RESUMEN
BACKGROUND: SARS-CoV-2 seropositivity data in women living with HIV (WLHIV), their infants and associated factors in this subpopulation remain limited. We retrospectively measured SARS-CoV-2 seropositivity from 07/2020-11/2021 among WLHIV and their children in the PROMOTE observational cohort in Uganda, Malawi, and Zimbabwe prior to widespread SARS-CoV-2 vaccination in those countries. METHODS: Plasma stored during 3 waves of the COVID-19 pandemic in East/Southern Africa were tested for SARS-CoV-2 specific IgG antibodies (Ab) using serological assays that detect adaptive immune responses to SARS-CoV-2 spike protein. (EUROIMMUN, Mountain Lakes, New Jersey and Roche Diagnostics, Indianapolis, IN). Modified-Poisson regression models were used to calculate prevalence rate ratios (PRR) and 95% confidence intervals (CI) to identify sociodemographic and clinical risk factors. RESULTS: PROMOTE samples from 918 mothers and 1237 children were analysed. Overall, maternal SARS-CoV-2 seropositivity was 60.1% (95% CI: 56.9 -63.3) and 41.5% (95%CI: 38.8 - 44.2) for children. Non-breastfeeding mothers had a 31% higher risk of SARS-CoV-2 seropositivity compared to breastfeeding mothers (aPRR=1.31, 95%CI: 1.08-1.59). WLHIV with undetectable viral load had a 10% increased risk of SARS-CoV-2 seropositivity (aPRR=1.10, 95%CI: 0.89-1.37). Moreover, those who were normotensive had 12% increased risk SARS-CoV-2 seropositivity (aPRR= 1.12, 95% CI: 0.68-1.85) compared to women with hypertension. Children between 2 and 5 years had a 19% reduced risk of SARS-CoV-2 seropositivity (aPRR=0.81, 95%CI: 0.64-1.02) when compared to younger children. Mother/infant SARS-CoV-2 serostatuses were discordant in 346/802 (43.1%) families tested: mothers+/children- in 72.3%; mothers-/children+ in 26.3%; child+/sibling+ concordance was 34.6%. CONCLUSIONS: These SARS-CoV-2 seropositivity data indicate that by late 2021, about 60% of mothers and about 40% of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. More mothers than their infants tested SARS-CoV-2+, likely due to a greater external exposure for mothers linked to daily routines/employment, and school closures. Breastfeeding was protective for mothers, likely because of higher likelihood of staying home with young children, and thus less exposure. Discordant results between children within the same families underscores the need to further understand transmission dynamics within households.
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Anticuerpos Antivirales , COVID-19 , Infecciones por VIH , SARS-CoV-2 , Humanos , Femenino , COVID-19/epidemiología , COVID-19/inmunología , Lactante , SARS-CoV-2/inmunología , Adulto , Infecciones por VIH/epidemiología , Anticuerpos Antivirales/sangre , Estudios Retrospectivos , Inmunoglobulina G/sangre , Adulto Joven , Masculino , Estudios Seroepidemiológicos , Factores de Riesgo , Recién Nacido , Uganda/epidemiologíaRESUMEN
BACKGROUND: We aimed to assess if maternal human immunodeficiency virus (HIV) drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. METHODS: This was a case-control study of PROMISE study participants. "Cases" were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and "controls" were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers' and their infants' plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including antiretroviral therapy (ART) initiation and last study visits. RESULTS: Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero/peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. CONCLUSIONS: Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone.
