RESUMO
We evaluated effects of antiretroviral (ARV) therapy and lipid-based nutrient supplements (LNSs) on iron, copper, and zinc in milk of exclusively breastfeeding HIV-infected Malawian mothers and their correlations with maternal and infant biomarkers. Human milk and blood at 2, 6, and 24 weeks post-partum and blood during pregnancy (≤30 weeks gestation) were collected from 535 mothers/infant-pairs in the Breastfeeding, Antiretrovirals, and Nutrition study. The participants received ARV, LNS, ARV and LNS, or no intervention from 0 to 28 weeks post-partum. ARVs negatively affected copper and zinc milk concentrations, but only at 2 weeks, whereas LNS had no effect. Among all treatment groups, approximately 80-90% of copper and zinc and <50% of iron concentrations met the current adequate intake for infants at 2 weeks and only 1-19% at 24 weeks. Pregnancy haemoglobin was negatively correlated with milk iron at 2 and 6 weeks (r = -.18, p < .02 for both). The associations of the milk minerals with each other were the strongest correlations observed (r = .11-.47, p < .05 for all); none were found with infant biomarkers. At 2 weeks, moderately anaemic women produced milk higher in iron when ferritin was higher or TfR lower. At 6 weeks, higher maternal α-1-acid glycoprotein and C-reactive protein were associated with higher milk minerals in mildly anaemic women. Infant TfR was lower when milk mineral concentrations were higher at 6 weeks and when mothers were moderately anaemic during pregnancy. ARV affects copper and zinc milk concentrations in early lactation, and maternal haemoglobin during pregnancy and lactation could influence the association between milk minerals and maternal and infant iron status and biomarkers of inflammation.
Assuntos
Fármacos Anti-HIV/farmacologia , Cobre/metabolismo , Infecções por HIV/tratamento farmacológico , Ferro/metabolismo , Lipídeos/farmacologia , Leite Humano/efeitos dos fármacos , Zinco/metabolismo , Adulto , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/sangue , Aleitamento Materno , Suplementos Nutricionais , Feminino , Hemoglobinas/metabolismo , Humanos , Lactente , Recém-Nascido , Inflamação/sangue , Ferro/sangue , Lipídeos/administração & dosagem , Malaui , Masculino , Leite Humano/metabolismo , Mães , Adulto JovemRESUMO
BACKGROUND: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings. OBJECTIVE: We examined associations of highly active antiretroviral therapy (HAART) and lipid-based nutrient supplements (LNS) with concentrations of selected micronutrients in HIV-infected Malawian women at 24 wk postpartum. METHODS: Plasma micronutrient concentrations were measured in a subsample (n = 690) of Breastfeeding, Antiretrovirals, and Nutrition (BAN) study participants who were randomly assigned at delivery to receive HAART, LNS, HAART+LNS, or no HAART/no LNS (control). HAART consisted of protease inhibitor-based triple therapy. LNS (140 g/d) met energy and micronutrient requirements of lactation. Multivariable linear regression tested the association of HAART and LNS, plus their interaction, with micronutrient concentrations, controlling for season, baseline viral load, and baseline CD4 count. RESULTS: We found significant HAART by LNS interactions for folate (P = 0.051), vitamin B-12 (P < 0.001), and transferrin receptors (TfRs) (P = 0.085). HAART was associated with lower folate (with LNS: -27%, P < 0.001; without LNS: -12%, P = 0.040) and higher TfR concentrations (with LNS: +14%, P = 0.004; without LNS: +28%, P < 0.001), indicating iron deficiency. LNS increased folate (with HAART: +17%, P = 0.037; without HAART: +39%, P < 0.001) and decreased TfR concentrations (with HAART only: -12%, P = 0.023). HAART was associated with lower vitamin B-12 concentrations only when LNS was present (-18%, P = 0.001), whereas LNS increased vitamin B-12 only when no HAART was present (+27%, P < 0.001). HAART, but not LNS, was associated with higher retinol-binding protein (RBP; +10%, P = 0.007). We detected no association of HAART or LNS with selenium, ferritin, or hemoglobin. CONCLUSION: The association of HAART with lower folate, iron deficiency, and higher RBP plus the attenuation of LNS effects on folate and vitamin B-12 when combined with HAART has implications for the health of lactating HIV-infected women taking HAART in prevention of mother-to-child transmission programs. This trial was registered at clinicaltrials.gov as NCT00164736.
