HIV-uninfected Pregnant Women Research Articles

Vaginal Microbiome and the Risk of Preterm Birth in Women Living With HIV: A Scoping Review.

There are sparse data on the role of thevaginal microbiome (VMB) in pregnancy among pregnant women living with HIV (PWLWH) and its association with spontaneous preterm birth (sPTB). We conducted a scoping review to assess associations between vaginal microbiota and sPTB among PWLWH. Three studies were included, representing a total of 180 PWLWH out of 652 total pregnancies. All studies used modern DNA sequencing methods (16S rRNA amplification, metagenomics, or metatranscriptomics). PWLWH had higher VMB richness and diversity compared to HIV-uninfected pregnant women and higher sPTB rates in two of three studies. A higher proportion of sPTB among PWLWH was observed in those with Lactobacillus-deficient, anaerobe-dominant vaginal microbiota. In two of three studies, higher concentrations of vaginal inflammation markers were associated with increased VMB richness and diversity. HIV status was independently associated with sPTB. It is unclear if increased vaginal microbial diversity among PWLWH or increased vaginal inflammation contributes more to PTB, but HIV does appear to alter the VMB in pregnant individuals and may also affect PTB rates in microbiome-independent pathways. Given the limited number of studies, heterogeneity in sample size, sample collection methods, and inconsistent results it is difficult to causally link HIV, VMB, inflammatory cytokines, and sPTB.

The Impact of Antiretroviral Therapy on Birth Outcomes: A Retrospective Cohort Study

Objective: This study aimed to evaluate the impact of highly active antiretroviral therapy (HAART) on pregnancy outcomes at a major tertiary hospital in Abuja, Nigeria. Design: A cohort study was conducted. Methods: HIV-infected pregnant women who initiated HAART during pregnancy for the prevention of mother-to-child transmission (pMTCT) were recruited, alongside a randomly selected group of HIV-uninfected pregnant women. Results: A total of 489 pregnant women participated, including 237 HIV-infected and 252 HIV-uninfected women. HAART initiation during pregnancy was significantly associated with higher mean birth weights (p = 0.0007). While there were 30 cases of low birth weight in the HIV-infected group compared to 21 in the HIV-uninfected group, HAART was not significantly associated with low birth weight (OR 1.59, p = 0.1182). There were 6 stillbirths in the HIV-infected group and 5 in the uninfected group, with no significant association between HIV status and stillbirth (OR 1.28, p = 0.6836). However, 29 preterm deliveries occurred in the HIV-infected group compared to 8 in the uninfected group, showing a strong association between HIV infection and preterm deliveries despite HAART initiation (OR 4.25, p = 0.0002). Conclusion: HIV-infected women receiving HAART during pregnancy have a significantly reduced risk of low birth weight but face an increased risk of preterm delivery.

T-cell responses to ancestral SARS-CoV-2 and Omicron variant among unvaccinated pregnant and postpartum women living with and without HIV in South Africa

SARS-CoV-2 cell-mediated immunity remains understudied during pregnancy in unvaccinated Black African women living with HIV (WLWH) from low- and middle-income countries. We investigated SARS-CoV-2-specific T-cell responses 1 month following infection in 24 HIV-uninfected women and 15 WLWH at any stage during pregnancy or postpartum. The full-length spike (FLS) glycoprotein and nucleocapsid (N) protein of wild-type (WT) SARS-CoV-2, as well as mutated spike protein regions found in the Omicron variant (B.1.1.529) were targeted by flow cytometry. WT-specific CD4+ and CD8+ T cells elicited similar FLS- and N-specific responses in HIV-uninfected women and WLWH. SARS-CoV-2-specific T-lymphocytes were predominantly TNF-α monofunctional in pregnant and postpartum women living with and without HIV, with fever cells producing either IFN-γ or IL-2. Furthermore, T-cell responses were unaffected by Omicron-specific spike mutations as similar responses between Omicron and the ancestral virus were detected for CD4+ and CD8+ T cells. Our results collectively demonstrate comparable T-cell responses between WLWH on antiretroviral therapy and HIV-uninfected pregnant and postpartum women who were naïve to Covid-19 vaccination. Additionally, we show that T cells from women infected with the ancestral virus, Beta variant (B.1.351), or Delta variant (B.1.617.2) can cross-recognize Omicron, suggesting an overall preservation of T-cell immunity.

Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting

BackgroundDespite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting.MethodsPregnant women ≥ 20 weeks’ gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity.Results Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87–1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy.HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009.In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61–10.7) and 2.46 (1.07–5.34), respectively.None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule.ConclusionLow and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden.Trial registrationwww.clinicaltrials.gov, trial registration number: NCT04087239.

Immunogenicity of tetanus, diphtheria and acellular pertussis vaccination among pregnant women living with and without HIV.

Vaccination during pregnancy with tetanus-diphtheria-acellular pertussis (Tdap) vaccine is recommended to protect the young infants against pertussis. There is a paucity of data on immune responses to Tdap in pregnant women living with HIV (PWLWH), and its impact on the protection of their infants has not been described. In an open label phase IV clinical trial in South Africa, we evaluated the immunogenicity and safety of Tdap in PWLWH compared with HIV-uninfected women. Antigen-specific immunoglobulin G (IgG) to pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae, diphtheria and tetanus were measured by electrochemiluminescence-based multiplex assay. Overall 91 PWLWH and 136 HIV-uninfected pregnant women were enrolled. All PWLWH were on antiretroviral treatment and 94.5% had HIV viral loads <40 copies per millilitre. Antibody levels pre-vaccination were lower among PWLWH compared with HIV-uninfected women for all antigens. At one-month post-vaccination PWLWH compared with HIV-uninfected women had lower fold-increase and antibody concentrations for all epitopes. Also, a lower proportion of PWLWH achieved ≥4-fold increase from pre to post-vaccination for pertussis toxoid and pertactin, or diphtheria IgG levels ≥0.1IU/mL and ≥1IU/mL post-vaccination. Adverse events post-vaccination were similar in PWLWH and HIV-uninfected. Tdap vaccination was safe and immunogenic. PWLHW had, however, attenuated humoral immune responses, which could affect the effectiveness of protecting their infants against pertussis compared with those born to women without HIV. ClinicalTrials.gov identifier: NCT05264662.

Evaluating the use of oral pre-exposure prophylaxis among pregnant and postpartum adolescent girls and young women in Cape Town, South Africa.

Adolescent girls and young women (AGYW) in South Africa are at a higher risk of acquiring HIV. Despite the increasing availability of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention, knowledge on PrEP use during pregnancy and postpartum periods at antenatal care (ANC) facilities remains inadequate. Data from HIV-uninfected pregnant women in Cape Town, South Africa, were used in this study. These women aged 16-24 years were enrolled in the PrEP in pregnancy and postpartum (PrEP-PP) cohort study during their first ANC visit. Using the PrEP cascade framework, the outcomes of the study were PrEP initiation (prescribed tenofovir disoproxil fumarate and emtricitabine at baseline), continuation (returned for prescription), and persistence [quantifiable tenofovir diphosphate (TFV-DP) in dried blood samples]. The two primary exposures of this study were risk perception for HIV and baseline HIV risk score (0-5), which comprised condomless sex, more than one sexual partner, partner living with HIV or with unknown serostatus, laboratory-confirmed sexually transmitted infections (STIs), and hazardous alcohol use before pregnancy (Alcohol Use Disorders Identification Test for Consumption score ≥ 3). Logistic regression was used to examine the association between HIV risk and PrEP, adjusting for a priori confounders. A total of 486 pregnant women were included in the study, of which 16% were "adolescents" (aged 16-18 years) and 84% were "young women" (aged 19-24 years). The adolescents initiated ANC later than the young women [median = 28 weeks (20-34) vs. 23 weeks (16-34), p = 0.04]. Approximately 41% of the AGYW were diagnosed with sexually transmitted infection at baseline. Overall, 83% of the AGYW initiated PrEP use during their first ANC. The percentage of PrEP continuation was 63% at 1 month, 54% at 3 months, and 39% at 6 months. Approximately 27% consistently continued PrEP use through 6 months, while 6% stopped and restarted on PrEP use at 6 months. With a higher risk score of HIV (≥2 vs. ≤1), the AGYW showed higher odds of PrEP continuation [adjusted odds ratio: 1.85 (95% CI: 1.12-3.03)] through 6 months, adjusting for potential confounders. Undergoing the postpartum period (vs. pregnant) and having lower sexual risk factors were found to be the barriers to PrEP continuation. TFV-DP concentration levels were detected among 49% of the AGYW, and 6% of these women had daily adherence to PrEP at 3 months. AGYW were found to have high oral PrEP initiation, but just over one-third of these women continued PrEP use through 6 months. Pregnant AGYW who had a higher risk of acquiring HIV (due to condomless sex, frequent sex, and STIs) were more likely to continue on PrEP use through the postpartum period. Pregnant and postpartum AGYW require counseling and other types of support, such as community delivery and peer support to improve their effective PrEP use through the postpartum period. ClinicalTrials.gov, NCT03826199.

