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1.
Sci Rep ; 11(1): 3173, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542437

RESUMO

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

2.
Clin Infect Dis ; 71(4): 1030-1039, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31633158

RESUMO

BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.

4.
Medicine (Baltimore) ; 98(44): e17383, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689745

RESUMO

The risk of postnatal HIV transmission exists throughout the breastfeeding period. HIV shedding in breast milk beyond six months has not been studied extensively. The aim of this study was to determine prevalence and determinants of HIV shedding in breast milk during continued breastfeedingA cross-sectional study was nested in the PROMISE-PEP trial in Lusaka, Zambia to analyze breast milk samples collected from both breasts at week 38 post-partum (mid-way during continued breastfeeding). We measured concurrent HIV deoxyribonucleic acid (DNA) and HIV ribonucleic acid (RNA) as proxies for cell-associated HIV (CAV) and cell-free HIV (CFV) shedding in breast milk respectively. Participants' socio-demographic date, concurrent blood test results, sub clinical mastitis test results and contraceptive use data were available. Logistic regression models were used to identify determinants of HIV shedding in breast milk (detecting either CAV or CFV).The prevalence of HIV shedding in breast milk at 9 months post-partum was 79.4% (95%CI: 74.0 - 84.0). CAV only, CFV only and both CAV and CFV were detectable in 13.7%, 17.3% and 48.4% mothers, respectively. The odds of shedding HIV in breast milk decreased significantly with current use of combined oral contraceptives (AOR: 0.37; 95%CI: 0.17 - 0.83) and increased significantly with low CD4 count (AOR: 3.47; 95%CI: 1.23 - 9.80), unsuppressed plasma viral load (AOR: 6.27; 95%CI: 2.47 - 15.96) and severe sub-clinical mastitis (AOR: 12.56; 95%CI: 2.48 - 63.58).This study estimated that about 80% of HIV infected mothers not on ART shed HIV in breast milk during continued breastfeeding. Major factors driving this shedding were low CD4 count, unsuppressed plasma viral load and severe sub-clinical mastitis. The inverse relationship between breast milk HIV and use of combined oral contraceptives needs further clarification. Continued shedding of CAV may contribute to residual postnatal transmission of HIV in mothers on successful ART.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Leite Humano/virologia , Adulto , Antirretrovirais , Aleitamento Materno , Contagem de Linfócito CD4 , Ácidos Nucleicos Livres , Anticoncepcionais Orais Combinados/administração & dosagem , Estudos Transversais , DNA Viral , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa , Modelos Logísticos , Mastite/epidemiologia , Mães , Prevalência , RNA Viral , Fatores Socioeconômicos , Carga Viral , Eliminação de Partículas Virais/fisiologia , Adulto Jovem , Zâmbia
5.
Lancet HIV ; 6(5): e307-e314, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30814028