Assuntos
Antirretrovirais/uso terapêutico , Suplementos Nutricionais , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Lipídeos/química , Micronutrientes/sangue , Adulto , Antirretrovirais/administração & dosagem , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/epidemiologia , Humanos , Malaui/epidemiologia , Masculino , Adulto JovemRESUMO
BACKGROUND: We established Safeguard the Family (STF) to support Ministry of Health (MoH) scale-up of universal antiretroviral therapy (ART) for HIV-infected pregnant and breastfeeding women (Option B+) and to strengthen the prevention of mother-to-child transmission (PMTCT) cascade from HIV testing and counseling (HTC) through maternal ART provision and post-delivery early infant HIV diagnosis (EID). To these ends, we implemented the following interventions in 5 districts: 1) health worker training and mentorship; 2) couples' HTC and male partner involvement; 3) women's psychosocial support groups; and 4) health and laboratory system strengthening for EID. METHODS: We conducted a serial cross-sectional study using facility-level quarterly (Q) program data and individual-level infant HIV-1 DNA PCR data to evaluate STF performance on PMTCT indicators for project years (Y) 1 (April-December 2011) through 3 (January-December 2013), and compared these results to national averages. RESULTS: Facility-level uptake of HTC, ART, infant nevirapine prophylaxis, and infant DNA PCR testing increased significantly from quarterly baselines of 66 % (n/N = 32,433/48,804), 23 % (n/N = 442/1,958), 1 % (n/N = 10/1,958), and 52 % (n/N = 1,385/2,644) to 87 % (n/N = 39,458/45,324), 96 % (n/N = 2,046/2,121), 100 % (n/N = 2,121/2,121), and 62 % (n/N = 1,462/2,340), respectively, by project end (all p < 0.001). Quarterly HTC, ART, and infant nevirapine prophylaxis uptake outperformed national averages over years 2-3. While transitioning EID laboratory services to MoH, STF provided first-time HIV-1 DNA PCR testing for 2,226 of 11,261 HIV-exposed infants (20 %) tested in the MoH EID program in STF districts from program inception (Y2) through Y3. Of these, 78 (3.5 %) tested HIV-positive. Among infants with complete documentation (n = 608), median age at first testing decreased from 112 days (interquartile range, IQR: 57-198) in Y2 to 76 days (IQR: 46-152) in Y3 (p < 0.001). During Y3 (only year with national data for comparison), non-significantly fewer exposed infants tested HIV-positive (3.6 %) at first testing in STF districts than nationally (4.1 %) (p = 0.4). CONCLUSIONS: STF interventions, integrated within the MoH Option B+ program, achieved favorable HTC, maternal ART, infant prophylaxis, and EID services uptake, and a low proportion of infants found HIV-infected at first DNA PCR testing. Continued investments are needed to strengthen the PMTCT cascade, particularly around EID.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Aleitamento Materno , Estudos Transversais , Diagnóstico Precoce , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Malaui , Masculino , Profilaxia Pós-Exposição , Período Pós-Parto , Gravidez , Cuidado Pré-Natal , Avaliação de Programas e Projetos de Saúde , Adulto JovemRESUMO
Infant iron status at birth is influenced by maternal iron status during pregnancy; however, there are limited data on the extent to which maternal iron status is associated with infant iron status during exclusive breastfeeding. We evaluated how maternal and infant hemoglobin and iron status [soluble transferrin receptors (TfR) and ferritin] were related during exclusive breastfeeding in HIV-infected women and their infants. The Breastfeeding, Antiretrovirals, and Nutrition Study was a randomized controlled trial in Lilongwe, Malawi, in which HIV-infected women were assigned with a 2 × 3 factorial design to a lipid-based nutrient supplement (LNS), or no LNS, and maternal, infant, or no antiretroviral drug, and followed for 24 wk. Longitudinal models were used to relate postpartum maternal hemoglobin (n = 1926) to concurrently measured infant hemoglobin, adjusting for initial infant hemoglobin values. In a subsample, change in infant iron status (hemoglobin, log ferritin, log TfR) between 2 (n = 352) or 6 wk (n = 167) and 24 wk (n = 519) was regressed on corresponding change in the maternal indicator, adjusting for 2 or 6 wk values. A 1 g/L higher maternal hemoglobin at 12, 18, and 24 wk was associated with a 0.06 g/L (P = 0.01), 0.10 g/L (P < 0.001), and 0.06 g/L (P = 0.01), respectively, higher infant hemoglobin. In the subsample, a reduction in maternal log TfR and an increase in hemoglobin from initial measurement to 24 wk were associated with the same pattern in infant values (log TfR ß = -0.18 mg/L, P < 0.001; hemoglobin ß = 0.13 g/L, P = 0.01). Given the observed influence of maternal and initial infant values, optimizing maternal iron status in pregnancy and postpartum is important to protect infant iron status. This trial was registered at clinicaltrials.gov as NCT00164736.