Antenatal gut microbiome profiles and effect on pregnancy outcome in HIV infected and HIV uninfected women in a resource limited setting

BackgroundHuman immunodeficiency virus (HIV) severely damages the epithelial cells of the gut lining leading to an inflamed leaky gut, translocation of microbial products, and dysbiosis resulting in systemic immune activation. Also, microbiota composition and maternal gut function can be altered in pregnancy through changes in the immune system and intestinal physiology. The aim of this study was to investigate the gut microbiota in HIV-infected and HIV-uninfected pregnant women and to compare and identify the association between gut microbial composition and adverse birth outcomes.ResultsA total of 94 pregnant women (35 HIV-infected and 59 HIV-uninfected controls) were recruited in Harare from 4 polyclinics serving populations with relatively poor socioeconomic status. Women were of a median age of 28 years (interquartile range, IQR: 22.3–32.0) and 55% of women were 35 weeks gestational age at enrolment (median 35.0 weeks, IQR: 32.5–37.2). Microbiota profiling in these participants showed that species richness was significantly lower in the HIV-infected pregnant women compared to their HIV-uninfected peers and significant differences in β-diversity using Bray–Curtis dissimilarity were observed. In contrast, there was no significant difference in α-diversity between immune-compromised (CD4+ < 350 cells/µL) and immune-competent HIV-infected women (CD4+ ≥ 350 cells/µL) even after stratification by viral load suppression. HIV infection was significantly associated with a reduced abundance of Clostridium, Turicibacter, Ruminococcus, Parabacteroides, Bacteroides, Bifidobacterium, Treponema, Oscillospira, and Faecalibacterium and a higher abundance of Actinomyces, and Succinivibrio. Low infant birth weight (< 2500 g) was significantly associated with high abundances of the phylum Spirochaetes, the families Spirochaeteceae, Veillonellaceae, and the genus Treponema.ConclusionThe results reported here show that the species richness and taxonomy composition of the gut microbiota is altered in HIV-infected pregnant women, possibly reflecting intestinal dysbiosis. Some of these taxa were also associated with low infant birth weight.

Point-of-Care Sexually Transmitted Infection Testing Improves HIV Preexposure Prophylaxis Initiation in Pregnant Women in Antenatal Care in Cape Town, South Africa, 2019 to 2021.