RESUMO

BACKGROUND: The tolerance of antiretroviral drugs in infants must be carefully evaluated. In previous studies of children with HIV type 1 (HIV-1) less weight gain was observed in children given lopinavir-ritonavir-based combinations than those given nevirapine. We aimed to compare the effects of lopinavir-ritonavir and lamivudine on growth in HIV-exposed uninfected infants included in the ANRS 12174 trial. METHODS: ANRS 12174 was a multicentre, randomised, controlled trial of infant prophylaxis to prevent HIV-1 transmission by breastfeeding done at four antenatal clinics in Burkina Faso, South Africa, Uganda, and Zambia. HIV-exposed uninfected infants born to asymptomatic mothers not eligible for antiretroviral therapy (CD4 count >350 cells per µL) were randomly assigned (1:1) to receive lopinavir-ritonavir or lamivudine 7 days after birth, with stratification by country. In a prespecified secondary analysis, we assessed the effect of lopinavir-ritonavir and lamivudine on the growth of these infants from day 7 until cessation of breastfeeding (maximum treatment time 12 months) in the modified intention-to-treat population, which included all children correctly enrolled with at least one follow-up anthropometric measurement. We compared the growth of infants, defined as children's WHO-defined length-for-age Z score (LAZ), weight-for-length Z score (WAZ), and weight-for-age Z score (WLZ). We used linear mixed effect and ß spline-regression models to compare growth between the treatment groups. The trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS: 1273 HIV-exposed uninfected infants and their mothers were enrolled between Nov 16, 2009, and May 7, 2013, of whom 1266 (99%) infants were included in the modified intention-to-treat analysis (630 assigned to lopinavir-ritonavir, 636 assigned to lamivudine). Baseline characteristics of the infants and mothers were similar across the two treatment groups. No differences in least-squares (LS) mean LAZ were identified between the treatment groups at any timepoint. LS mean WLZ was significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·22 [95% CI -0·34 to -0·09], p=0·0006) and 50 weeks (-0·25 [-0·47 to -0·04], p=0·02). LS mean WAZ was also significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·18 [95% CI -0·30 to -0·05], p=0·01) and 50 weeks (-0·24 [-0·45 to -0·05], p=0·02). Linear mixed models showed that lopinavir-ritonavir was associated with decreases in WLZ and WAZ over time (p<0·0001 and p=0·002), whereas spline regression models indicated that these reductions occurred early and remained constant thereafter (p<0·0001 with a knot at 44 days for WLZ; p=0·02 with a knot at 118 days for WAZ). The difference in LS mean WLZ at 50 weeks between the treatment groups was higher among girls than boys (difference -0·29 [95% CI -0·58 to 0·01], p=0·05 for girls; -0·22 [-0·53 to 0·09], p=0·18 for boys). INTERPRETATION: Less weight gain was observed in infants given lopinavir-ritonavir than those given lamivudine, which is indicative of a persistent effect that could have long-term deleterious effects. This finding merits attention considering the recommendations for early and lifelong treatment of infants with HIV. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis, the Total Foundation, the European Developing Countries Clinical Trials Partnership, and the Research Council of Norway.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Inibidores da Protease de HIV/farmacologia , HIV-1/imunologia , Humanos , Lamivudina/administração & dosagem , Lopinavir/administração & dosagem , Masculino , Ritonavir/administração & dosagem , Resultado do Tratamento , Carga Viral , Adulto Jovem
6.
Reprod Health ; 15(1): 55, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29587791

RESUMO

BACKGROUND: Adolescents living with HIV face challenges, such as disclosure of HIV status, adherence to antiretroviral therapy, mental health, and sexual and reproductive health (SRH). These challenges affect their future quality of life. However, little evidence is available on their sexual behaviors and SRH needs in Zambia. This study aimed at assessing their sexual behaviors and SRH needs and identifying factors associated with marriage concerns and a desire to have children. METHODS: This cross-sectional study was conducted at the University Teaching Hospital from April to July 2014. We recruited 200 adolescents aged 15-19 years who were aware of their HIV-positive status. We collected data on their first and recent sexual behavior, concerns about marriage, and desire to have children. We used the Generalized Linear Model to identify factors associated with having concerns about marriage and desire to have children. We performed thematic analysis with open-ended data to determine their perceptions about marriage and having children in the future. RESULTS: Out of 175 studied adolescents, 20.6% had experienced sexual intercourse, and only 44.4% used condoms during the first intercourse. Forty-eight percent had concerns about marriage, and 87.4% desired to have children. Marriage-related concerns were high among those who desired to have children (adjusted relative risk [ARR] = 2.51, 95% CI = 1.02 to 6.14). Adolescents who had completed secondary school were more likely to desire to have children (ARR = 1.35, 95% CI = 1.07 to 1.71). Adolescents who had lost both parents were less likely to want children (ARR = 0.80, 95% CI = 0.68 to 0.95). Thematic analysis identified that major concerns about future marriage were fear of disclosing HIV status to partners and risk of infecting partners and/or children. The reasons for their willingness to have children were the desire to be a parent, having children as family assets, a human right, and a source of love and happiness. CONCLUSIONS: Zambian adolescents living with HIV are at risk of engaging in risky sexual relationships and have difficulties in meeting needs of SRH. HIV care service must respond to a wide range of needs.