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Fármacos Anti-VIH , Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Fármacos Anti-VIH/uso terapéutico , Lactancia Materna , Estudios de Casos y Controles , Resistencia a Medicamentos , Femenino , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Nevirapina/uso terapéutico , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , ARN/uso terapéuticoRESUMEN
BACKGROUND: Tenofovir disoproxil fumarate (TDF) in combination with other antiretroviral (ARV) drugs has been in clinical use for HIV treatment since its approval in 2001. Although the effectiveness of TDF in preventing perinatal HIV infection is well established, information about renal safety during pregnancy is still limited. TRIAL DESIGN: The IMPAACT PROMISE study was an open-label, strategy trial that randomized pregnant women to one of three arms: TDF based antiretroviral therapy (ART), zidovudine (ZDV) based ART, and ZDV alone (standard of care at start of enrollment). The P1084s substudy was a nested, comparative study of renal outcomes in women and their infants. METHODS: PROMISE participants (n = 3543) were assessed for renal dysfunction using calculated creatinine clearance (CrCl) at study entry (> 14 weeks gestation), delivery, and postpartum weeks 6, 26, and 74. Of these women, 479 were enrolled in the P1084s substudy that also assessed maternal calcium and phosphate as well as infant calculated CrCl, calcium, and phosphate at birth. RESULTS: Among the 1338 women who could be randomized to TDF, less than 1% had a baseline calculated CrCl below 80 mL/min. The mean (standard deviation) maternal calculated CrCl at delivery in the TDF-ART arm [147.0 mL/min (51.4)] was lower than the ZDV-ART [155.0 mL/min (43.3); primary comparison] and the ZDV Alone [158.5 mL/min (45.0)] arms; the mean differences (95% confidence interval) were - 8.0 mL/min (- 14.5, - 1.5) and - 11.5 mL/min (- 18.0, - 4.9), respectively. The TDF-ART arm had lower mean maternal phosphate at delivery compared with the ZDV-ART [- 0.14 mg/dL (- 0.28, - 0.01)] and the ZDV Alone [- 0.17 mg/dL (- 0.31, - 0.02)] arms, and a greater percentage of maternal hypophosphatemia at delivery (4.23%) compared with the ZDV-ART (1.38%) and the ZDV Alone (1.46%) arms. Maternal calcium was similar between arms. In infants, mean calculated CrCl, calcium, and phosphate at birth were similar between arms (all CIs included 0). CONCLUSIONS: Although mean maternal calculated CrCl at Delivery was lower in the TDF-ART arm, the difference between arms is unlikely to be clinically significant. During pregnancy, the TDF-ART regimen had no observed safety concerns for maternal or infant renal function. TRIAL REGISTRATION: NCT01061151 on 10/02/2010 for PROMISE (1077BF). NCT01066858 on 10/02/2010 for P1084s.
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Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/efectos adversos , Calcio , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Lactante , Recién Nacido , Fosfatos/uso terapéutico , Embarazo , Tenofovir/efectos adversos , Zidovudina/uso terapéuticoRESUMEN
INTRODUCTION: Untargeted metabolomics holds significant promise for biomarker detection and development. In resource-limited settings, a dried blood spot (DBS)-based platform would offer significant advantages over plasma-based approaches that require a cold supply chain. OBJECTIVES: The primary goal of this study was to compare the ability of DBS- and plasma-based assays to characterize maternal metabolites. Utility of the two assays was also assessed in the context of a case-control predictive model in pregnant women living with HIV. METHODS: Untargeted metabolomics was performed on archived paired maternal plasma and DBS from n = 79 women enrolled in a large clinical trial. RESULTS: A total of 984 named biochemicals were detected across both plasma and DBS samples, of which 627 (63.7%), 260 (26.4%), and 97 (9.9%) were detected in both plasma and DBS, plasma alone, and DBS alone, respectively. Variation attributable to study individual (R2 = 0.54, p < 0.001) exceeded that of the sample type (R2 = 0.21, p < 0.001), suggesting that both plasma and DBS were capable of differentiating individual metabolomic profiles. Log-transformed metabolite abundances were strongly correlated (mean Spearman rho = 0.51) but showed low agreement (mean intraclass correlation of 0.15). However, following standardization, DBS and plasma metabolite profiles were strongly concordant (mean intraclass correlation of 0.52). Random forests classification models for cases versus controls identified distinct feature sets with comparable performance in plasma and DBS (86.5% versus 91.2% mean accuracy, respectively). CONCLUSION: Maternal plasma and DBS samples yield distinct metabolite profiles highly predictive of the individual subject. In our case study, classification models showed similar performance albeit with distinct feature sets. Appropriate normalization and standardization methods are critical to leverage data from both sample types. Ultimately, the choice of sample type will likely depend on the compounds of interest as well as logistical demands.
