HIV-uninfected Women Research Articles

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines

ObjectivesRecent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed...

Comparison of HPV detection in HIV-infected and HIV-uninfected Kenyan women with or without cervical dysplasia.

e17015 Background: Cervical cancer, a malignancy caused by human papillomavirus (HPV) infection, is the most common malignancy in women living in sub-Saharan African countries including Kenya. HIV co-infection accelerates the natural course of cervical cancer. To determine the specific HPV type distribution in HIV-infected women compared to HIV-uninfected women, with and without evidence of cervical dysplasia. Methods: Demographic information, behavioral data, and a cervical swab were collected from women 18 and 45 years of age, HIV-infected or HIV-uninfected, who presented for cervical cancer screening at Moi Referral and Teaching Hospital in Eldoret, Kenya. Women were triaged based on the presence or absence of cervical dysplasia. HPV testing was performed using the Roche Linear Array Assay. Results were compared between women with or without HIV co-infection and between those with or without cervical dysplasia, using Chi-square tests or Fisher’s exact tests. Results: 223 women had normal VIAs. All had HPV testing, 221 had valid results: 115 HIV-infected women (mean age 37 years) and 106 HIV-uninfected (mean age 33 years). 175 women had abnormal VIAs. 143 women had HPV testing performed, 140 had valid results: 70 HIV-infected women (mean age 38.5 years) and 70 HIV-uninfected (mean age 31.3 years). Greater than 90% of all HIV-infected women in both projects were receiving anti-retroviral therapy at enrollment. HPV of any type was detected in 48% of all women with normal VIA vs. 61% of women with abnormal VIA (P = 0.018). High risk (HR)-HPV was detected in 38% of all women with normal VIA vs. 51% of all women with abnormal VIA (P = 0.012). HIV-uninfected women with normal VIA had significantly lower detection of all HPV (P = 0.026), high risk-HPV (P = 0.018), IARC high risk-HPV (P = 0.047), A9 types (P = 0.050), and individual types HPV 16 (P = 0.0274), HPV 18 (P = 0.007), and HPV 51 (P = 0.009) than HIV-uninfected women with abnormal VIA. Among HIV-infected women, there was no difference in detection of any group of HPV types or individual types with respect to VIA results. Conclusions: HIV-uninfected women without cervical dysplasia had lower detection of oncogenic HPV than HIV-uninfected women with dysplasia. In contrast, HPV detection did not differ among HIV-infected women between those with or without cervical dysplasia. In addition, VIA appears to lack specificity for HPV-associated cervical dysplasia, as 39% of women with abnormal VIA examinations did not have any HPV detected, and 49% of women with abnormal VIA examinations did not have any HR-HPV detected.

Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.

Asymptomatic Bacterial Vaginosis in Pregnancy and Missed Opportunities for Treatment: A Cross-Sectional Observational Study.

Background High rates of bacterial vaginosis (BV) have been described in nonpregnant South African women. Studies of BV in South African pregnant women are sparse. Diagnosis and prompt treatment of BV in pregnancy are expected to have a positive impact on pregnancy outcomes and HIV prevention. This study was undertaken to determine the prevalence of BV in pregnant women in a high HIV burden periurban setting in KwaZulu-Natal and explore how to enhance BV diagnosis in this setting where syndromic management of sexually transmitted diseases is the standard of care. Methods In this cross-sectional study, consenting HIV uninfected pregnant women were examined for abnormal vaginal discharge; nurses determined the vaginal pH and collected a vaginal swab for Gram-stain and Nugent scoring. Findings Among 750 HIV uninfected pregnant women, 280 (37.3%; 95%CI 33.9-40.9) tested positive for BV. Using a vaginal pH > 4.4, 65% of women with BV were correctly identified, while an abnormal vaginal discharge correctly identified a significantly lower proportion (52.9%) of women with BV (p=0.005). The sensitivity, specificity, and positive and negative predictive values of vaginal pH testing were 65.9% (95%CI 60.0 – 71.5%), 61.4% (95%CI 56.8 – 65.9%), and 50.1% and 75.4%, respectively. The 20-24 year-old pregnant women were twice more likely to test positive for BV than the adolescent pregnant women (43.6% vs 21.1%) (p = 0.037) and BV was not associated with the duration of a sexual relationship, frequency of unprotected sex during pregnancy, number of lifetime sex partners, or the partner's age. Conclusion There is a high burden of primarily asymptomatic BV in HIV uninfected pregnant women in this periurban setting. Both the sensitivity and specificity of vaginal pH testing are superior to the symptomatic diagnosis of BV but not good enough to be used as a screening tool.

