvey. Additionally, 76/170 (44.7%) women with scheduled follow-up visits and 146/189 (77.3%) without scheduled follow-up visits registered in mSurvey. Among the 76 women with scheduled follow-ups, 62 (82%) had HIVST outcomes collected: 19 (31%) in-person, 20 (32%) by SMS, and 23 (37%) using both methods. Among the 146 women without scheduled visits, 87 (59.6%) had HIVST outcomes collected: 3 (3%) in-person, 82 (94%) by SMS, and 2 (2%) using both methods. SMS increased the collection of HIVST outcomes substantially for women with scheduled follow-up visits (1.48-fold), and captured 82 additional reports from women without scheduled follow-up visits. Among 222 women with reported HIVST outcomes, frequencies of offering partners the HIVST (85/95, 89% in-person vs 96/102, 94% SMS; P=.31), partners using the HIVST (83/85, 98% vs 92/96, 96%; P=.50), women using HIVST with partners (82/83, 99% vs 91/92, 99%; P=.94), and seeing partner's HIVST results (82/83, 99% vs 89/92, 97%; P=.56) were similar between women reporting in-person only versus by SMS only. However, frequency of reports of experiencing harm or negative reactions from partners was more commonly reported in the SMS group (17/102, 16.7% vs 2/85, 2%; P=.003). Barriers to the SMS system registration included not having a Safaricom SIM or a functioning phone. CONCLUSIONS: Our results suggest that the use of SMS substantially improves completeness of outcome data, does not bias reporting of nonsensitive information, and may increase reporting of sensitive information. .

Pre-exposure prophylaxis uptake and early continuation among pregnant and post-partum women within maternal and child health clinics in Kenya: results from an implementation programme.

BACKGROUND: Pregnant women in settings with high HIV prevalence are at increased risk of HIV acquisition and subsequent vertical transmission. We implemented and evaluated a novel programme to provide pre-exposure prophylaxis (PrEP) in maternal and child health clinics in Kenya. METHODS: In collaboration with Kisumu County Department of Health, we integrated PrEP delivery within 16 maternal and child health clinics in Kisumu County (Kenya). Women and girls older than 15 years seeking maternal and child health services who tested HIV negative at that visit or within a month and were willing to receive PrEP counselling were interviewed to assess for HIV behavioural risk factors and offered PrEP. Correlates of PrEP initiation and continuation were assessed using Poisson regression in univariate and multivariate analyses. Potential correlates included in our analyses were age, marital status, marriage type, whether pregnant or post partum, gestational age (if pregnant), and HIV risk factors in the previous 6 months. Reasons for the decision to discontinue after having decided to initiate PrEP were evaluated. Women who initiated PrEP were followed up 1 month, 3 months, and 6 months after initiation. FINDINGS: Between Nov 20, 2017, and June 13, 2018, 9376 pregnant and post-partum women were assessed for behavioural risk factors and willingness to initiate PrEP. Overall, 2030 (21·7%) initiated PrEP, and 2027 had the status of their partner captured (153 [79·3%] of 193 women with partners living with HIV, 1178 [37·2%] of 3165 women with partners of unknown HIV status, and 696 [11·6%] of 5997 women with HIV-negative partners). Predictors of PrEP initiation in the multivariate analysis were: being younger than 24 years (adjusted prevalence ratio 1·14, 95% CI 1·02-1·28); having a partner living with HIV (6·96, 5·46-8·89) or of unknown HIV status (3·08, 2·50-3·81); gestational age of less than 26 weeks (1·22, 1·02-1·47); having been diagnosed or treated for a sexually transmitted infection (1·57, 1·20-2·06); having been forced to have sex (1·82, 1·38-2·42); having experienced intimate partner violence during the previous 6 months (1·65, 1·10-2·48); having shared needles while engaging in injection drug use (2·43, 1·69-3·50); and recurrent use of post-exposure prophylaxis (1·96, 1·36-2·82). Overall, 786 (38·7%) of 2030 women who initiated PrEP continued use after the first month, with 104 (68·0%) of 153 women who had a partner living with HIV continuing use. Having a partner living with HIV was the only predictor of PrEP continuation at 1 month in the multivariable model (1·98, 1·54-2·55). Frequent reasons for discontinuation were side effects and low HIV risk perception. No incident HIV infection was reported among women on PrEP. INTERPRETATION: Many women attending maternal and child health clinics had risk factors for HIV and elected to use PrEP, indicating that routinely accessed maternal and child health clinics can be an effective platform for PrEP delivery for young women. As PrEP awareness rises, PrEP provision in routine clinical settings such as maternal and child health facilities might contribute to decreased HIV incidence among young women. FUNDING: US Department of State.

Perinatal outcomes following maternal pre-exposure prophylaxis (PrEP) use during pregnancy: results from a large PrEP implementation program in Kenya.

INTRODUCTION: The World Health Organization, while recommending pre-exposure prophylaxis (PrEP) for HIV-negative pregnant and postpartum women in HIV high-burden settings, advocates for continued safety evaluation of PrEP in this population. METHODS: The PrEP Implementation in Young Women and Adolescents (PrIYA) program delivered PrEP to pregnant and postpartum women integrated within routine maternal and child health clinics (MCH) at 16 sites in Western Kenya. PrEP exposure and perinatal outcome data were collected among women obtaining postnatal services during programme evaluation. PrEP use was self-reported and confirmed with clinical records. Perinatal outcomes including gestational age at birth, birthweight, congenital malformations and infant growth outcomes were abstracted from clinical records for mother-infant pairs attending the six week visit. Associations between infant outcomes and maternal prenatal PrEP use were assessed using univariate and multivariate logistic and linear regression. RESULTS: The PrIYA evaluation identified 1530 postpartum mother-infant pairs with data on prenatal PrEP exposure: 206 with prenatal PrEP use, 1324 without. Median maternal age was 24 years in both groups. PrEP users (any reported PrEP use) were significantly more likely to report HIV risk factors such as: intimate partner violence, sexually transmitted infections and having a partner with positive or unknown HIV status. Most mothers initiated PrEP during the second trimester (n = 116, 57%) and used PrEP for more than one month (n = 110, 58%). The mean birthweight was 3.3 kg and gestational age at birth was 38.5 weeks in both groups. There were no major differences between PrEP exposed and unexposed infants in rates of preterm birth and low birthweight. There were no congenital malformations identified in the PrEP-exposed group and five reported in the PrEP unexposed group. At six weeks postpartum, infants in both groups had similar growth. No differences in infant outcomes were found by duration PrEP exposure, trimester of PrEP initiation, a subset analysis of women 15 to 24 years old or in multivariate analyses. This analysis demonstrates that monitoring of infant outcomes is feasible within large-scale programmatic implementation of PrEP among pregnant and postpartum populations. CONCLUSIONS: Pregnancy outcomes and early infant growth did not differ by PrEP exposure.