A study of HIV-uninfected pregnant women in South Africa found that women offered point-of-care sexually transmitted infection testing had higher odds of initiating HIV preexposure prophylaxis than women offered laboratory-based testing. Background Preexposure prophylaxis (PrEP) programs present a platform for diagnostic sexually transmitted infection (STI) testing in low- and middle-income countries, and availability of targeted STI testing has been hypothesized to influence PrEP use. We evaluated the association of STI testing modality and PrEP uptake among pregnant women in antenatal care. Methods We enrolled pregnant, HIV-uninfected women (16 years or older) at their first antenatal visit with follow-up through 12 months postpartum. Women were offered oral PrEP and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using a point-of-care (POC; Cepheid, August 2019–November 2020) or laboratory-based (Thermofisher, December 2020–October 2021) test. We compared the proportion of women initiating and continuing PrEP by STI test adjusting for confounders. Results We evaluated 1194 women (median age, 26 years [interquartile range, 22–31 years]) with an STI result (46% POC and 54% laboratory-based). The prevalence of any STI was the same in POC-tested (28%) and laboratory-tested (28%) women—25% versus 23% for C. trachomatis (P = 0.35) and 7% versus 9% for N. gonorrhoeae (P = 0.11). Mean time from testing to result was 0 day for POC and 26 days for laboratory testing, and mean time from testing to treatment was 3 days for POC and 38 days for laboratory testing. Receiving a POC STI test was associated with higher PrEP initiation compared with women receiving a laboratory-based test (90% vs. 78%; adjusted odds ratio, 2.1; 95% confidence interval, 1.5–2.9), controlling for age, gravidity, STI diagnosis, intimate partner violence, gestational age, employment, HIV risk perception, and cohabiting status. Conclusions Point-of-care STI testing, offering same-day results and treatment initiation, may increase PrEP initiation among pregnant women in antenatal care.

Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: implications for oral pre-exposure prophylaxis roll out

BackgroundOral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use.MethodsWe conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020–March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV.ResultsWe enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22–31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16–30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34–1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65–2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0–0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68–100%). Specificity was 100% (95% CI = 99.67–100%).ConclusionThe prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

Maternal overweight and obesity and its associated factors and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected black South African pregnant women.

This study aimed to investigate various variables between maternal overweight and/or obesity versus normal-weight pregnant black South African women living with and without human immunodeficiency virus (HIV). A cross-sectional study design was employed. A total of 200 pregnant women were enrolled in the study, categorized according to body mass index (BMI) (kg/m2 ) into two groups: (1) overweight/obese (≥25 kg/m2 ) (n=97); and (2) nonoverweight/nonobese (<25 kg/m2 ) (n=103), where 90 were HIV-infected and 110 were HIV-uninfected. The differences between the maternal BMI categories were assessed using Fisher's exact t-test and the χ2 test. Simple and multiple logistic regression analyses were used to determine factors associated with maternal overweight and obesity. Multiple logistic regression analysis showed that maternal age (odds ratio [OR]: 1.061; 95% confidence interval [CI] 1.008-1.117; p=0.023) and gestational age (OR: 1.121; 95% CI 1.005-1.251; p=0.041) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. For maternal health outcomes, multiple logistic regression analysis showed that hypertensive disorders (OR: 0.273; 95% CI 0.124-0.601; p=0.001) and anemia (OR: 2.420; 95% CI 1.283-4.563; p=0.006) were significantly associated with maternal overweight/obesity in both HIV-infected and HIV-uninfected. The overweight/obese HIV-infected participants (OR: 0.233; 95% CI 0.075-0.717; p=0.011) had increased odds for developing hypertensive disorders compared to HIV-uninfected overweight/obese participants (OR: 0.471; 95% CI 0.172-1.291; p=0.143). Maternal overweight/obesity in both HIV-infected and HIV-uninfected pregnant black South African women was significantly associated with maternal age, gestational age, HPT disorders, and anemia. Maternal overweight/obesity decreased the odds for anemia, but increased the odds for the development of HPT disorders, especially in the HIV-infected pregnant women.

Sexual Risk among Pregnant Women at Risk of HIV Infection in Cape Town, South Africa: What Does Alcohol Have to Do with It?

This study examines baseline associations between alcohol use and HIV sexual risk among a cohort of HIV-uninfected pregnant women (n = 1201) residing in a high HIV burdened community in Cape Town,South Africa. Alcohol use was measured using a modified version of the Alcohol Use Disorder Identification Test (AUDIT). HIV sexual risk was measured through a composite variable of four risk factors: diagnosis with a STI, self-report of > 1 recent sex partners, partner HIV serostatus (unknown or HIV+) and condomless sex at last sex. Any past year alcohol use prior to pregnancy was reported by half of participants (50%); 6.0% reported alcohol use during pregnancy. Alcohol use prior to pregnancy was associated with increased odds of being at high risk of HIV (aOR = 1.33, 95% CI 1.05-1.68, for 2 risks and aOR = 1.47, 95% CI 0.95-2.27 for 3 risks). In addition to reducing alcohol use, several other strategies to address HIV sexual risk were identified. Evidence-based interventions to address alcohol use and other HIV sexual risk behaviors during pregnancy in South Africa are desperately needed. Qualitative work exploring individual and community level drivers of alcohol use among pregnant and breastfeeding women in this setting could support development of a culturally tailored intervention to address these issues in this population.