Lipid based nutrient supplements during pregnancy may improve foetal growth in HIV infected women - A cohort study.

ObjectivesBoth maternal HIV infection and antiretroviral therapy are associated with adverse birth outcomes. The role of antenatal nutrient supplements with regard to adverse birth outcomes in HIV infected women exposed to antiretroviral therapy is not well known. We assessed the association between HIV and birth outcomes and explored whether antenatal lipid-based nutrient supplements (LNS) modulated this association.MethodsWe analysed a nested cohort of pregnant Malawian women who received daily LNS, multiple micronutrients (MMN) or iron and folic acid (IFA). Birth weight, length-for-age z-score (LAZ) and weight-for-age z-score (WAZ) were analysed as continuous outcomes and proportion of stunting and small-for-gestational age (SGA) as dichotomous outcomes.Results134 HIV infected (46 LNS, 39 MMN, 49 IFA) and 833 HIV uninfected (271 LNS, 287 MMN, 275 IFA) women were included. Maternal HIV infection was associated with a lower mean birth weight (-129g (-209, -48), P = 0.002); LAZ (-0.34 (-0.54, -0.13), P = 0.002) and WAZ (-0.21 (-0.40, -0.02), P = 0.041) and a higher risk of stunting (RR (95% confidence interval), 1.87 (1.24, 2.83), P = 0.003) and SGA (1.66 (1.21, 2.26), P = 0.001) in the newborn. If the women received LNS, HIV was not associated with LAZ (mean difference (95%); -0.02 (-0.35, 0.31), P = 0.918) or newborn stunting (RR (95% CI), 0.84 (0.34, 2.03), P = 0.691). However HIV tended to be associated with LAZ if the women received MMN (-0.42 (-0.80, -0.03), P = 0.053); and was significantly associated with LAZ if the women received IFA (-0.52 (-0.89, -0.14), P = 0.021) and with newborn stunting if they received MMN (2.40 (1.15, 4.98), P = 0.029) or IFA (2.40 (1.26, 4.59), P = 0.024).ConclusionsFurther research to investigate the impact of LNS on various aspects of foetal growth in HIV infected women is warranted.

Maternal Perinatal HIV Infection Is Associated With Increased Infectious Morbidity in HIV-exposed Uninfected Infants.

The aging population of females with perinatally-acquired HIV (PHIV) are having their own children. HIV-exposed uninfected infants (HEU-N) born to women living with non-perinatally-acquired HIV (NPHIV) experience higher infectious morbidity compared with HIV-unexposed infants (HUU). Little is known about the infectious morbidity risk of HIV-exposed uninfected infants (HEU-P) born to PHIV women. We evaluated prevalence of infectious cause hospitalizations (ICH) during the first year of life among HEU-P, HEU-N and HUU infants in a United States (U.S) tertiary care center. Maternal HIV status was categorized as PHIV vs. NPHIV vs. HIV-uninfected. Generalized Estimating Equation models were fit to evaluate the association between maternal HIV status and infant ICH. ICH was evaluated among 205 infants, 28 HEU-P infants, 112 HEU-N infants, and 65 HUU infants. PHIV women were younger compared with NPHIV and HIV-uninfected women (median age 22 years vs. 29 and 23 respectively, p<0.01). Overall, 21% of HEU-P, 4% of HEU-N and 12% of HUU infants experienced at least one ICH event (p<0.01) in the first year of life. After adjusting for confounders, HEU-P infants were at increased ICH risk compared with HEU-N infants [adjusted odds ratio (aOR)=7.45, 95% Confidence Interval (CI):1.58-35.04]. In sub-group analysis of HEU infants, excluding HUU infants, this relationship persisted after adjustment for maternal CD4 and HIV RNA level (aOR=10.24, 95% CI:1.66-63.31) CONCLUSIONS:: In a small U.S. cohort, HEU-P infants experienced increased ICH risk. Differences in intrauterine environments, social factors, or access to care may be important factors to assess in future larger studies.