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Pruebas con Sangre Seca , Manejo de Especímenes , Biomarcadores , Estudios de Casos y Controles , Femenino , Humanos , Metabolómica , EmbarazoRESUMEN
BACKGROUND: High rates of adverse pregnancy outcomes globally raise the need to understand risk factors and develop preventative interventions. The Pregnancy Outcomes in the Era of Universal Antiretroviral Treatment in Sub-Saharan Africa (POISE Study) was a prospective, observational cohort study conducted from 2016 to 2017 in Blantyre, Malawi. We examine the associations between indicators of nutritional status, specifically mid-thigh circumference (MTC) and body-mass index (BMI), and adverse pregnancy outcomes, low birth weight (LBW), preterm birth (PTB), and small-for-gestational age (SGA), in a cohort of HIV-infected and HIV-uninfected women. METHODS: Sociodemographic, clinical, laboratory, and maternal height, weight and MTC data were collected immediately before or after delivery at the Queen Elizabeth Central Hospital (QEHC) and 4 affiliated health centers in Blantyre, Malawi. LBW was defined as birth weight < 2.5 kg; PTB as gestational age < 37 weeks using Ballard score; and SGA as birth weight < 10th percentile for gestational age. Descriptive, stratified, and multivariable logistic regression were conducted using R. RESULTS: Data from 1298 women were analyzed: 614 HIV-infected and 684 HIV-uninfected. MTC was inversely associated with LBW (adjusted odds ratio [aOR] = 0.95, p = 0.03) and PTB (aOR 0.92, p < 0.001), after controlling for HIV status, age, socioeconomic status and hemoglobin. The association between MTC and SGA was (aOR 0.99, p = 0.53). Similarly, higher BMI was significantly associated with lower odds of PTB (aOR 0.90, p < 0.001), LBW (aOR 0.93, p = 0.05), and SGA (aOR 0.95, p = 0.04). CONCLUSIONS: We observed an inverse relationship between MTC and adverse pregnancy outcomes in Malawi irrespective of HIV infection. MTC performs comparably to BMI; the ease of measuring MTC could make it a practical tool in resource-constrained settings for identification of women at risk of adverse pregnancy outcomes.
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Tamaño Corporal/fisiología , Estado Nutricional/fisiología , Complicaciones del Embarazo/epidemiología , Muslo , Adulto , Femenino , Edad Gestacional , Infecciones por VIH , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Malaui/epidemiología , Masculino , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Muslo/fisiología , Adulto JovenRESUMEN
BACKGROUND: Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. METHODS: We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. RESULTS: The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. CONCLUSIONS: Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Zidovudina/uso terapéutico , Adulto , Negro o Afroamericano , Antirretrovirales/efectos adversos , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Edad Gestacional , Infecciones por VIH/etnología , Infecciones por VIH/transmisión , Humanos , Lactante , Mortalidad Infantil , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Nevirapina/administración & dosificación , Atención Perinatal , Embarazo , Resultado del Embarazo , Tenofovir/uso terapéutico , Adulto Joven , Zidovudina/efectos adversosRESUMEN
BACKGROUND: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection. METHODS: We conducted a phase 3, randomized, double-blind, placebo-controlled trial of a monthly vaginal ring containing dapivirine, a non-nucleoside HIV-1 reverse-transcriptase inhibitor, involving women between the ages of 18 and 45 years in Malawi, South Africa, Uganda, and Zimbabwe. RESULTS: Among the 2629 women who were enrolled, 168 HIV-1 infections occurred: 71 in the dapivirine group and 97 in the placebo group (incidence, 3.3 and 4.5 per 100 person-years, respectively). The incidence of HIV-1 infection in the dapivirine group was lower by 27% (95% confidence interval [CI], 1 to 46; P=0.046) than that in the placebo group. In an analysis that excluded data from two sites that had reduced rates of retention and adherence, the incidence of HIV-1 infection in the dapivirine group was lower by 37% (95% CI, 12 to 56; P=0.007) than that in the placebo group. In a post hoc analysis, higher rates of HIV-1 protection were observed among women over the age of 21 years (56%; 95% CI, 31 to 71; P<0.001) but not among those 21 years of age or younger (-27%; 95% CI, -133 to 31; P=0.45), a difference that was correlated with reduced adherence. The rates of adverse medical events and antiretroviral resistance among women who acquired HIV-1 infection were similar in the two groups. CONCLUSIONS: A monthly vaginal ring containing dapivirine reduced the risk of HIV-1 infection among African women, with increased efficacy in subgroups with evidence of increased adherence. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01617096 .).