Defective Monocyte Enzymatic Function and an Inhibitory Immune Phenotype in Human Immunodeficiency Virus-Exposed Uninfected African Infants in the Era of Antiretroviral Therapy.

BackgroundHuman immunodeficiency virus-exposed uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa and are highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated whether human immunodeficiency virus (HIV)-exposure dysregulates HEU immunity, vaccine-antibody production, and human herpes virus amplify this effect.MethodsThirty-four HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort and observed up to 6 weeks of age; and then a subsequent 43 HIV-infected and 61 HIV-uninfected mother-infant pairs were recruited into a longitudinal infant cohort at either: 5–7 to 14–15; or 14–15 to 18–23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HIV-unexposed uninfected (HU) infants.ResultsWe demonstrate (1) altered monocyte phagosomal function and B-cell subset homeostasis and (2) lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-tetanus toxoid immunoglobulin G titers in HEU compared with HU infants. Human herpes virus infection was similar between HEU and HU infants.ConclusionsIn the era of antiretroviral therapy-mediated viral suppression, HIV exposure may dysregulate monocyte and B-cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

Low seroprevalence of hepatitis E virus in pregnant women in an urban area near Pretoria, South Africa

Hepatitis E virus (HEV) infection is a globally neglected health problem with a high burden in resource-poor communities. Pregnant women are at increased risk of complications. This pilot study sought to assess the seroprevalence of HEV infection in pregnant women at Dr George Mukhari Academic Hospital, South Africa. Stored serum samples from 384 HIV-uninfected pregnant women attending the antenatal clinic were initially screened for HEV total antibody. Positive samples were further evaluated for the presence of IgG and IgM antibody isotypes, using commercial ELISA assays. HEV RNA was assessed in antibody-positive samples utilizing qRT-PCR assay. The sample consisted of women with a median age of 31 years (interquartile range: 28-35 years). Total HEV antibody was detected in 12/384 (3.13%, 95% CI: 1.80-5.38) of these pregnant women. All 12 samples were IgG HEV antibody positive, but none tested positive for IgM antibody or for HEV RNA, demonstrating a lack of current or recent exposure. Our study revealed a low seroprevalence of HEV among pregnant women from an urban area north of Pretoria. This observation warrants further attention to the circulation of HEV in this population, and a greater understanding of the epidemiology of the infection in South Africa.

Vaginal Microbiota, Genital Inflammation and Extracellular Matrix Remodelling Collagenase: MMP-9 in Pregnant Women With HIV, a Potential Preterm Birth Mechanism Warranting Further Exploration.

BackgroundPregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria.Material and MethodsCervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, combination antiretroviral therapy (cART) exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA amplicon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored.ResultsCVF was available for 50 PWLWH (108 samples) and 12 HUPW (20 samples) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p<0.001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1β, IL-8, IL-12 and TNF-α in both trimesters compared to HUPW (p ≤ 0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1β (r=0.61), IL-8 (r=0.57) and TNF-α (r=0.64), p<0.001, similarly for TIMP-1. Abundance of anaerobic pathobionts correlated with MMP-9: Gardnerella (r=0.44, p<0.001), Atopobium (r=0.33, p=0.005), and Prevotella genera (r=0.39, p<0.001). Conversely proportion of Lactobacillus genera negatively correlated with MMP-9 (rho=-0.46, p<0.001). MMP-9/TIMP-1 ratio increased with gestational age at sampling in PWLWH, but this was no longer significant after adjusting for confounders and no difference by prematurity was observed in this sub-study.ConclusionsHere we show strong correlations of MMP-9 to genital tract inflammation and sub-optimal bacterial genera in PWLWH indicating the ascending genital tract infection pathway may be a contributory mechanism to the high risk of PTB.