A cross-sectional analysis of factors associated with detection of oncogenic human papillomavirus in human immunodeficiency virus-infected and uninfected Kenyan women

BackgroundCervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women.MethodsWomen without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher’s exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software.ResultsCompared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007–1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1.206–8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764–0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565–0.883) were associated with reduced detection.ConclusionHIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.

Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study

BackgroundMalaria in pregnancy is a major public health challenge, but its risk factors remain poorly understood in some settings. This study assessed the association between household and maternal characteristics and malaria among pregnant women in a high transmission area of Uganda.MethodsA nested prospective study was conducted between 6th September 2016 and 5th December 2017 in Busia district. 782 HIV uninfected women were enrolled in the parent study with convenience sampling. Socioeconomic and house construction data were collected via a household survey after enrolment. Homes were classified as modern (plaster or cement walls, metal or wooden roof and closed eaves) or traditional (all other homes). Maternal and household risk factors were evaluated for three outcomes: (1) malaria parasitaemia at enrolment, measured by thick blood smear and qPCR, (2) malaria parasitaemia during pregnancy following initiation of IPTp, measured by thick blood smear and qPCR and (3) placental malaria measured by histopathology.ResultsA total of 753 of 782 women were included in the analysis. Most women had no or primary education (75%) and lived in traditional houses (77%). At enrolment, microscopic or sub-microscopic parasitaemia was associated with house type (traditional versus modern: adjusted risk ratio (aRR) 1.29, 95% confidence intervals 1.15–1.45, p < 0.001), level of education (primary or no education versus O-level or beyond: aRR 1.13, 95% confidence interval 1.02–1.24, p = 0.02), and gravidity (primigravida versus multigravida: aRR 1.10, 95% confidence interval 1.02–1.18, p = 0.009). After initiation of IPTp, microscopic or sub-microscopic parasitaemia was associated with wealth index (poorest versus least poor: aRR 1.24, 95% CI 1.10–1.39, p < 0.001), house type (aRR 1.14, 95% CI 1.01–1.28, p = 0.03), education level (aRR 1.19, 95% CI 1.06–1.34, p = 0.002) and gravidity (aRR 1.32, 95% CI 1.20–1.45, p < 0.001). Placental malaria was associated with gravidity (aRR 2.87, 95% CI 2.39–3.45, p < 0.001), but not with household characteristics.ConclusionsIn an area of high malaria transmission, primigravid women and those belonging to the poorest households, living in traditional homes and with the least education had the greatest risk of malaria during pregnancy.

PG-1 Compromised growth among HIV exposed compared to unexposed children in Nigeria

Introduction: HIV exposed but uninfected (HEU) children may be at an increased risk of impaired growth and development when compared to their unexposed and uninfected (HUU) counterparts. We compared growth pattern between HEU and HUU children in Nigeria. Methods: HIV infected and uninfected pregnant women were enrolled at the Plateau State Specialist Hospital (PSSH) Jos Nigeria. Babies born to these mothers were recruited at birth and the mother-infant pairs followed up until 18 months. Weight, length, and head circumference of the babies were measured at each study visit. Age and gender standardized z scores were generated for each anthropometric measure using the World Health Organization Child Growth Standards. Children with length for age (LAZ), weight for age (WAZ) and weight for length (WLZ) z scores &lt;−2 were classified as stunted, underweight, and wasted respectively. Results: A total of 415 children (307 HEU and 108 HUU) were included in this analysis. At birth, 117 (28.4%), 9 (2.2%) and 32 (7.8%) babies were stunted, underweight and wasted respectively. In a multivariable longitudinal analysis, the odds of stunting was higher among HEU as compared to HUU children (OR: 2.4 [95% CI: 1.4 to 4.1]; P = 0.001). Similarly, odds of being underweight was higher among the HEU children (OR: 1.6 [95% CI: 1.1 to 2.2]; P = 0.009). While the odds of wasting appeared higher for the HEU children (OR: 1.5 [95% CI: 0.9 to 2.4]; P = 0.128), the difference did not reach statistical significance. Conclusions: We found strong evidence of greater impairment of linear and ponderal growth among HEU as compared to HUU children during the first 18 months of life in Nigeria. Further studies are needed to explore the causal basis for these differences.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil.Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed.Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7–39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%).Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.