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Infecciones por VIH/prevención & control , VIH-1 , Pirimidinas/administración & dosificación , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adolescente , Adulto , África Austral/epidemiología , Factores de Edad , Método Doble Ciego , Farmacorresistencia Viral , Femenino , Infecciones por VIH/epidemiología , Humanos , Incidencia , Persona de Mediana Edad , Cooperación del Paciente , Pirimidinas/efectos adversos , Inhibidores de la Transcriptasa Inversa/efectos adversos , Vagina , Adulto JovenRESUMEN
BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. RESULTS: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).
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Antirretrovirales/uso terapéutico , Transmisión de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/transmisión , VIH-1 , Parejas Sexuales , Adulto , Femenino , Estudios de Seguimiento , Infecciones por VIH/prevención & control , Seropositividad para VIH , VIH-1/genética , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Riesgo , Adulto JovenRESUMEN
OBJECTIVES: Highly active antiretroviral therapy (HAART) provision to eligible HIV-infected pregnant and post-partum women is critical for optimizing maternal health. We assessed the impact of maternal HAART on HIV-free survival of breastfed infants in Malawi. METHODS: The post-exposure prophylaxis of infants-Malawi trial (2004-2009) enrolled mothers/infants during labor or immediately post-partum to evaluate 14-week extended infant antiretroviral prophylaxis for preventing HIV transmission through breastfeeding. Mothers meeting national HAART guidelines were referred for therapy. Child HIV-free survival-survival without HIV infection-was compared by maternal HAART status. RESULTS: Overall, 3022 mother-infant pairs contributed 4214 infant/person-years (PY) at-risk for HIV infection or death, with 532 events (incidence 12.6/100 PY, 95 % confidence interval [CI] 11.6-13.7). During follow-up, 349 mothers were HAART initiated; 581 remained HAART naïve with CD4 cell counts <250 cells/mm(3), and 2092 were never HAART-eligible. By 3 months, 11 % of infants with HAART naïve mothers (CD4 < 250) were infected with HIV or died versus 7 % of infants of HAART-initiated mothers and 4 % of infants of HAART-ineligible mothers. Maternal HAART was associated with a 46 % reduction in infant HIV infection or death as compared to infants with HAART naïve mothers (CD4 < 250) (adjusted hazards ratio 0.54, 95 % CI 0.36-0.81). Among HIV-exposed, uninfected infants, breastfeeding, but not HAART, was significantly associated with decreased child mortality. CONCLUSIONS: HIV infection and mortality are high during the first 3 months post-partum in infants of mothers with advanced HIV, and rapid maternal HAART initiation can significantly improve HIV-related infant outcomes. Clinical Trials Registration This study is registered at http://clinicaltrials.gov/ under trial number NCT00115648.
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Terapia Antirretroviral Altamente Activa , Lactancia Materna , Infecciones por VIH/tratamiento farmacológico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4 , Femenino , Estudios de Seguimiento , Infecciones por VIH/etnología , Infecciones por VIH/mortalidad , Humanos , Lactante , Malaui/epidemiología , Madres/estadística & datos numéricos , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Resultado del Embarazo , Análisis de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Data on prevalence of hepatitis E virus (HEV) in Malawi is limited. We tested blood samples from HIV-uninfected and -infected populations of women and men enrolled in research studies in Malawi during 1989-2008 to determine the seroprevalence of HEV, hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Samples were tested for IgG against HEV, total antibodies against HAV and HCV, and presence of HBV surface antigens. Of 800 samples tested, 16.5% were positive for HEV IgG, 99.6% were positive for HAV antibodies, 7.5% were positive for HBV surface antigen, and 7.1% were positive for HCV antibodies. No clear trends over time were observed in the seroprevalence of HEV, and HIV status was not associated with hepatitis seroprevalence. These preliminary data suggest that the seroprevalence of HEV is high in Malawi; the clinical effects may be unrecognized or routinely misclassified.