Assuntos
Aleitamento Materno , Suplementos Nutricionais , Hemoglobinas/metabolismo , Ferro da Dieta/administração & dosagem , Ferro da Dieta/sangue , Receptores da Transferrina/sangue , Adulto , Antirretrovirais/administração & dosagem , Biomarcadores/sangue , Feminino , Ferritinas/sangue , Infecções por HIV , Humanos , Lactente , Modelos Lineares , Estudos Longitudinais , Malaui/epidemiologia , Masculino , Mães , Estado Nutricional , Período Pós-Parto/fisiologia , Gravidez , Adulto JovemRESUMO
OBJECTIVE: To determine, for the WHO algorithm for point-of-care diagnosis of HIV infection, the agreement levels between paediatricians and non-physician clinicians, and to compare sensitivity and specificity profiles of the WHO algorithm and different CD4 thresholds against HIV PCR testing in hospitalised Malawian infants. METHODS: In 2011, hospitalised HIV-exposed infants <12 months in Lilongwe, Malawi, were evaluated independently with the WHO algorithm by both a paediatrician and clinical officer. Blood was collected for CD4 and molecular HIV testing (DNA or RNA PCR). Using molecular testing as the reference, sensitivity, specificity and positive predictive value (PPV) were determined for the WHO algorithm and CD4 count thresholds of 1500 and 2000 cells/mm(3) by paediatricians and clinical officers. RESULTS: We enrolled 166 infants (50% female, 34% <2 months, 37% HIV infected). Sensitivity was higher using CD4 thresholds (<1500, 80%; <2000, 95%) than with the algorithm (physicians, 57%; clinical officers, 71%). Specificity was comparable for CD4 thresholds (<1500, 68%, <2000, 50%) and the algorithm (paediatricians, 55%, clinical officers, 50%). The positive predictive values were slightly better using CD4 thresholds (<1500, 59%, <2000, 52%) than the algorithm (paediatricians, 43%, clinical officers 45%) at this prevalence. CONCLUSION: Performance by the WHO algorithm and CD4 thresholds resulted in many misclassifications. Point-of-care CD4 thresholds of <1500 cells/mm(3) or <2000 cells/mm(3) could identify more HIV-infected infants with fewer false positives than the algorithm. However, a point-of-care option with better performance characteristics is needed for accurate, timely HIV diagnosis.
Assuntos
Algoritmos , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/diagnóstico , Hospitalização , Transmissão Vertical de Doenças Infecciosas , Feminino , Pessoal de Saúde , Humanos , Lactente , Malaui , Masculino , Sistemas Automatizados de Assistência Junto ao Leito , Valores de Referência , Sensibilidade e Especificidade , Organização Mundial da SaúdeRESUMO
BACKGROUND: South Africa has 6.4 million adults over the age of 15 living with HIV. Gender inequality issues continue to drive the HIV epidemic in South Africa, where Black African women bear the greatest HIV burden. Limited access to services; little capacity to negotiate sex and condom use; and other legal, social, and economic inequities make women highly vulnerable to HIV infection. Behavioral interventions have been shown to decrease risk behaviors, but they have been less successful in reducing HIV incidence. Conversely, biomedical prevention strategies have proven to be successful in reducing HIV incidence, but require behavioral interventions to increase uptake and adherence. Consequently, there is a need for integrated approaches that combine biomedical and behavioral interventions. Effective combination prevention efforts should comprise biomedical, behavioral, and structural programming proven in randomized trials that focuses on the driving forces and key populations at higher risk of HIV infection and transmission. METHODS/DESIGN: This prospective, geographically clustered randomized field experiment is enrolling participants into two arms: a control arm that receives standard HIV testing and referral for treatment; and an intervention arm that receives an evidence-based, woman-focused behavioral intervention that emphasizes risk reduction and retention, the Women's Health CoOp. We divided the city of Pretoria into 14 mutually exclusive geographic zones and randomized these zones into either the control arm or the intervention arm. Outreach workers are recruiting drug-using women from each zone. At baseline, eligible participants complete a questionnaire and biological testing for HIV, recent drug use, and pregnancy. Follow-up interviews are completed at 6 and 12 months. DISCUSSION: The biobehavioral intervention in this study merges an efficacious behavioral HIV prevention intervention for women with biomedical prevention through HIV treatment as prevention using a Seek, Test, Treat and Retain strategy. This combination biobehavioral intervention is designed to (1) improve the quality of life and reduce HIV infectiousness among women who are HIV positive, and (2) reduce HIV risk behaviors among women regardless of their HIV status. If efficacious, this intervention could help control the HIV epidemic in South Africa. TRIAL REGISTRATION: Trial registration no: NCT01497405.