MAIT cells, TCR γδ+ cells and ILCs cells in human breast milk and blood from HIV infected and uninfected women.

Human breast milk cells remain poorly characterized for the presence of unconventional T lymphocytes and innate lymphoid cells (ILCs). Early breast milk was collected from eight HIV-uninfected and 11 HIV-infected women 3-12days after delivery. Mucosal-associatedinvariant T cells (MAIT cells), TCR γδ cells, and innate lymphoid cells (ILCs) were analyzed in breast milk and paired blood samples. CD161+/TRAV1-2+MAIT cells were detected in breast milk, accounting for a median (IQR) of 0.08% (0.06-0.16) and 0.17% (0.16-0.31) of CD45+ breast milk cells in HIV-uninfected and HIV-infected women, respectively. A selective compartmentalization of γδ T lymphocytes was observed in breast milk. Median (IQR) frequency of γδ T lymphocytes was 8.95% (8.64-12.14) among breast milk lymphocyte cells compared to 2.54% (1.81-4.10) in blood (P=0.03) in HIV-uninfected women, and 7.26% (4.22-10.54) in breast milk versus 3.31% (2.54-3.80) in blood (P=0.004) from HIV-infected women. The proportion of group 1 ILC (ILC1) among total ILCs was higher in breast milk compared to blood in HIV-uninfected women (P=0.03) and HIV-infected women (P=0.001). The frequency of ILC2 among total ILCs tends to be lower in breast milk compared to blood in HIV-uninfected women (P=0.06) and HIV-infected women (P=0.03). Unconventional T cells and ILCs that may be involved in both the protection against infection of the lactating mammary gland and maturation of infant's gut and microbiomes account for a detectable fraction of breast milk cells.

Monthly sulfadoxine–pyrimethamine versus dihydroartemisinin–piperaquine for intermittent preventive treatment of malaria in pregnancy: a double-blind, randomised, controlled, superiority trial

Intermittent treatment with sulfadoxine-pyrimethamine, recommended for prevention of malaria in pregnant women throughout sub-Saharan Africa, is threatened by parasite resistance. We assessed the efficacy and safety of intermittent preventive treatment with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. We did a double-blind, randomised, controlled, superiority trial at one rural site in Uganda with high malaria transmission and sulfadoxine-pyrimethamine resistance. HIV-uninfected pregnant women between 12 and 20 weeks gestation were randomly assigned (1:1) to monthly intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine. The primary endpoint was the risk of a composite adverse birth outcome defined as low birthweight, preterm birth, or small for gestational age in livebirths. Protective efficacy was defined as 1-prevalence ratio or 1-incidence rate ratio. All analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02793622. Between Sept 6, 2016, and May 29, 2017, 782 women were enrolled and randomly assigned to receive sulfadoxine-pyrimethamine (n=391) or dihydroartemisinin-piperaquine (n=391); 666 (85·2%) women who delivered livebirths were included in the primary analysis. There was no significant difference in the risk of our composite adverse birth outcome between the dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine treatment group (54 [16%] of 337 women vs 60 [18%] of 329 women; protective efficacy 12% [95% CI -23 to 37], p=0·45). Both drug regimens were well tolerated, with no significant differences in adverse events between the groups, with the exception of asymptomatic corrected QT interval prolongation, which was significantly higher in the dihydroartemisinin-piperaquine group (mean change 13 ms [SD 23]) than in the sulfadoxine-pyrimethamine group (mean change 0 ms [SD 23]; p<0·0001). Monthly intermittent preventive treatment with dihydroartemisinin-piperaquine was safe but did not lead to significant improvements in birth outcomes compared with sulfadoxine-pyrimethamine. Eunice Kennedy Shriver National Institute of Child Health and Human Development, and Bill & Melinda Gates Foundation.