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Hepatitis E/epidemiología , Adolescente , Adulto , Anciano , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Hepatitis E/inmunología , Hepatitis E/virología , Virus de la Hepatitis E/inmunología , Humanos , Malaui/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).
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Antirretrovirales/uso terapéutico , Transmisión de Enfermedad Infecciosa/prevención & control , Infecciones por VIH/prevención & control , VIH-1 , Adolescente , Adulto , Antirretrovirales/efectos adversos , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Seropositividad para VIH , Humanos , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Parejas Sexuales , Esposos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The vaginal microbiota may play a role in mediating susceptibility to sexually transmitted infections, including Trichomonas vaginalis (TV). METHODS: Data were analyzed from HIV-1-seronegative women participating in HIV Prevention Trials Network Protocol 035. At quarterly visits for up to 30 months, participants completed structured interviews and specimens were collected for genital tract infection testing. T. vaginalis was detected by saline microscopy. Bacterial vaginosis (BV) was characterized by Gram stain using the Nugent score (BV = 7-10; intermediate = 4-6; normal = 0-3 [reference group]). Cox proportional hazards models stratified by study site were used to assess the association between Nugent score category at the prior quarterly visit and TV acquisition. RESULTS: In this secondary analysis, 2920 participants from Malawi, South Africa, United States, Zambia, and Zimbabwe contributed 16,259 follow-up visits. Bacterial vaginosis was detected at 5680 (35%) visits, and TV was detected at 400 (2.5%) visits. Adjusting for age, marital status, hormonal contraceptive use, unprotected sex in the last week and TV at baseline, intermediate Nugent score, and BV at the prior visit were associated with an increased risk of TV (intermediate score: adjusted hazard ratio [aHR], 1.73; 95% confidence interval [CI], 1.21-2.19; BV: aHR, 2.40; 95% CI, 1.92-3.00). Sensitivity analyses excluding 211 participants with TV at baseline were similar to those from the full study population (intermediate score: aHR, 1.54; 95% CI, 1.10-2.14; BV: aHR, 2.23; 95% CI, 1.75-2.84). CONCLUSIONS: Women with a Nugent score higher than 3 were at an increased risk for acquiring TV. If this relationship is causal, interventions that improve the vaginal microbiota could contribute to reductions in TV incidence.
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Seronegatividad para VIH/inmunología , Vaginitis por Trichomonas/microbiología , Trichomonas vaginalis/aislamiento & purificación , Vagina/microbiología , Vaginosis Bacteriana/microbiología , Adulto , África/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Medición de Riesgo , Vaginitis por Trichomonas/epidemiología , Vaginitis por Trichomonas/inmunología , Estados Unidos/epidemiología , Frotis Vaginal , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/inmunologíaRESUMEN
PURPOSE: Gender inequity and adverse health outcomes continue to be of concern among women in sub-Saharan Africa. We determined prevalence of intimate partner violence and excess fertility (having more children than desired) in reproductive age women in Malawi. We also explored factors associated with these outcomes and with spousal fertility intentions. PATIENTS AND METHODS: In a cross-sectional study, a total of 360 women and 410 men were recruited using multi-stage sampling from communities in a peri-urban setting in Blantyre District, Southern Malawi in 2021. Women and men were separately interviewed by trained study workers using a structured questionnaire. In addition to descriptive analyses, we used univariate and multivariate logistic regression models to assess associations of risk factors with the outcomes of intimate partner violence and excess fertility. RESULTS: Among women, lifetime prevalence of intimate partner violence was 23.1%, and excess fertility was experienced by 25.6%. Intimate partner violence was associated with male partners alcohol consumption (adjusted odds ratio 2.13; P = 0.019). Women were more likely to report excess fertility if they were older (adjusted odds ratio 2.0, P<0.001, for a 5-year increase). Alcohol consumption by the male partner (adjusted odds ratio 2.14; P = 0.025) and women being able to refuse sex with their male partner (adjusted odds ratio 0.50; P = 0.036) were associated with discordant fertility preferences. CONCLUSIONS: Intimate partner violence, excess fertility, and social and health inequities continue to be prevalent in Malawi. These data suggest the underlying proximal and distal factors associated with these adverse outcomes such as alcohol consumption may be addressed through education, couple interactive communication, and community dialogue. To ensure sustainability and effectiveness, strong leadership involvement, both governmental and non-governmental, is needed.