Assuntos
Comportamento do Adolescente , Soropositividade para HIV , Comportamento Reprodutivo , Comportamento Sexual , Adolescente , Comportamento do Adolescente/etnologia , Antirretrovirais/uso terapêutico , Estudos Transversais , Escolaridade , Saúde da Família/etnologia , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , Soropositividade para HIV/etnologia , Soropositividade para HIV/transmissão , Comportamentos Relacionados com a Saúde/etnologia , Inquéritos Epidemiológicos , Hospitais de Ensino , Humanos , Intenção , Masculino , Determinação de Necessidades de Cuidados de Saúde , Pesquisa Qualitativa , Comportamento Reprodutivo/etnologia , Saúde Reprodutiva/etnologia , Risco , Autorrevelação , Comportamento Sexual/etnologia , Zâmbia/epidemiologia
7.
AIDS Care ; 30(5): 634-642, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29347827

RESUMO

Physical and psychosocial changes during adolescence could influence the psychological well-being and adherence to antiretroviral therapy (ART) of adolescents living with HIV. However, few studies have assessed these two important issues in Zambia. This study aimed at addressing this gap by examining adolescents' depressive symptoms and ART adherence. This was a mixed-methods study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to 19, who were already aware of their HIV status. We measured depressive symptoms using the short form of the Center for Epidemiologic Studies Depression Scale, and self-reported three-day adherence to ART. We performed logistic regression analysis to identify factors associated with depressive symptoms and non-adherence to ART. For qualitative data, we examined challenges over ART adherence using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of depressive symptoms. Factors associated with depressive symptoms were unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95% Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI 1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non-adherent. Factors associated with non-adherence to ART were loss of a mother (AOR 3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI 1.43-7.40). Qualitative data identified the following challenges to ART adherence: management of medication, physical reactions to medicine, and psychosocial distress. The evidence suggests that depressive symptoms and non-adherence to ART were priority issues in late adolescence in Zambia. Health workers should be aware of these issues, and the care and treatment services should be tailored to respond to age-specific needs.


Assuntos
Depressão/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação/psicologia , Saúde Mental , Adolescente , Fármacos Anti-HIV/uso terapêutico , Depressão/diagnóstico , Relações Familiares/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Relações Profissional-Paciente , Escalas de Graduação Psiquiátrica , Autorrelato , Estigma Social , Adulto Jovem , Zâmbia
8.
Front Public Health ; 5: 326, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29326914

RESUMO

Background: HIV serostatus disclosure is an immense challenge for adolescents living with HIV, their caregivers, and health workers. In Zambia, however, little guidance is available from the adolescents' point of view on the HIV disclosure process. Objective: This study aimed to examine the setting of HIV serostatus disclosure for adolescents, its impacts on them, and their suggestions on the best practice of HIV disclosure. Methods: We conducted a mixed-methods study at the University Teaching Hospital in Zambia from April to July 2014. We recruited 200 adolescents living with HIV, aged 15-19 years. We collected data using a structured questionnaire including two open-ended questions. We excluded two adolescents due to withdrawal during the survey, and eight from the data set due to out-of-eligibility criteria in age. Eventually, we included 190 in the analysis. We performed descriptive analysis to calculate the distributions of basic characteristics of the adolescents, their experience and preference on HIV serostatus disclosure, its emotional and behavioral impacts, and health education topics they had ever learned at hospital. We performed thematic analysis with open-ended data to explain first impressions upon disclosure in detail and to determine perceived advantages of HIV serostatus disclosure. Results: The majority of adolescents recommended the age of 12 as appropriate for adolescents to learn about their HIV serostatus and preferred disclosure by both parents. Out of 190 adolescents, 73.2% had negative or mixed feelings about HIV serostatus disclosure, while 86.2% reported that disclosure was beneficial. Thematic analyses showed that the adolescents reacted emotionally due to an unexpected disclosure and a belief of imminent death from HIV. However, they improved adherence to treatment (84.7%), limited self-disclosure of their HIV serostatus to others (81.1%), and felt more comfortable in talking about HIV with their caregivers (54.2%). Thematic analysis identified perceived benefits of disclosure as follows: better understanding of their sickness and treatment, and improved self-care and treatment adherence. Lower percentage of the adolescents have learned about psychosocial well-being, compared to facts about HIV and treatment. Conclusion: Despite initial emotional distress experienced after the disclosure, knowing one's own HIV serostatus was found to be a crucial turning point for adolescents to improve motivation for self-care. HIV serostatus disclosure to adolescents requires follow-up support involving parents/primary caregivers, health workers, and peers.

