Effects of early, abrupt weaning on HIV-free survival of children in Zambia.
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ABSTRACT: Background
In low-resource settings, many programs recommend that women who are infected with the human immunodeficiency virus (HIV) stop breast-feeding early. We conducted a randomized trial to evaluate whether abrupt weaning at 4 months as compared with the standard practice has a net benefit for HIV-free survival of children.Methods
We enrolled 958 HIV-infected women and their infants in Lusaka, Zambia. All the women planned to breast-feed exclusively to 4 months; 481 were randomly assigned to a counseling program that encouraged abrupt weaning at 4 months, and 477 to a program that encouraged continued breast-feeding for as long as the women chose. The primary outcome was either HIV infection or death of the child by 24 months.Results
In the intervention group, 69.0% of the mothers stopped breast-feeding at 5 months or earlier; 68.8% of these women reported the completion of weaning in less than 2 days. In the control group, the median duration of breast-feeding was 16 months. In the overall cohort, there was no significant difference between the groups in the rate of HIV-free survival among the children; 68.4% and 64.0% survived to 24 months without HIV infection in the intervention and control groups, respectively (P=0.13). Among infants who were still being breast-fed and were not infected with HIV at 4 months, there was no significant difference between the groups in HIV-free survival at 24 months (83.9% and 80.7% in the intervention and control groups, respectively; P=0.27). Children who were infected with HIV by 4 months had a higher mortality by 24 months if they had been assigned to the intervention group than if they had been assigned to the control group (73.6% vs. 54.8%, P=0.007).Conclusions
Early, abrupt cessation of breast-feeding by HIV-infected women in a low-resource setting, such as Lusaka, Zambia, does not improve the rate of HIV-free survival among children born to HIV-infected mothers and is harmful to HIV-infected infants.(ClinicalTrials.gov number, NCT00310726.)
SUBMITTER: Kuhn L
PROVIDER: S-EPMC2577610 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe previously reported no benefit of early weaning for HIV-free survival of children born to HIV-infected mothers in intent-to-treat analyses. Since early weaning was poorly accepted, we conducted a secondary analysis to investigate whether beneficial effects may have been hidden.Methods958 HIV-infected women in Lusaka, Zambia, were randomized to abrupt weaning at 4 months (intervention) or to continued breastfeeding (control). Children were followed to 24 months with regular HIV PCR tests and examinations to determine HIV infection or death. Detailed behavioral data were collected on when all breastfeeding ended. Most participants were recruited before antiretroviral treatment (ART) became available. We compared outcomes among mother-child pairs who weaned earlier or later than intended by study design adjusting for potential confounders.ResultsOf infants alive, uninfected and still breastfeeding at 4 months in the intervention group, 16.1% who weaned as instructed acquired HIV or died by 24 months compared to 16.0% who did not comply (p = 0.98). Children of women with less severe disease during pregnancy (not eligible for ART) had worse outcomes if their mothers weaned as instructed (RH = 2.60 95% CI: 1.06-6.36) compared to those who continued breastfeeding. Conversely, children of mothers with more severe disease (eligible for ART but did not receive it) who weaned early had better outcomes (p-value interaction = 0.002). In the control group, weaning before 15 months was associated with 3.94-fold (95% CI: 1.65-9.39) increase in HIV infection or death among infants of mothers with less severe disease.ConclusionIncomplete adherence did not mask a benefit of early weaning. On the contrary, for women with less severe disease, early weaning was harmful and continued breastfeeding resulted in better outcomes. For women with more advanced disease, ART should be given during pregnancy for maternal health and to reduce transmission, including through breastfeeding.Trial registration(ClinicalTrials.gov) NCT00310726.
| S-EPMC2698120 | biostudies-literature
Project description: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.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.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.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.NCT00310726.
| S-EPMC3069726 | biostudies-literature
Project description:Care of children living with HIV comprises various issues, some considered challenging. One of the challenging areas is the serostatus disclosure to HIV-positive children. This study describes the current situation of HIV disclosure among rural children in Zambia and examines the socio-demographic factors promoting disclosure.We used a mixed method approach applying both quantitative and qualitative methods to obtain comprehensive picture of HIV serostatus disclosure for children. Data were collected in Mumbwa district, Zambia (2010-2012), included 57 clinical records of children older than 5 years old. We examined children's age, gender, and cohabitation status with their parents, caregivers' level of education and income, and the relation between children and caregivers. Logistic regression model was applied to examine associations between disclosure and socio-demographic characteristics. Semi-structured interviews with 50 caregivers and 22 HIV-positive children were conducted to qualitatively investigate attitude towards disclosure and support needed.Full disclosure was completed in 17 out of 57 (29.8%) patients. Median ages of patients in disclosed group and non-disclosed group were 10 and 9, respectively (IQR 8.0-13.0, 7.0-11.25). In univariate analyses, older age and male gender has positive relation to the completion of serostatus disclosure. In logistic regression models, cohabitation status with patients' mothers showed positive correlation to the completion of serostatus disclosure. In the interviews with caregivers, all caregivers said that disclosure of serostatus is a necessary process and good for their children, while actual serostatus disclosure rate was low.Serostatus disclosure to HIV-seropositive children is not prevalent in Rural Zambia. Although further researches would be desirable, increased support to caregivers would be beneficial.