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Violencia de Pareja , Niño , Humanos , Masculino , Femenino , Estudios Transversales , Malaui/epidemiología , Factores de Riesgo , Encuestas y Cuestionarios , Fertilidad , Prevalencia , Parejas SexualesRESUMEN
OBJECTIVE: HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD. DESIGN/METHODS: A nested 1â:â1 case-control study ( N â=â362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37âweeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13-23âweeks of gestational age and 4âweeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD. RESULTS: Persistently high interleukin-6 was associated with increased PTD. Compared with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher ( P â<â0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers. CONCLUSION: Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.
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Infecciones por VIH , Inflamación , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Adulto , Inflamación/sangre , Estudios de Casos y Controles , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/sangre , Fármacos Anti-VIH/uso terapéutico , Biomarcadores/sangre , Zidovudina/uso terapéutico , Zidovudina/administración & dosificación , Tenofovir/uso terapéutico , Terapia Antirretroviral Altamente Activa , Lopinavir/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: Lifelong antiretroviral treatment (ART) use is recommended for pregnant and breastfeeding (BF) women living with HIV (WLWH) to prevent perinatal HIV transmission and improve maternal health. We address 2 objectives in this analysis: (1) determine timing and factors associated with BF cessation and (2) assess the impact of BF on health of WLWH on ART. SETTING: This multicountry study included 8 sites in Uganda, Malawi, Zimbabwe, and South Africa. METHODS: This was a prospective study of WLWH on lifelong ART. These women initially participated from 2011 to 2016 in a randomized clinical trial (PROMISE) to prevent perinatal HIV transmission and subsequently reenrolled in an observational study (PROMOTE, 2016-2021) to assess ART adherence, safety, and impact. RESULTS: The PROMOTE cohort included 1987 women on ART. Of them, 752 breastfed and were included in analyses of objective 1; all women were included in analyses of objective 2. The median time to BF cessation varied by country (11.2-19.7 months). Country of residence, age, and health status of women were significantly associated with time to BF cessation (compared with Zimbabwe: Malawi, adjusted hazard ratio [aHR] 0.50, 95% confidence interval [95% CI]: 0.40 to 0.62, P < 0.001; South Africa, aHR 1.49, 95% CI: 1.11 to 2.00, P = 0.008; and Uganda, aHR 1.77, 95% CI: 1.37 to 2.29, P < 0.001). Women who breastfed had lower risk of being "unwell" compared with women who never breastfed (adjusted rate ratio 0.87, 95% CI: 0.81 to 0.95 P = 0.030). CONCLUSION: Women on lifelong ART should be encouraged to continue BF with no concern for their health. Time to BF cessation should be monitored for proper counseling in each country.
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Lactancia Materna , Infecciones por VIH , Embarazo , Femenino , Humanos , Lactancia Materna/psicología , Estudios Prospectivos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Antirretrovirales/uso terapéutico , África Austral , Transmisión Vertical de Enfermedad Infecciosa/prevención & controlRESUMEN
BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37âweeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34âweeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24âmonths (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.
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Lactancia Materna , Infecciones por VIH , Nacimiento Prematuro , Humanos , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Embarazo , Nacimiento Prematuro/epidemiología , Recién Nacido , Lactante , Adulto , India/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Masculino , África/epidemiología , Fármacos Anti-VIH/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission. METHODS: Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. RESULTS: The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P < .001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P < .001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P < .001). CONCLUSIONS: Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection.