9.
Medicine (Baltimore) ; 95(27): e4005, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27399077

RESUMO

Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratio ≥ 1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200 copies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.


Assuntos
Infecções por HIV/transmissão , HIV-1/fisiologia , Herpesvirus Humano 4/fisiologia , Transmissão Vertical de Doença Infecciosa , Mastite/virologia , Leite Humano/virologia , Eliminação de Partículas Virais , Adulto , Contagem de Linfócito CD4 , DNA Viral/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Recém-Nascido , RNA Viral/análise , Zâmbia
10.
Lancet ; 387(10018): 566-573, 2016 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-26603917

RESUMO

BACKGROUND: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding. METHODS: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per µL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group. INTERPRETATION: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding. FUNDING: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Aleitamento Materno , Infecções por HIV/prevenção & controle , HIV-1 , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Profilaxia Pré-Exposição/métodos , África ao Sul do Saara , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Lamivudina/administração & dosagem , Lopinavir/administração & dosagem , Ritonavir/administração & dosagem
11.
J Nutr ; 145(1): 66-72, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25527660

RESUMO

BACKGROUND: Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. OBJECTIVE: In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. METHODS: In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at <2 y of age; mothers of all HEU children who died at <2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. RESULTS: Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2'-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non-2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. CONCLUSIONS: The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.


Assuntos
Infecções por HIV/mortalidade , Infecções por HIV/transmissão , Leite Humano/química , Oligossacarídeos/análise , Complicações Infecciosas na Gravidez , Adulto , Animais , Aleitamento Materno , Estudos de Coortes , Feminino , Infecções por HIV/prevenção & controle , Humanos , Fatores Imunológicos , Lactente , Mortalidade Infantil , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Masculino , Leite , Prebióticos/análise , Gravidez , Trissacarídeos/análise , Zâmbia
12.
Pediatr Infect Dis J ; 32(12): e473-5, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23899964

RESUMO

Analysis of milk from 247 HIV-infected Zambian mothers showed that galectin-3 binding protein concentrations were significantly higher among HIV-infected mothers who transmitted HIV through breast-feeding (6.51 ± 2.12 µg/mL) than among nontransmitters but were also correlated with higher milk and plasma HIV RNA copies/mL and lower CD4+ cell counts. The association between galectin-3 binding protein and postnatal transmission was attenuated after adjustment for milk and plasma HIV load and CD4+ cell counts. This suggests that although milk galectin-3 binding protein is a marker of advanced maternal disease, it does not independently modify transmission risk.


Assuntos
Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Aleitamento Materno , Proteínas de Transporte/análise , Glicoproteínas/análise , Infecções por HIV/transmissão , Transmissão Vertical de Doença Infecciosa , Leite Humano/química , Leite Humano/virologia , Estudos de Casos e Controles , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/metabolismo , Humanos , Fatores de Risco , Carga Viral , Zâmbia/epidemiologia
13.
Sci Transl Med ; 5(181): 181ra51, 2013 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-23596203