Seroprevalence of Listeria monocytogenes in HIV infected pregnant women from Brazil

ObjectiveTo describe the prevalence and factors associated with serologic response to Listeria monocytogenes in HIV infected and uninfected pregnant women in Brazil. MethodsCross-sectional study, pregnant women after 14 weeks of gestational age were enrolled. Positive serologic test for L. monocytogenes was defined as titers >1:80 (agglutination test). Comparisons were performed using logistic regression. ResultsA total of 213 women were enrolled, 73 (34%) were HIV infected. 55 women were seroreactive for L. monocytogenes, 27 (37%) HIV-infected and 28 (20%) HIV-uninfected (p < 0.01). Considering the diet record, white cheese consumption was associated with seroreactivity (p < 0.01). In the group of pregnant women living with HIV, the variables associated with L. monocytogenes positive serology were: lower CD4+ cells count at study entry OR=4.8 (95%CI=1.1–19.8) and having neonates admitted to the intensive care unit OR=5.9 (95%CI=1.01–34.9). ConclusionPositive serology for Listeria monocytogenes was associated with HIV infection. Brazilian women should avoid white cheese during pregnancy.

Sexual Risk Behavior in HIV-Uninfected Pregnant Women in Western Uganda

Our aim was to identify sexual risk behavior among HIV-negative pregnant women in Kabarole District, Uganda, by conducting a cross-sectional study among 1610 women within three healthcare settings. One in six women engaged in HIV-specific risk behaviors including multiple sexual partners or alcohol abuse; 80% of the pregnant women reported to generally abstain from using condoms. In multivariate analysis, predictors of sexual risk behavior included being a client of the public health facilities as compared to the private facility (AOR 3.6 and 4.8, p < 0.001), being single, widowed or divorced or not cohabiting with the partner (AOR 4.7 and 2.3, p < 0.001), as well as higher household wealth (AOR 1.8, p < 0.001) and lack of partner status knowledge (AOR 1.6, p = 0.008). Self-estimated risk perception was linked with engagement in HIV-related risk behaviors except for alcohol abuse. Our findings indicate that reducing risky behaviors in pregnancy in order to prevent HIV should be a high-priority public health concern.

Alcohol use and intimate partner violence in HIV-uninfected pregnant women in Cape Town, South Africa

ABSTRACT In settings with a high burden of HIV, pregnant women often experience a cluster of risk factors, including alcohol use and intimate partner violence (IPV). These interrelated risks are poorly understood among pregnant women at risk of HIV in sub-Saharan Africa. We aim to determine cross-sectional associations between pregnant women’s alcohol use and victimization due to IPV in the HIV-Unexposed-Uninfected Mother-Infant Cohort Study in Cape Town, South Africa. Women who tested HIV-negative at first antenatal care (ANC) visit were followed to delivery. Trained interviewers collected demographic and psychosocial information, including recent alcohol use and experiences of IPV victimization. We assess the prevalence of alcohol use and associations with IPV using multivariable logistic regression. In 406 HIV-uninfected pregnant women (mean age = 28 years; mean gestational age = 21 weeks), 41 (10%) reported alcohol consumption in the past 12 months; 30/41 (73%) of these at hazardous levels. Any and hazardous alcohol use were associated with greater odds of reporting past year IPV (adjusted odds ratio [aOR] for hazardous use: 3.24, 95% CI = 1.11, 7.56; aOR for any alcohol use: 2.97, 95% CI = 1.19, 7.45). These data suggest the occurrence of overlapping HIV risk factors among pregnant women and may help design improved health interventions in this population.

Distinct cord blood C-peptide, adipokine, and lipidomic signatures by in utero HIV exposure.