Assuntos
População Negra , Infecções por HIV/prevenção & controle , Comportamento de Redução do Risco , Transtornos Relacionados ao Uso de Substâncias , Populações Vulneráveis , Saúde da Mulher , Adolescente , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , Humanos , Incidência , Programas de Rastreamento , Gravidez , Estudos Prospectivos , Qualidade de Vida , Assunção de Riscos , Sexo Seguro , África do Sul , Adulto JovemRESUMO
BACKGROUND: We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. METHODS: We randomly assigned 2369 HIV-1-positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth. Rates were compared with the use of the log-rank test. RESULTS: Among mother-infant pairs, 5.0% of infants were HIV-1-positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. CONCLUSIONS: The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)
Assuntos
Antirretrovirais/uso terapêutico , Aleitamento Materno , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Adulto , Antirretrovirais/efeitos adversos , Contagem de Linfócito CD4 , Hipersensibilidade a Drogas/etiologia , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Soronegatividade para HIV , Humanos , Recém-Nascido , Estimativa de Kaplan-Meier , Lamivudina/uso terapêutico , Masculino , Neutropenia/induzido quimicamente , Nevirapina/efeitos adversos , Nevirapina/uso terapêutico , Gravidez , Fatores de Risco , Síndrome de Stevens-Johnson/induzido quimicamente , Adulto Jovem , Zidovudina/uso terapêuticoRESUMO
The Breastfeeding, Antiretrovirals, and Nutrition (BAN) Study randomized HIV-infected mothers and their infants to receive either maternal lipid-based nutrient supplements (LNS) during lactation or no LNS and then to 1 of 3 antiretroviral drug (ARV) arms (maternal, infant, or no drugs). Assigned interventions were provided from 0 to 28 wk and all infants (n = 1619) were given LNS during (24-28 wk) and following (28-48 wk) weaning. This paper assesses the feasibility of infant LNS as a breastmilk replacement and uses longitudinal random effects models to examine associations of interventions, morbidity, and season with weight-for-age (WAZ), length-for-age (LAZ), and BMI-for-age (BMIZ) Z-scores from 24 to 48 wk. Infant LNS adherence was high (94.1% ate it daily). From 24 to 48 wk, mean WAZ (-0.42 to -0.76 SD; P < 0.001) and LAZ (-0.93 to -1.56 SD; P < 0.001) steadily declined, whereas BMIZ remained >0 throughout. A higher LAZ was associated with assignment to the maternal LNS arm (ß=0.19; P < 0.05). Lower WAZ and BMIZ were associated with seasonal food insecurity (ß=-0.08 and -0.09, respectively; both P < 0.001), fever (ß=-0.07 and -0.13; both P < 0.001), diarrhea (ß=-0.19 and -0.23; both P < 0.001), and assignment to the infant ARV arm (ß=-0.17 and -0.17; both P < 0.05). The magnitude of the season and morbidity effects was small and BAN infants had higher weights and lengths than their counterparts in the general population. High LNS adherence and the modest impact of morbidity on growth indicate that LNS is a feasible breastmilk replacement for HIV-exposed infants weaned early, but controlled trials are needed to quantify the effects of LNS on growth in this population.
Assuntos
Comorbidade , Dieta , Suplementos Nutricionais , Crescimento , Infecções por HIV/dietoterapia , Fenômenos Fisiológicos da Nutrição do Lactente , Cooperação do Paciente , Adulto , Estatura , Índice de Massa Corporal , Peso Corporal , Alimentação com Mamadeira , Diarreia/complicações , Estudos de Avaliação como Assunto , Feminino , Febre/complicações , Abastecimento de Alimentos , Transtornos do Crescimento/prevenção & controle , Infecções por HIV/complicações , Humanos , Lactente , Fórmulas Infantis , Transmissão Vertical de Doenças Infecciosas , Estudos Longitudinais , Masculino , Desnutrição/complicações , Desnutrição/prevenção & controle , Leite Humano , Gravidez , Complicações Infecciosas na Gravidez , Estações do Ano , Desmame , Adulto JovemRESUMO
Maternal weight loss during exclusive breastfeeding may influence the growth of exclusively breast-fed infants through impaired quality or quantity of breast milk. This study evaluated how maternal weight loss from 2 to 24 wk postpartum was related to infant weight and length gain in 1309 lactating HIV-infected mothers and their exclusively breast-fed infants. Malawian mother-infant pairs in the Breastfeeding, Antiretrovirals, and Nutrition Study were randomized with a 2 × 3 factorial design to a 2-arm nutritional intervention with a lipid-based nutrient supplement (LNS), meeting nutritional needs of lactation, or no LNS and a 3-arm antiretroviral (ARV) intervention (maternal, infant, or no ARV regimen). Linear regression models were used to relate maternal weight loss (weight loss vs. no weight loss) to infant weight and length gain from birth to 24 mo, stratifying by gender and controlling for maternal BMI at 2 wk (mean ± SD: 23.2 ± 3.0 kg/m(2)) and interacting maternal BMI with weight loss. In adjusted models, compared with daughters of women who did not lose weight, length and weight gain were lower in daughters whose mothers had a lower BMI at 2 wk postpartum coupled with the weight loss. For example, among mothers with an initial BMI of 18 kg/m(2), daughters of those who lost weight gained less weight [ß = -0.29 kg (95% CI: -0.53, -0.06)] and length [ß = -0.88 cm (95% CI: -1.52, -0.23)] from birth to 24 wk than daughters of those who gained weight. Though effects were only observed in girls, suggesting possible gender differences in suckling and feeding behavior, these findings indicate that maternal weight loss with low energy reserves represents a risk factor for poor infant growth outcomes.