RESUMO

Concentrations of HIV-1 RNA and DNA in mucosal compartments influence the risk of sexual transmission and mother-to-child transmission of HIV-1. Breast milk production is physiologically regulated such that supply is a function of infant demand, but whether demand also influences HIV-1 dynamics in breast milk is unknown. We tested whether minor and major changes in feeding frequency influence breast milk viral concentrations in 958 HIV-1-infected women and their infants followed, for 24 months during a trial in Lusaka, Zambia. Women were randomized to wean abruptly at 4 months or to continue breast-feeding for a duration of their own choosing. Two weeks after breast-feeding cessation (4.5 months), HIV-1 concentrations in breast milk were substantially higher (median RNA, 2708 copies/ml; DNA, 14 copies/ml) than if breast-feeding continued (median RNA, <50 copies/ml; DNA, <1 copy/ml; P < 0.0001). Among those continuing breast-feeding, HIV-1 concentrations in milk were higher if breast-feeding was nonexclusive (median RNA, 293 copies/ml; DNA, 2 copies/ml; P = 0.0006). Elevated milk viral concentrations after stopping breast-feeding explained higher than expected rates of late postnatal HIV transmission in those who weaned early. Changes in the frequency of breast-feeding peri-weaning and with nonexclusive breast-feeding influenced milk viral concentrations. This may explain the reduced risk of HIV-1 transmission associated with exclusive breast-feeding and why early weaning does not achieve the magnitude of HIV prevention predicted by models. Our results support continuation of maternal antiretroviral drug interventions over the full duration of time when any breast milk exposures may occur after planned weaning.


Assuntos
HIV-1/isolamento & purificação , Leite Humano/virologia , Desmame , Mama/patologia , Aleitamento Materno , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , RNA Viral/análise , Fatores de Risco , Fatores de Tempo , Zâmbia/epidemiologia
14.
BMC Pediatr ; 12: 138, 2012 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-22937874

RESUMO

BACKGROUND: HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status. METHODS: A total of 1229 HIV-infected pregnant women were enrolled (2001-2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods. RESULTS: The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10-3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46-6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02-1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25-6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection. CONCLUSIONS: More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.


Assuntos
Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Infecções por HIV/complicações , Doenças do Recém-Nascido/mortalidade , Complicações Infecciosas na Gravidez , Natimorto/epidemiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Adulto Jovem
15.
Am J Clin Nutr ; 96(4): 831-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22894939

RESUMO

BACKGROUND: The inefficiency of HIV breast-milk transmission may be caused by the presence of immunologically active factors, including human milk oligosaccharides (HMOs). OBJECTIVE: We investigated whether HMO concentrations are associated with a reduced risk of postnatal HIV transmission. DESIGN: A nested case-control study was conducted within a larger cohort study of HIV-infected women and their infants followed from birth to 24 mo in Lusaka, Zambia. Breast-milk samples collected at 1 mo from 81 HIV-infected women who transmitted via breastfeeding, a random sample of 86 HIV-infected women who did not transmit despite breastfeeding, and 36 uninfected breastfeeding women were selected. Total and specific HMO concentrations were measured by HPLC and compared between groups with adjustment for confounders by using logistic regression. RESULTS: HIV-infected women with total HMOs above the median (1.87 g/L) were less likely to transmit via breastfeeding (OR: 0.45; 95% CI: 0.21, 0.97; P = 0.04) after adjustment for CD4 count and breast-milk HIV RNA concentrations; a trend toward higher concentrations of lacto-N-neotetraose being associated with reduced transmission (OR: 0.49; 95% CI: 0.23, 1.04; P = 0.06) was also observed. The proportion of 3'-sialyllactose (3'-SL) per total HMOs was higher among transmitting than among nontransmitting women (P = 0.003) and correlated with higher plasma and breast-milk HIV RNA and lower CD4 counts. Neither Secretor nor Lewis status distinguished between transmitting and nontransmitting women. CONCLUSIONS: Higher concentrations of non-3'-SL HMOs were associated with protection against postnatal HIV transmission independent of other known risk factors. Further study of these novel, potentially anti-HIV components of breast milk is warranted.