A High-throughput Bead-based Affinity Assay Enables Analysis of Genital Protein Signatures in Women At Risk of HIV Infection

Women at high risk of HIV infection, including sex workers and those with active genital inflammation, have molecular signatures of immune activation and epithelial barrier remodeling in samples of their genital mucosa. These alterations in the local immunological milieu are likely to impact HIV susceptibility. We here analyze host genital protein signatures in HIV uninfected women, with high frequency of condom use, living in HIV-serodiscordant relationships. Cervicovaginal secretions from women living in HIV-serodiscordant relationships (n = 62) were collected at three time points over 12 months. Women living in HIV-negative seroconcordant relationships (controls, n = 25) were sampled at one time point. All study subjects were examined for demographic parameters associated with susceptibility to HIV infection. The cervicovaginal samples were analyzed using a high-throughput bead-based affinity assay. Proteins involved in epithelial barrier function and inflammation were increased in HIV-serodiscordant women. By combining several methods of analysis, a total of five proteins (CAPG, KLK10, SPRR3, elafin/PI3, CSTB) were consistently associated with this study group. Proteins analyzed using the affinity set-up were further validated by label-free tandem mass spectrometry in a partially overlapping cohort with concordant results. Women living in HIV-serodiscordant relationships thus had elevated levels of proteins involved in epithelial barrier function and inflammation despite low prevalence of sexually transmitted infections and a high frequency of safe sex practices. The identified proteins are important markers to follow during assessment of mucosal HIV susceptibility factors and a high-throughput bead-based affinity set-up could be a suitable method for such evaluation.

Physical Functioning Among Patients Aging With Human Immunodeficiency Virus (HIV) Versus HIV Uninfected: Feasibility of Using the Short Physical Performance Battery in Clinical Care of People Living With HIV Aged 50 or Older.

BackgroundThe Short Physical Performance Battery (SPPB) is a well regarded physical functioning assessment including balance, gait speed, and chair-stand tests. Its use has not been widely assessed in human immunodeficiency virus (HIV) care. We evaluated the feasibility of integrating the SPPB into care of aging people living with HIV (PLWH) and compared SPPB performance with aged HIV-uninfected individuals.MethodsWe enrolled PLWH aged ≥50 at 3 HIV clinics and compared their SPPB scores and subscores with older HIV-uninfected adults in the Health, Aging, and Body Composition (Health ABC) study. We conducted regression analyses on age stratified by sex and adjusting for site, and we calculated percentage variance explained by age among PLWH and HIV-uninfected adults.ResultsThe SPPB was feasible to implement in clinical care and did not require licensed professionals; 176 PLWH completed it with a mean completion time of 7.0 minutes (standard deviation = 2.6). Overall mean SPPB score among PLWH was 10.3 (median 11.0, 25th percentile 9.0, 75th percentile 12.0). People living with HIV were younger than HIV-uninfected individuals (55 vs 74 years old). Mean SPPB scores and most subscores were similar among PLWH and older HIV-uninfected individuals despite the ~20-year age difference. Regression analyses of gait speed revealed similar slopes in PLWH and HIV-uninfected individuals; however, separate intercepts were needed for PLWH. Mean gait speeds were faster in older HIV-uninfected men and women (P < .01), yet relationships with age within PLWH and HIV uninfected were similar.ConclusionsThe SPPB can be implemented into busy HIV clinics. Despite the ~20-year age difference, mean scores were similar among PLWH and older HIV-uninfected individuals, although gait speed was faster among HIV-uninfected individuals.

Increased Cervical CD4+CCR5+ T Cells Among Kenyan Sex Working Women Using Depot Medroxyprogesterone Acetate.