Assuntos
Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Suplementos Nutricionais , Infecções por HIV/fisiopatologia , Fenômenos Fisiológicos da Nutrição Materna , Redução de Peso , Adulto , Antirretrovirais/uso terapêutico , Estatura , Estudos Transversais , Feminino , Infecções por HIV/dietoterapia , Humanos , Lactente , Lactação , Modelos Lineares , Modelos Logísticos , Malaui/epidemiologia , Masculino , Leite Humano , Gravidez , Aumento de Peso , Adulto JovemRESUMO
There are potential health risks associated with the use of early weaning to prevent mother-to-child transmission of human immunodeficiency virus (HIV) in resource-poor settings. Our objective was to examine growth and nutrient inadequacies among a cohort of children weaned early. Children participating in the Breastfeeding Antiretrovirals and Nutrition (BAN) Study in Lilongwe, Malawi, had HIV-infected mothers, were weaned at 6 months and fed LNS until 12 months. 40 HIV-negative, BAN-exited children were compared with 40 HIV-negative, community children matched on age, gender and local health clinic. Nutrient intake was calculated from 24-h dietary recalls collected from BAN-exited children. Anthropometric measurements were collected from BAN-exited and matched community children at 15-16 months, and 2 months later. Longitudinal random effects sex-stratified models were used to evaluate anthropometric differences between the two groups. BAN-exited children consumed adequate energy, protein and carbohydrates but inadequate amounts of fat. The prevalence of inadequate micronutrient intakes were: 46% for vitamin A; 20% for vitamin B6; 69% for folate; 13% for vitamin C; 19% for iron; 23% for zinc. Regarding growth, BAN-exited girls gained weight at a significantly lower rate {0.02 g kg(-1) per day [95% confidence interval (CI): 0.01, 0.03]} than their matched comparison [0.05 g kg(-1) per day (95% CI: 0.03, 0.07)]; BAN girls grew significantly slower [0.73 cm month(-1) (95% CI: 0.40,1.06)] than their matched comparison (1.55 cm month(-1) [95% CI: 0.98, 2.12]). Among this sample of BAN-exited children, early weaning was associated with dietary deficiencies and girls experienced reduced growth velocity. In resource-poor settings, HIV prevention programmes must ensure that breastfeeding stop only once a nutritionally adequate and safe diet without breast milk can be provided.
Assuntos
Dieta , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Desmame , Adulto , Antirretrovirais/administração & dosagem , Ácido Ascórbico/administração & dosagem , Peso Corporal , Aleitamento Materno/métodos , Gorduras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Ingestão de Energia , Feminino , Ácido Fólico/administração & dosagem , Seguimentos , Soronegatividade para HIV , Humanos , Lactente , Ferro da Dieta/administração & dosagem , Estudos Longitudinais , Malaui , Masculino , Desnutrição/epidemiologia , Desnutrição/prevenção & controle , Micronutrientes/administração & dosagem , Estado Nutricional , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Estações do Ano , Fatores Socioeconômicos , Inquéritos e Questionários , Vitamina A/administração & dosagem , Vitamina B 6/administração & dosagem , Vitaminas/administração & dosagem , Adulto Jovem , Zinco/administração & dosagemRESUMO
The Breastfeeding, Antiretrovirals, and Nutrition Study evaluated the effect of daily consumption of lipid-based nutrient supplements (LNS) by 2121 lactating, HIV-infected mothers on the growth of their exclusively breast-fed, HIV-uninfected infants from 0 to 24 wk. The study had a 2 × 3 factorial design. Malawian mothers with CD4(+) ≥250 cells/mm(3), hemoglobin ≥70 g/L, and BMI ≥17 kg/m(2) were randomized within 36 h of delivery to receive either no LNS or 140 g/d of LNS to meet lactation energy and protein needs, and mother-infant pairs were assigned to maternal antiretroviral drugs (ARV), infant ARV, or no ARV. Sex-stratified, longitudinal, random effects models were used to estimate the effect of the 6 study arms on infant weight, length, and BMI. Logistic regression models were used to calculate the odds of growth faltering [decline in weight-for-age Z-score (WAZ) or length-for-age Z-score (LAZ) >0.67] using the control arm as the reference. Although some differences between study arms emerged with increasing infant age in boys, there were no consistent effects of the maternal supplement across the 3 growth outcomes in longitudinal models. At the ages where differences were observed, the effects on weight and BMI were quite small (≤200 g and ≤0.4 kg/m(2)) and unlikely to be of clinical importance. Overall, 21 and 34% of infants faltered in WAZ and LAZ, respectively. Maternal supplementation did not reduce the odds of infant weight or length faltering from 0 to 24 wk in any arm. These results indicate that blanket supplementation of HIV-infected lactating women may have little impact on infant growth.