Assuntos
Aleitamento Materno , Infecções por HIV/transmissão , HIV/patogenicidade , Leite Humano/química , Leite Humano/virologia , Oligossacarídeos/análise , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Estudos de Coortes , Fatores de Confusão Epidemiológicos , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Lactação , Antígenos do Grupo Sanguíneo de Lewis/metabolismo , Masculino , Leite Humano/metabolismo , Oligossacarídeos/metabolismo , RNA Viral/análise , RNA Viral/sangue , Risco , Adulto Jovem , Zâmbia/epidemiologia
16.
J Infect Dis ; 203(9): 1222-30, 2011 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-21459815

RESUMO

BACKGROUND: Early weaning may reduce human immunodeficiency virus (HIV) transmission but may have deleterious consequences for uninfected children. Here we evaluate effects of early weaning on diarrhea morbidity and mortality of uninfected children born to HIV-infected mothers. METHODS: HIV-infected women in Lusaka, Zambia, were randomly assigned to breastfeeding for 4 months only or to continue breastfeeding until the mother decided to stop. Replacement and complementary foods were provided and all women were counseled around feeding and hygiene. Diarrhea morbidity and mortality were assessed in 618 HIV-uninfected singletons alive and still breastfeeding at 4 months. Intent-to-treat analyses and comparisons based on actual feeding practices were conducted using regression methods. RESULTS: Between 4 and 6 months, diarrheal episodes were 1.8-fold (95% confidence interval (CI), 1.3-2.4) higher in the short compared with long breastfeeding group. Associations were stronger based on actual feeding practices and persisted after adjustment for confounding. At older ages, only more severe outcomes, including diarrhea-related hospitalization or death (relative hazard [RH], 3.2, 95% CI, 2.1-5.1 increase 4-24 months), were increased among weaned children. CONCLUSIONS: Continued breastfeeding is associated with reduced risk of diarrhea-related morbidity and mortality among uninfected children born to HIV-infected mothers in this low-resource setting despite provision of replacement and complementary food and counseling. CLINICAL TRIALS REGISTRATION: NCT00310726.


Assuntos
Diarreia/epidemiologia , Diarreia/mortalidade , Desmame , Pré-Escolar , Feminino , Infecções por HIV/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Análise de Sobrevida , Zâmbia/epidemiologia
17.
AIDS ; 24(9): 1374-7, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20568677

RESUMO

We reviewed the potential impact of new WHO criteria for antiretroviral therapy using data from 1025 HIV-infected women and infants followed for 24 months in Lusaka, Zambia. The new criteria require initiating therapy among 68% of pregnant women and, if fully effective, would prevent 92% of maternal deaths and 88% of perinatal and postnatal infections. Using CD4 cell count below 350 cells/microl, irrespective of clinical stage, is more efficient and stricter CD4 cutoffs would be counter productive.


Assuntos
Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Humanos , Gravidez , Carga Viral , Organização Mundial da Saúde , Zâmbia
18.
Int J Epidemiol ; 39(5): 1299-310, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20484334

RESUMO

BACKGROUND: There are concerns about effects of lactation on postpartum weight changes among HIV-infected women because low weight may increase risks of HIV-related disease progression. METHODS: This analysis of postpartum maternal weight change is based on a trial evaluating the effects of shortened breastfeeding on postpartum mother-to-child transmission of HIV in Lusaka, Zambia, in which 958 HIV-infected women were randomized to breastfeed for a short duration (4 months) or for a duration of their own informed choosing (median 16 months). Among 768 women who met inclusion criteria, we compared across the two groups change in weight (kg) and the percent underweight [body mass index (BMI) <18.5] through 24 months. We also examined the effect of breastfeeding in two high-risk groups: those with low BMI and those with low CD4 counts. RESULTS: Overall, women in the long-duration group gained less weight compared with those in the short-duration group from 4-24 months {1.0 kg [95% confidence interval (CI): 0.3-1.7] vs 2.3 kg (95% CI: 1.6-2.9), P = 0.01}. No association was found between longer breastfeeding and being underweight (odds ratio 1.1; 95% CI: 0.8-1.6; P = 0.40). Effects of lactation in underweight women and women with low CD4 counts were similar to the effects in women with higher BMI and higher CD4 counts. Women with low baseline BMI tended to gain more weight from 4 to 24 months than those with higher BMI, regardless of breastfeeding duration (2.1 kg, 95% CI: 1.3-2.9; P < 0.01). CONCLUSIONS: In this study of HIV-infected breastfeeding women in a low-resource setting, the average change in weight from 4 to 24 months postpartum was a net gain rather than loss. Although longer duration breastfeeding was associated with less weight gain, breastfeeding duration was not associated with being underweight (BMI < 18.5). Weight change associated with longer breastfeeding may be metabolically regulated so that women with low BMI and at risk of wasting are protected from excess weight loss.