Background:Early-life metabolic derangements in HIV-exposed uninfected (HEU) infants have been reported.Methods:Pregnant women with HIV and HIV-uninfected pregnant women were enrolled with their newborns in a US cohort from 2011–15. We measured cord insulin, C-peptide, and metabolic cytokines of HEU and HIV-unexposed uninfected (HUU) newborns using ELISA and metabolites, lipid subspecies, and eicosanoids via liquid chromatography/mass spectrometry. Linear regression was employed to assess the association of intrauterine HIV/ART with insulin and C-peptide. Graphical lasso regression was used to identify differences between metabolite/lipid subspecies networks associated with C-peptide.Results:Of 118 infants, 56 were HEU, ART-exposed. In adjusted analyses, mean cord insulin (β=0.295, p=0.03) and C-peptide (β=0.522, p<0.01) were significantly higher in HEU vs. HUU newborns. HEU neonates exhibited primarily positive associations between complex lipids and C-peptide, indicative of fuel storage, and augmented associations between cord eicosanoids and cytokines. HUU neonates exhibited negative associations with lipids and C-peptide indicative of increased fuel utilization.Conclusion:Higher cord insulin and C-peptide in HEU vs. HUU newborns as well as differences in cord metabolites, metabolic-related cytokines, and eicosanoids may reflect a propensity for fuel storage and an inflammatory milieu suggestive of fetal metabolic changes associated with in utero HIV/ART exposure.

Maternal PrEP Use in HIV-Uninfected Pregnant Women in South Africa: Role of Stigma in PrEP Initiation, Retention and Adherence.

Pregnant women in sub-Saharan Africa are at high risk of HIV acquisition and require effective methods to prevent HIV. In a cohort of pregnant women offered Pre-exposure prophylaxis (PrEP), we evaluate the relationship between internalized and anticipated stigma and PrEP initiation at first antenatal visit, 3-month continuation and adherence using multivariable logistic regression. High internalized and anticipated PrEP stigma are associated with lower PrEP care initiation at first antenatal visit (aOR internalized stigma = 0.06; 95% CI = 0.03–0.11 and aOR anticipated stigma = 0.55; 95% CI = 0.31–1.00) compared to women with low reported stigma, after controlling for covariates. Women whose partners have not been tested for HIV or whose serostatus remains unknown have 1.6-times odds of PrEP retention at 3-months compared to women whose partners have been tested (aOR = 1.60; 95% CI = 1.02–2.52) after adjusting for covariates. PrEP counseling and maternal PrEP interventions must consider individual- and relational-level interventions to overcome anticipated PrEP stigma and other barriers to PrEP initiation and adherence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10461-021-03374-x.

Lactobacillus-Depleted Vaginal Microbiota in Pregnant Women Living With HIV-1 Infection Are Associated With Increased Local Inflammation and Preterm Birth.

BackgroundPregnant women living with HIV-1 infection (PWLWH) have an elevated risk of preterm birth (PTB) of unknown aetiology, which remains after successful suppression of HIV. Women at high risk for HIV have a common bacterial profile which has been associated with poor birth outcomes. We set out to explore factors associated with gestational age at delivery of PWLWH in a UK population.MethodsProspective study of PWLWH (n = 53) in whom the vaginal microbiota and cervicovaginal cytokine milieu were assessed using metataxonomics and multiplexed immunoassays, respectively. Cross-sectional characterisation of vaginal microbiota in PWLWH were compared with 22 HIV uninfected pregnant women (HUPW) at a similar second trimester timepoint. Within PWLWH the relationships between bacterial composition, inflammatory response, and gestational age at delivery were explored.FindingsThere was a high rate of PTB among PWLWH (12%). In the second trimester the vaginal microbiota was more diverse in PWLWH than in HUPW (Inverse Simpson Index, p = 0.0004 and Species Observed, p = 0.009). PWLWH had a lower prevalence of L. crispatus dominant vaginal microbiota group (VMB I, 15 vs 54%) than HUPW and higher prevalence of L. iners dominant (VMB III, 36 vs 9% and VMB IIIB, 15 vs 5%) and mixed anaerobes (VMB IV, 21 vs 0%). Across the second and third trimesters in PWLWH, VMB III/IIIB and IV were associated with PTB and with increased local inflammation [cervicovaginal fluid (CVF) cytokine concentrations in upper quartile]. High bacterial diversity and anaerobic bacterial abundance were also associated with CVF pro-inflammatory cytokines, most notably IL-1β.InterpretationThere is an association between local inflammation, vaginal dysbiosis and PTB in PWLWH. Understanding the potential of antiretroviral therapies to influence this cascade will be important to improve birth outcomes in this population.