Assuntos
Aleitamento Materno , Dieta , Suplementos Nutricionais , Transtornos do Crescimento/etiologia , Crescimento/efeitos dos fármacos , Infecções por HIV/complicações , Fenômenos Fisiológicos da Nutrição do Lactente/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/uso terapêutico , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Antígenos CD4 , Gorduras na Dieta/farmacologia , Gorduras na Dieta/uso terapêutico , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/prevenção & controle , Hemoglobinas/metabolismo , Humanos , Lactente , Recém-Nascido , Lactação , Lipídeos/farmacologia , Modelos Logísticos , Estudos Longitudinais , Malaui/epidemiologia , Masculino , Necessidades Nutricionais , Prevalência , Desnutrição Proteico-Calórica/prevenção & controle , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)-associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day, but mortality rates remain unacceptably high. Therefore, we examined the effect of adding oral flucytosine to fluconazole. METHODS: From 13 February through 2 December 2008, HIV-seropositive, antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up. The primary end point was early fungicidal activity, derived from quantitative cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were safety and 2- and 10-week mortality. RESULTS: Forty-one patients were analyzed. Baseline mental status, cryptococcal burden, opening pressure, CD4(+) cell count, and HIV load were similar between groups. Combination therapy was more fungicidal than fluconazole alone (mean early fungicidal activity +/- standard deviation -0.28 +/- 0.17 log colony-forming units [CFU]/mL per day vs -0.11 +/- 0.09 log CFU/mL per day; P < .001). The combination arm had fewer deaths by 2 weeks (10% vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia with combination therapy (5 vs 1, within the first 2 weeks; P = .20), but there was no increase in infection-related adverse events. CONCLUSIONS: The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/uso terapêutico , Fluconazol/uso terapêutico , Flucitosina/uso terapêutico , Meningite Criptocócica/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Administração Oral , Adulto , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Líquido Cefalorraquidiano/microbiologia , Cryptococcus/isolamento & purificação , Quimioterapia Combinada , Feminino , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Flucitosina/administração & dosagem , Flucitosina/efeitos adversos , Infecções por HIV/complicações , Humanos , Malaui , Masculino , Meningite Criptocócica/microbiologia , Meningite Criptocócica/mortalidade , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
A significant number of infants acquire HIV-1 through their infected mother's breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n = 63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n = 42), compared to those that eventually acquired infection (n = 21), did not possess higher nAb responses against heterologous envelopes (P = 0.46) or their mothers' variants (P = 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P = 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P = 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P = 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity.IMPORTANCE Passive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby.
Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1/imunologia , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/imunologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Infecções por HIV/sangue , Infecções por HIV/complicações , Humanos , Imunidade Materno-Adquirida , Lactente , Recém-Nascido , Leite Humano/imunologia , Leite Humano/virologia , Morbidade , Testes de Neutralização , Gravidez , Complicações Infecciosas na Gravidez/virologia , Adulto JovemRESUMO
OBJECTIVE: The objective of this study is to determine whether detection of HIV infection was delayed in infants exposed to antiretroviral prophylaxis to prevent HIV transmission during breastfeeding. DESIGN: The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was a randomized trial of 2369 mother-infant pairs conducted from 2004 to 2010. In addition to an intrapartum regimen, all mother-infant pairs were randomly assigned to three antiretroviral intervention arms during 28 weeks of breastfeeding: no further antiretroviral prophylaxis (control arm); infant-daily nevirapine (nevirapine arm); and maternal zidovudine, lamivudine and either nevirapine, nelfinavir or lopinavir-ritonavir (maternal arm). After breastfeeding cessation counselling and stopping the antiretroviral interventions by 28 weeks, 28 infant HIV infections occurred. METHODS: To determine whether these infections occurred during the breastfeeding and antiretroviral intervention phase but had delayed detection on the antiretroviral arms, we performed ultrasensitive (droplet digital PCR) HIV testing on infants with stored peripheral blood mononuclear cell (PBMC) specimens at 24 weeks (nâ=â9). RESULTS: Of the nine infants, all three on the infant nevirapine arm had detectable HIV DNA at 24 weeks, compared with two of four on the maternal antiretroviral arm and one of two on the control arm. For infants with detectable HIV at 24 weeks, the median delay in detection between the ultrasensitive and standard assays was 18.3 weeks for the nevirapine arm, 15.4 weeks for the maternal arm and 9.4 weeks for the control arm. CONCLUSION: The prolonged inability to detect HIV with standard assays in the context of postnatal antiretroviral prophylaxis suggests that early antiretrovirals may restrict HIV replication sufficiently to lead to missed diagnosis among infected infants. Therefore, repeat virologic testing is warranted beyond the WHO-recommended point of testing at 6 weeks after breastfeeding cessation.