| S-EPMC6098826 | biostudies-other
Project description:BackgroundIn 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART.MethodsUsing a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods.ResultsOverall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3-8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4-1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6-16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3-6.4), compared to those aged 6-15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3-10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit.ConclusionWe observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.
| S-EPMC6348639 | biostudies-literature
Project description:OBJECTIVES:In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. DESIGN:We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). METHODS:We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). RESULTS:A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). CONCLUSIONS:This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.
| S-EPMC2814597 | biostudies-literature
Project description:BackgroundDespite being a preventable disease, pediatric HIV infection continues to be a public health concern due to the morbidity and mortality associated with the disease. Vertical transmission of HIV occurs when a mother living with HIV passes the virus to her baby during pregnancy, childbirth, or breastfeeding. Globally, the vertical transmission rate of HIV is 9% with sub-Saharan Africa accounting for 90% of these infections. In Kenya, the national vertical transmission rates of HIV stood at 11.5% by the end of 2018, with a target to reduce vertical transmission rates to below 5% and 2% in breastfeeding and non-breastfeeding infants respectively, by the end of 2021.ObjectiveTo determine the prognostic factors influencing HIV-free survival among infants enrolled for HIV early infant diagnosis (EID) services in selected hospitals in Nairobi County, Kenya.MethodsA prospective cohort study design was adopted. HIV exposed infants were recruited at six weeks to determine HIV-free survival over 12 months follow up. Simple random sampling was used to select 166 infants and data were collected from the mothers using semi-structured interviewer-administered questionnaires. Log-rank tests were used to test for associations at the bi-variable level while Cox-proportional regression was used to analyze data at the multi-variable level, with the aid of STATA 14 software. Ethical approval was obtained from Kenya Medical Research Institute, Scientific Ethics Review Unit.ResultsThe overall infant HIV incidence rate over one-year follow-up was 9 cases per 100 person-years (95% CI: 5.465-16.290). The failure event was defined as an infant with a positive PCR test during the study period with total failures being 13 (9.41%) over 12 months. Prognostic factors associated with poor infant HIV-free survival were young maternal age (18-24 years) and mothers with a recent HIV diagnosis of ≤ 2 years since a positive HIV diagnosis (HR 5.97 CI: 1.20, 29.58) and (HR 6.97 CI: 1.96, 24.76), respectively.ConclusionMaternal prognostic factors associated with poor infant HIV-free survival were young maternal age (18-24 years) and recent maternal HIV diagnosis of ≤ 2 years since positive HIV diagnosis. The study recommended the development of an intervention package with more rigorous adherence counseling and close monitoring for young mothers, and mothers with recent HIV diagnoses.
| S-EPMC10550113 | biostudies-literature
Project description:BackgroundMultiple previous studies have identified a detrimental effect of pediatric HIV on cognitive function. Socioeconomic status (SES) is one of the strongest predictors of cognitive performance and may affect the relationship between HIV and cognition.MethodsAs part of the ongoing HIV-Associated Neurocognitive Disorders in Zambia (HANDZ) study, a prospective cohort study, we recruited 208 participants with HIV and 208 HIV-exposed uninfected controls, all aged 8-17 years. A standardized questionnaire was administered to assess SES, and all participants had comprehensive neuropsychological testing. An NPZ8 score was derived as a summary measure of cognitive function. Logistic regression and linear regression were used to model the relationship between SES and cognitive function, and mediation analysis was used to identify specific pathways by which SES may affect cognition.ResultsChildren with HIV performed significantly worse on a composite measure of cognitive function (NPZ8 score -0.19 vs. 0.22, P < 0.001) and were more likely to have cognitive impairment (33% vs. 19%, P = 0.001). Higher SES was associated with reduced risk of cognitive impairment (odds ratio 0.8, 95% confidence interval: 0.75-0.92, P < 0.001) in both groups, with similar effects in children with HIV and HIV-exposed uninfected groups. SES was more strongly correlated with NPZ8 score in children with HIV than in uninfected controls (Pearson's R 0.39 vs. 0.28), but predicted NPZ8 in both groups. Mediation analysis suggested that the effect of SES on cognition was most strongly mediated through malnutrition.ConclusionsCognitive function is strongly correlated with SES in children with HIV, suggesting a synergistic effect of HIV and poverty on cognitive function.