Depot medroxyprogesterone acetate (DMPA) is the most common hormonal contraceptive used by women in sub-Saharan Africa, however, it has been epidemiologically associated with HIV infections. To assess whether DMPA has an effect on the number and activation of HIV target cells, this study assessed the levels and phenotype of blood- and mucosal-derived HIV target cells among women using DMPA. Thirty-five HIV uninfected women from the Pumwani Sex Worker cohort from Nairobi, Kenya were enrolled in the study (15 using DMPA and 20 not using hormonal contraception). Blood (plasma and peripheral blood mononuclear cells) and cervicovaginal (lavage, cervical cells, and ectocervical biopsies) samples were collected. Cellular phenotype and activation status were determined by flow cytometry, cytokine levels were assessed by bead array and image analysis assessed cell number and phenotype in situ. In blood, the proportion of HIV target cells and activated T cells was lower in DMPA users versus those not using hormonal contraceptives. However, analysis of cervical mononuclear cells showed that DMPA users had elevated levels of activated T cells (CD4+CD69+) and expressed lower levels of the HIV co-receptor CCR5 on a per cell basis, while tissue samples showed that in the ectocervix, DMPA users had a higher proportion of CD4+CCR5+ T cells. This study demonstrates that DMPA users had higher levels of activated T cells and HIV target cells in the genital tract. The increased pool of mucosal HIV target cells provides new biological information about the potential impact of DMPA on HIV susceptibility.

Primary HIV prevention in pregnant and lactating Ugandan women: A randomized trial.

BackgroundThe ‘Primary HIV Prevention among Pregnant and Lactating Ugandan Women’ (PRIMAL) study aimed to assess the effectiveness of an enhanced HIV counseling intervention for preventing HIV acquisition among HIV-uninfected mothers during pregnancy and throughout the breastfeeding period.MethodsWe conducted an unblinded randomized control trial between 22 February 2013 and 22 April 2016 to assess the effectiveness of an extended repeat HIV testing and enhanced counseling (ERHTEC) intervention aimed at preventing primary HIV infection among HIV-uninfected pregnant and lactating women in Uganda. HIV-uninfected pregnant women aged 15–49 were enrolled 1:1 individually or in couples together with their partner. Enrolled women and couples were randomized 1:1 to an intervention (ERHTEC) or control (extended repeat HIV testing and standard counseling) group and followed up to 24 months postpartum or six weeks past complete cessation of breastfeeding, whichever came first. Both groups were tested for sexually transmitted infections (STIs) and HIV at enrollment, delivery, 3 and 6 months postpartum and every 6 months thereafter until the end of follow-up. The intervention group received enhanced HIV prevention counseling every 3 months throughout follow-up. The control group received standard counseling at the time of HIV retesting. Both intervention and control couples were offered couple HIV testing and counseling at all study visits.Main outcome measuresFrequency of condom use and incidence of HIV, syphilis, gonorrhea, chlamydia and trichomoniasis over follow-up.ResultsBetween February 2013 and April 2014, we enrolled 820 HIV-uninfected pregnant women presenting for antenatal care individually (n = 410) or in couples (n = 410 women and 410 partners) in one urban and one rural public Ugandan hospital. Women’s median age was 24 years (IQR 20–28 years). At baseline, participants did not differ in any socio-demographic, reproductive health, HIV testing history, sexual behavior, medical history or STI status characteristics; 96% (386/402) of couples were tested and counseled for HIV together with their partners at enrolment, 2.1% (7/329) of whom were found to be HIV-infected. Six hundred twenty-five (76%) women completed follow-up as per protocol (S1 Protocol). Women were followed for an average of 1.76 years and cumulated 1,439 women-years of follow-up or 81% of the maximum 1,779 women-years of follow-up assuming no dropouts. Men were followed for an average of 1.72 years.The frequency of consistent condom use and the proportion of women who used condoms over the last 3 months or at last vaginal sex increased substantially over follow-up in both arms, but there were no statistically significant differences in increases between the intervention and control arms.During follow-up, on average 42% (range 36%-46%) of couple partners were counseled together. Between 3.8% and 7.6% of women tested positive at any follow-up visit for any STI including syphilis, gonorrhea, C. trachomatis or T. vaginalis. Four women (two in each arm) and no enrolled men became infected with HIV, representing an overall HIV incidence rate of 0.186 per 100 person-years. Three of the women seroconverters had enrolled individually, one as a couple. At or before seroconversion, all four women reported their partners had extramarital relationships and/or had not disclosed their suspected HIV-infected status. There were no statistically significant differences between study arms for STI or HIV incidences.ConclusionsA sustained enhanced HIV prevention counseling intervention for up to 2 years postpartum among pregnant and breastfeeding women did not have a statistically significant effect on condom use or HIV incidence among these women. However, in both study arms, condom use increased over follow-up while STI and HIV incidence remained very low when compared to similar cohorts in and outside Uganda, suggesting that repeat HIV testing during breastfeeding, whether with enhanced or standard counseling, may have had an unintended HIV preventive effect among pregnant and lactating women in this setting. Further research is needed to verify this hypothesis.Trial registrationClinicalTrials.gov NCT01882998