Assuntos
Aleitamento Materno , Infecções por HIV , Ganho de Peso , Índice de Massa Corporal , Progressão da Doença , Feminino , Infecções por HIV/fisiopatologia , Humanos , Fatores de Risco , Fatores Socioeconômicos , Magreza , Fatores de Tempo , Zâmbia/epidemiologia
19.
Clin Infect Dis ; 50(3): 437-44, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20047479

RESUMO

BACKGROUND: Early weaning has been recommended to reduce postnatal human immunodeficiency virus (HIV) transmission. We evaluated the safety of stopping breast-feeding at different ages for mortality of uninfected children born to HIV-infected mothers. METHODS: During a trial of early weaning, 958 HIV-infected mothers and their infants were recruited and followed up from birth to 24 months postpartum in Lusaka, Zambia. One-half of the cohort was randomized to wean abruptly at 4 months, and the other half of the cohort was randomized to continue breast-feeding. We examined associations between uninfected child mortality and actual breast-feeding duration and investigated possible confounding and effect modification. RESULTS: The mortality rate among 749 uninfected children was 9.4% by 12 months of age and 13.6% by 24 months of age. Weaning during the interval encouraged by the protocol (4-5 months of age) was associated with a 2.03-fold increased risk of mortality (95% confidence interval [CI], 1.13-3.65), weaning at 6-11 months of age was associated with a 3.54-fold increase (95% CI, 1.68-7.46), and weaning at 12-18 months of age was associated with a 4.22-fold increase (95% CI, 1.59-11.24). Significant effect modification was detected, such that risks associated with weaning were stronger among infants born to mothers with higher CD4(+) cell counts (>350 cells/microL). CONCLUSION: Shortening the normal duration of breast-feeding for uninfected children born to HIV-infected mothers living in low-resource settings is associated with significant increases in mortality extending into the second year of life. Intensive nutritional and counseling interventions reduce but do not eliminate this excess mortality.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Mortalidade/tendências , Análise de Sobrevida , Desmame , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Mães , Zâmbia/epidemiologia
20.
BMC Infect Dis ; 9: 195, 2009 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-19954529

RESUMO

BACKGROUND: Treatment of cryptosporidiosis in HIV infected children has proved difficult and unsatisfactory with no drugs having demonstrable efficacy in controlled trials except nitazoxanide. We hypothesised that a prolonged course of treatment with high dose nitazoxanide would be effective in treating cryptosporidiosis in HIV positive Zambian children. METHODS: We performed a double-blind, randomised, placebo controlled trial in paediatric patients in the UTH in Lusaka. The study included HIV positive children between one and eleven years of age if 2 out of 3 stool samples were positive for oocysts of Cryptosporidium spp. Children were given nitazoxanide suspension in a dose of 200 mg twice daily (bid) for 28 days (if 1-3 years old) or 400 mg bid for 28 days (if 4-11 years old), or matching placebo. RESULTS: Sixty children were randomised and 52 were fully evaluated. Only five children were 4 years of age or over and received the higher dose. In the primary efficacy analysis, 11 out of 26 (42%) in the active treatment group achieved a 'Well' clinical response compared to 8 out of 26 (35%) in the placebo group. Parasitological response was declared as 'Eradicated' in 27% in the active group and 35% in the placebo group. Mortality (16/52, 31%) did not differ by treatment allocation. CONCLUSION: We found no significant benefit in children with cryptosporidiosis despite high dose and longer treatment duration. This is the second randomised controlled trial to suggest that in Zambian children with HIV-related immunosuppression nitazoxanide does not eradicate this infection nor provide clinical symptom reduction. TRIAL REGISTRATION: The trial was registered as ISRCTN41089957.


Assuntos
Antiparasitários/uso terapêutico , Criptosporidiose/tratamento farmacológico , Soropositividade para HIV/complicações , Tiazóis/uso terapêutico , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento , Zâmbia
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