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Fármacos Anti-VIH/administración & dosificación , Profilaxis Antibiótica/métodos , Infecciones por VIH/prevención & control , VIH-1/aislamiento & purificación , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Leche Humana/virología , Nevirapina/administración & dosificación , Lactancia Materna/estadística & datos numéricos , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Estimación de Kaplan-Meier , Masculino , Factores de RiesgoRESUMEN
Staphylococcus aureus is a major human-associated pathogen that causes a wide range of clinical infections. However, the increased human dynamics and the changing epidemiology of the species have made it imperative to understand the population structure of local ecotypes, their transmission dynamics, and the emergence of new strains. Since the previous methicillin-resistant S. aureus (MRSA) pandemic, there has been a steady increase in global healthcare-associated infections involving cutaneous and soft tissue and resulting in high morbidities and mortalities. Limited data and paucity of high-quality evidence exist for many key clinical questions about the pattern of S. aureus infections. Using clinical, molecular, and epidemiological characterizations of isolates, hospital data on age and infection sites, as well as antibiograms, we have investigated profiles of circulating S. aureus types and infection patterns. We showed that age-specific profiling in both intensive care unit (ICU) and non-ICU revealed highest infection rates (94.7%) in senior-patients > 50 years; most of which were MRSA (81.99%). However, specific distributions of geriatric MRSA and MSSA rates were 46.5% and 4.6% in ICU and 35.48% and 8.065% in non-ICU, respectively. Intriguingly, the age groups 0−20 years showed uniquely similar MRSA patterns in ICU and non-ICU patients (13.9% and 9.7%, respectively) and MSSA in ICU (11.6%). The similar frequencies of both lineages in youth at both settings is consistent with their increased socializations and gathering strongly implying carriage and potential evolutionary replacement of MSSA by MRSA. However, in age groups 20−50 years, MRSA was two-fold higher in non-ICU (35%) than ICU (18.6%). Interestingly, a highly significant association was found between infection-site and age-groups (p-value 0.000). Skin infections remained higher in all ages; pediatrics 32.14%, adults 56%, and seniors 25% while respiratory infections were lower in pediatrics (14.3%) and adults (17%) while it was highest in seniors (38%). Blood and "other" sites in pediatrics were recorded (28.6%; 25%, respectively), and were slightly lower in adults (18.6%; 8.6%) and seniors (14%; 22.8%), respectively. Furthermore, a significant association existed between infection-site and MRSA (Chi-Square Test, p-value 0.002). Thus, the common cutaneous infections across all age-groups imply that skin is a significant reservoir for endogenous infections; particularly, for geriatrics MRSA. These findings have important clinical implications and in understanding S. aureus profiles and transmission dynamics across different age groups that is necessary for strategic planning in patient management and infection control.
RESUMEN
INTRODUCTION: Optimal adherence to antiretroviral therapy (ART) is crucial to promoting maternal-infant health. SETTING: Fourteen sites in 7 countries within sub-Saharan Africa and India. METHODS: The multicomponent, open-label strategy PROMISE trial enrolled breastfeeding mother-infant pairs not meeting in-country criteria for maternal ART (mART) initiation in the postpartum component within 5 days of delivery. Randomization was to mART versus infant NVP (iNVP) prophylaxis. Infants in the mART arm also received 6 weeks of iNVP. Self-reported adherence was assessed in a secondary analysis. Time-to-event analyses were performed to explore the association between adherence and maternal viral load (mVL) in the mART arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled between 2011 and 2014; the baseline maternal median CD4 was 686 (IQR 553-869), and the median mVL was 322 copies/mL (IQR 40-1422). Self-reported adherence was lower in the mART arm compared with the iNVP arm (no missed doses within 4 weeks of all study visits: 66% vs 83%; within 2 weeks: 71% vs 85%; P < 0.0001). The iNVP adherence at week 6 was high in both arms: 97% in mART arm; 95% in iNVP arm. Time-to-event analyses showed that adherence to mART was associated with time to first mVL ≥400 copies/mL ( P < 0.0001). Missing 1 full day of doses over 3 days was associated with a 66% risk of mVL ≥1000 copies/mL (HR: 1.66; 95% CI: 1.37, 1.99). CONCLUSIONS: Postpartum women were less adherent to their own ART than mothers providing their infant's nevirapine prophylaxis. The self-reported missed mART doses were associated with high mVL. Strategies to optimize postpartum mART adherence are urgently needed. CLINICAL TRIAL NUMBER: ClinicalTrials.gov: NCT01061151; closed to follow-up.