Growth trajectories of breastfed HIV-exposed uninfected and HIV-unexposed children under conditions of universal maternal antiretroviral therapy: a prospective study

Over 1 million HIV-exposed uninfected (HEU) children are born in sub-Saharan Africa annually. Little data exist on the risk of impaired growth in this population under current policies of universal maternal antiretroviral therapy (ART) with breastfeeding. We aimed to study the growth of breastfed HEU children born to women who initiated ART during pregnancy and compare their growth with that of breastfed HIV-unexposed (HU) children drawn from the same community. A prospective cohort of HIV-uninfected and HIV-infected pregnant women, who were initiating ART, were enrolled at their first antenatal care visit in a primary care centre in Gugulethu, Cape Town, South Africa. HIV infected women were participants of the Maternal Child Health Antiretroviral Therapy (MCH-ART) study, and HIV-uninfected pregnant women were participants in the HIV-Unexposed-Uninfected (HU2) study. All women were followed up during pregnancy, through delivery, to the early postnatal visit, which was scheduled for the first week after birth. At this visit, eligible breastfeeding mother-child pairs were recruited for continuation of postnatal follow-up until approximately age 12 months. Child anthropometry was measured at around 6 weeks, and every 3 months from month 3 to month 12. Weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ), head circumference-for-age, and body-mass index-for-age Z scores were compared between HEU and HU children longitudinally using mixed effects linear regression. At 12 months, proportions of HEU and HU children with moderate or severe malnutrition were compared cross-sectionally using logistic regression. MCH-ART is registered with ClinicalTrials.gov, number NCT01933477. Between June, 2013, and April, 2016, 884 breastfeeding mothers and their newborn babies (HEU, n=471; HU, n=413) were enrolled into postnatal follow-up. Excluding 12 children who tested HIV positive during follow-up, 461 HEU and 411 HU children attended 4511 study visits in total, with a median of 6 visits (IQR 5-6) per child. Birth characteristics were similar (overall, 94 [11%] of 872 preterm [<37 weeks] and 90 [10%] small-for-gestational age [birthweight <10th percentile]). Median duration of breastfeeding was shorter among HEU than HU children (3·9 months [IQR 1·4-12·0] vs 9·0 months [IQR 3·0-12·0]). Although WAZ scores increased over time in both groups, HEU children had consistently lower mean WAZ scores than HU children (overall β -0·34, 95% CI -0·47 to -0·21). LAZ scores decreased in both groups after 9 months. At 12 months, HEU children had lower mean LAZ scores than HU children (β -0·43, -0·61 to -0·25), with a higher proportion of children stunted (LAZ score <-2: 35 [10%] of 342 HEU vs 14 [4%] of 342 HU children; odds ratio [OR] 2·67, 95% CI 1·41 to 5·06). Simultaneously, overweight (WLZ score >2) was common in both groups of children at 12 months (54 [16%] of 342 HEU vs 60 [18%] of 340 HU children; OR 0·87, 95% CI 0·58 to 1·31). Compared with HU children, HEU children have small deficits in early growth trajectories under policies of universal maternal ART and breastfeeding. Large proportions of both HEU and HU children were overweight by 12 months, indicating substantial risks for early onset obesity among South African children. Although the longer-term metabolic effects of ART exposure in the context of childhood obesity warrants further investigation, addressing childhood obesity should be an urgent public health priority in this setting. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, and the Fogarty Foundation.