Assuntos
Antirretrovirais/administração & dosagem , Aleitamento Materno , Diagnóstico Tardio , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Testes Diagnósticos de Rotina/métodos , Técnicas de Genotipagem , HIV/classificação , HIV/genética , HIV/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Lactente , Recém-Nascido , Epidemiologia MolecularRESUMO
OBJECTIVE: In resource-limited settings without safe alternatives to breastfeeding, the WHO recommends exclusive breastfeeding and antiretroviral (ARV) prophylaxis. Given the high prevalence of anemia among HIV-infected women, mothers and their infants (through fetal iron accretion) may be at risk of iron deficiency. We assessed the effects of maternal micronutrient-fortified lipid-based nutrient supplements (LNS) and maternal ARV treatment or infant ARV prophylaxis on maternal and infant iron status during exclusive breastfeeding from birth to 24 weeks. METHODS: The Breastfeeding, Antiretrovirals, and Nutrition study was a randomized controlled trial conducted in Lilongwe, Malawi, from 2004 to 2010. HIV-infected mothers (CD4 >200 cells/µL) and their infants were randomly assigned to 28-week interventions: maternal LNS/maternal ARV (n = 424), maternal LNS/infant ARV (n = 426), maternal LNS (n = 334), maternal ARV (n = 425), infant ARV (n = 426), or control (n = 334). Longitudinal models tested intervention effects on hemoglobin (Hb). In a subsample (n = 537) with multiple iron indicators, intervention effects on Hb, transferrin receptors (TfR), and ferritin were tested with linear and Poisson regression. RESULTS: In longitudinal models, LNS effects on maternal and infant Hb were minimal. In subsample mothers, maternal ARVs were associated with tissue iron depletion (TfR >8.3 mg/L) (risk ratio: 3.1, P < 0.01), but not in ARV-treated mothers receiving LNS (P = 0.17). LNS without ARVs was not associated with iron deficiency or anemia (P > 0.1). In subsample infants, interventions were not associated with impaired iron status (all P > 0.1). CONCLUSIONS: Maternal ARV treatment with protease inhibitors is associated with maternal tissue iron depletion; but LNS mitigates adverse effects. ARVs do not seem to influence infant iron status; however, extended use needs to be evaluated.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Aleitamento Materno , Suplementos Nutricionais , Infecções por HIV/complicações , Deficiências de Ferro , Esquema de Medicação , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Hemoglobinas/análise , Humanos , Lactente , Recém-Nascido , Ferro/administração & dosagem , Ferro/uso terapêutico , Ferro da Dieta/administração & dosagem , Ferro da Dieta/farmacologia , Estudos Longitudinais , Malaui/epidemiologia , MasculinoRESUMO
OBJECTIVE: The objective of this study is to assess nevirapine (NVP) resistance in infants who became infected in the three arms of the Breastfeeding, Antiretrovirals and Nutrition (BAN) study: daily infant NVP prophylaxis, triple maternal antiretrovirals or no extra intervention for 28 weeks of breastfeeding. DESIGN: A prospective cohort study. METHODS: The latest available plasma or dried blood spot specimen was tested from infants who became HIV-positive between 3 and 48 weeks of age. Population sequencing was used to detect mutations associated with reverse transcriptase inhibitor resistance. Sequences were obtained from 22 out of 25 transmissions in the infant-NVP arm, 23 out of 30 transmissions in the maternal-antiretroviral arm and 33 out of 38 transmissions in the control arm. RESULTS: HIV-infected infants in the infant-NVP arm were significantly more likely to have NVP resistance than infected infants in the other two arms of the trial, especially during breastfeeding through 28 weeks of age (56% in infant-NVP arm vs. 6% in maternal-antiretroviral arm and 11% in control arm, P»0.004). There was a nonsignificant trend, suggesting that infants with NVP resistance tended to be infected earlier and exposed to NVP while infected for a greater duration than infants without resistance. CONCLUSION: Infants on NVP prophylaxis during breastfeeding are at a reduced risk of acquiring HIV, but are at an increased risk of NVP resistance if they do become infected. These findings point to the need for frequent HIV testing of infants while on NVP prophylaxis, and for the availability of antiretroviral regimens excluding NVP for treating infants who become infected while on such a prophylactic regimen.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Aleitamento Materno , Farmacorresistência Viral , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Nevirapina/administração & dosagem , Fármacos Anti-HIV/farmacologia , Quimioprevenção/métodos , Feminino , Genótipo , HIV-1/genética , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Mutação , Nevirapina/farmacologia , Estudos Prospectivos , RNA Viral/genética , Análise de Sequência de DNARESUMO
Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) because of shared routes of transmission. With the advent of highly active antiretroviral therapy (HAART) regimens capable of controlling HIV replication and dramatically prolonging the survival of HIV-infected patients, the impact of co-morbid infections such as HBV and HCV has come into focus. Several studies have monitored HBV or HCV viral loads following initiation of HAART, with disparate results. The effects of HAART on hepatitis B and C plasma viral loads (n = 9 and 32, respectively) and on liver enzyme levels were studied in a large cohort of prospectively studied subjects with advanced stage HIV disease. Comparing the mean pre- and post-HAART levels, there was an estimated increase of (a) 1.40 log(10) from 4.83 to 6.24 log(10) for HBV plasma viral load (P = 0.07), (b) 0.74 log(10) from 6.38 to 7.12 log(10) for HCV plasma viral load (P = 0.001), and (c) 19.4 U/L from 37.4 to 56.8 U/L for serum alanine aminotransferase (P < 0.001). While the number of subjects co-infected with HIV and HBV was limited, these data collected in a population of advanced stage HIV-infected patients raises questions regarding the interactions of these viruses with each other and the host immune system and has implications regarding the order in which antiviral therapies are initiated.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Adulto , Alanina Transaminase/sangue , DNA Viral/sangue , Feminino , Hepacivirus/crescimento & desenvolvimento , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Fígado/enzimologia , Masculino , Estudos Prospectivos , RNA Viral/sangue , Carga Viral , ViremiaRESUMO
BACKGROUND: Selenium is found in soils and is essential for human antioxidant defense and immune function. In Malawi, low soil selenium and dietary intakes coupled with low plasma selenium concentrations in HIV infection could have negative consequences for the health of HIV-infected mothers and their exclusively breastfed infants. OBJECTIVE: We tested the effects of lipid-based nutrient supplements (LNS) that contained 1.3 times the Recommended Dietary Allowance of sodium selenite and antiretroviral drugs (ARV) on maternal plasma and breast-milk selenium concentrations. DESIGN: HIV-infected Malawian mothers in the Breastfeeding, Antiretrovirals, and Nutrition study were randomly assigned at delivery to receive: LNS, ARV, LNS and ARV, or a control. In a subsample of 526 mothers and their uninfected infants, we measured plasma and breast-milk selenium concentrations at 2 or 6 (depending on the availability of infant samples) and 24 wk postpartum. RESULTS: Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 µg/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 µg/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 µg/L) from 2 or 6 to 24 wk postpartum (all P < 0.001). Compared with the highest baseline selenium tertile, low and middle tertiles were positively associated with a change in maternal plasma or breast-milk selenium from 2 or 6 to 24 wk postpartum (both P < 0.001). With the use of linear regression, we showed that LNS that contained selenium and ARV were not associated with changes in maternal plasma and breast-milk selenium, but maternal selenium concentrations were positively associated with infant plasma selenium at 2 or 6 and 24 wk postpartum (P < 0.001) regardless of the study arm. CONCLUSIONS: Selenite supplementation of HIV-infected Malawian women was not associated with a change in their plasma or breast-milk selenium concentrations. Future research should examine effects of more readily incorporated forms of selenium (ie, selenomethionine) in HIV-infected breastfeeding women.
Assuntos
Antirretrovirais/uso terapêutico , Suplementos Nutricionais , Infecções por HIV/metabolismo , Lactação/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Leite Humano/química , Selênio/metabolismo , Adulto , Desenvolvimento Infantil , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Lactente , Lactação/sangue , Malaui , Estado Nutricional , Selênio/sangue , Selênio/deficiência , Selênio/uso terapêutico , Selenito de Sódio/administração & dosagem , Adulto JovemRESUMO
International guidelines recommend EBF to age 6 months among HIV-infected mothers choosing to breast-feed and cessation thereafter if replacement feeding is acceptable, feasible, affordable, sustainable, and safe. When mothers wean, they are challenged to provide an adequate replacement diet. This study investigates the use and acceptability of a lipid-based nutrient supplement (LNS) as a breast-milk substitute when provided to infants (6-12 mo) of HIV-positive mothers, as part of the Breast-feeding, Antiretroviral, and Nutrition (BAN) Study. A sub-sample of mothers (n = 45) participated in interviews that explored EBF, weaning, and strategies to feed LNS. Mothers reported several weaning strategies, including gradual reduction of breast-feeding, expressing breast-milk into a cup, and separation of mother and child. LNS, a peanut-based micronutrient fortified paste, was highly accepted and incorporated into the traditional diet. Weaning is a feasible HIV prevention method among this population in Malawi when supported by the provision of LNS as a breast-milk substitute.