Cisplatin and radiation therapy in HIV-positive women with locally advanced cervical cancer in sub-Saharan Africa: A phase II study of the AIDS malignancy consortium

PurposeTo determine the feasibility, safety, and tolerability of concomitant chemoradiotherapy administered at standard doses in HIV-infected women with locally-advanced cervical cancer (LACC) receiving antiretroviral therapy (ART). Patients and methodsEligible participants had HIV infection and untreated, histologically-confirmed, invasive carcinoma of the uterine cervix, FIGO stages IB2, IIA (if tumor >4 cm), IIB, IIIA, IIIB, or IVA and met standard eligibility criteria. Subjects were prescribed 41.4–45 Gy external beam radiation therapy followed by high dose rate brachytherapy concomitant with up to six weekly doses of cisplatin 40 mg/m2 and were followed for 12 months. ResultsSixty-four women were screened at two sites in sub-Saharan Africa, of whom 40 eligible participants were enrolled, for a screening ratio of 1.60. Of the 38 eligible participants who initiated study treatment, 31 (82%) completed treatment. By the 12-month follow-up visit, 7 women had died of disease and 29 of 31 (94%) returned for follow-up. One-year progression-free survival was 76.3% (95% CI, 59.4–86.9%), and did not significantly differ according to stage at entry (p = 0.581). Participant-reported adherence to ART was high; by 12 months, 93% of participants had an undetectable viral load. The most common grade 3 or 4 adverse event was decreased lymphocyte count that affected all treated participants. Non-hematologic serious adverse events were similar to those observed in women with LACC without HIV infection. ConclusionsThe majority of HIV-infected women with LACC can complete concomitant chemoradiotherapy with the same cisplatin dose used in HIV-uninfected women with comparable tolerability and high ART adherence while on treatment.

Association between vaginal washing and vaginal bacterial concentrations.

Vaginal washing is a common practice associated with adverse outcomes including bacterial vaginosis (BV) and HIV infection. Prior studies have not examined the associations between vaginal washing and individual vaginal bacteria, or whether these associations are independent of the effect of vaginal washing on BV. The purpose of this study was to characterize the association between vaginal washing and the presence and concentrations of vaginal bacteria associated with optimal and sub-optimal vaginal states. The analysis utilized data from participants in the placebo arm of the Preventing Vaginal Infections trial, which enrolled HIV-uninfected women from the United States and Kenya. Detection of bacterial taxa associated with BV was compared between visits with versus without reported vaginal washing. The effect of vaginal washing on a number of vaginal bacteria differed substantially (p<0.05) between the US and Kenya, so results were stratified by country. In US women, vaginal washing was associated with a significantly higher likelihood of detection of BV associated bacterium 1 (BVAB1) (relative risk [RR] 1.55, 95% confidence interval [CI] 1.15–2.09, p = 0.004), BVAB2 (RR 1.99, 95%CI 1.46–2.71, p<0.001), Mageeibacillus indolicus (RR 2.08, 95%CI 1.46–2.96, p<0.001), Atopobium vaginae (RR 1.34, 95%CI 1.13–1.59, p = 0.001), Leptotrichia/Sneathia species (RR 1.66, 95% CI 1.33–2.09, p<0.001), Megasphaera species (RR 1.78, 95%CI 1.34–2.37, p<0.001) and Gardnerella vaginalis (RR 1.08, 95%CI 1.01–1.16, p = 0.02). No significant association between vaginal washing and bacterial detection was found in Kenyan women. Adjustment for bacterial vaginosis diagnosed by Gram stain did not alter these results. This study provides evidence that the association between vaginal washing and detection of individual bacterial taxa can vary regionally. For some vaginal bacteria, the association with vaginal washing may be independent of the effect on Gram stain detection of BV. Larger prospective studies in diverse geographic settings should explore whether eliminating vaginal washing impacts the presence and concentrations of key vaginal bacteria.

Sexually transmitted infections during pregnancy and subsequent risk of stillbirth and infant mortality in Kenya: a prospective study

ObjectivesWe evaluated the relationship of sexually transmitted infections (STIs) and genital infections during pregnancy and subsequent risk for infant mortality and stillbirth.MethodsThis was a nested longitudinal analysis using data from...