| S-EPMC8794014 | biostudies-literature
Project description:BackgroundThe effect of breastfeeding on growth in HIV-exposed infants is not well described.ObjectiveThe objective was to evaluate the effect of early breastfeeding cessation on growth.DesignIn a trial conducted in Lusaka, Zambia, HIV-infected mothers were randomly assigned to exclusive breastfeeding for 4 mo followed by rapid weaning to replacement foods or exclusive breastfeeding for 6 mo followed by introduction of complementary foods and continued breastfeeding for a duration of the mother's choice. Weight-for-age z score (WAZ), length-for-age z score (LAZ), and weight-for-length z score (WLZ) and the self-reported breastfeeding practices of 593 HIV-uninfected singletons were analyzed. Generalized estimating equations were used to adjust for confounders.ResultsWAZ scores declined precipitously between 4.5 and 15 mo. The decline was slower in the breastfed infants. At 9, 12, and 15 mo, mean WAZs were, respectively, -0.74, -0.92, and -1.06 in infants who were reportedly breastfed and were -1.07, -1.20, and -1.31 in the weaned infants (P = 0.003, 0.007, and 0.02, respectively). No differences were observed past 15 mo. Breastfeeding practice was not associated with LAZ, which declined from -0.98 to -2.24 from 1 to 24 mo. After adjustment for birth weight, maternal viral load, body mass index, education, season, and marital and socioeconomic status, not breastfeeding was associated with a 0.28 decline in WAZ between 4.5 and 15 mo (P < 0.0001). During the rainy season, not breastfeeding was associated with a larger WAZ decline (0.33) than during the dry season (0.22; P for interaction = 0.02).ConclusionsEarly growth is compromised in uninfected children born to HIV-infected Zambian mothers. Continued breastfeeding partially mitigates this effect through 15 mo. Nutritional interventions to complement breastfeeding after 6 mo are urgently needed. This trial was registered at clinicaltrials.gov as NCT00310726.
| S-EPMC2709311 | biostudies-literature
Project description:The gastric mucosa is disturbed when breastfeeding is interrupted, and such early weaning (EW) condition permanently affects the differentiation of zymogenic cells. The aim of the study was to evaluate the immediate and long-term effects of EW on gastric cell proliferation, considering the molecular markers for cell cycle, inflammation, and metaplasia. Overall, we investigated the lifelong adaptation of gastric growth. Wistar rats were divided into suckling-control (S) and EW groups, and gastric samples were collected at 18, 30, and 60 days for morphology, RNA, and protein isolation. Inflammation and metaplasia were not identified, but we observed that EW promptly increased Ki-67-proliferative index (PI) and mucosa thickness (18 days). From 18 to 30 days, PI increased in S rats, whereas it was stable in EW animals, and such developmental change in S made its PI higher than in EW. At 60 days, the PI decreased in S, making the indices similar between groups. Spatially, during development, proliferative cells spread along the gland, whereas, in adults, they concentrate at the isthmus-neck area. EW pushed dividing cells to this compartment (18 days), increased PI at the gland base (60 days), but it did not interfere in expression of cell cycle molecules. At 18 days, EW reduced Tgfβ2, Tgfβ3, and Tgfbr2 and TβRII and p27 levels, which might regulate the proliferative increase at this age. We demonstrated that gastric cell proliferation is immediately upregulated by EW, corroborating previous results, but for the first time, we showed that such increased PI is stable during growth and aging. We suggest that suckling and early weaning might use TGFβs and p27 to trigger different proliferative profiles during life course.
| S-EPMC8475651 | biostudies-literature
Project description:BackgroundDespite the burden of HIV being highest in sub-Saharan Africa (SSA), research expertise and capacity to address scientific questions regarding complications of HIV and ART, especially chronic non-communicable conditions, is limited in the region. The comorbidities prevalent in persons with HIV are mediated through diverse mechanisms, many of which can be context or region-specific and are yet to be elucidated. The phenotype, risk factors, and effective interventions for these conditions may differ between populations and settings, and therefore there is an urgent need for research to help understand these processes and how to best address them in SSA. Here, we report the research capacity building activities in SSA conducted by the University of Zambia (UNZA)-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research (UVP), drawing lessons and challenges for a wide global health audience.MethodsWe reviewed program data and conducted interviews with program leaders and participants to understand and document the progress and outcomes of the partnership. We report the program's early achievements, highlighting drivers and challenges.ResultsBetween 2015 and 2019, UVP made substantial progress on its goals of training new UNZA PhD scientists to investigate complex nutritional and metabolic factors related to long-term HIV complications and comorbidities. The program has supported 11 UNZA PhD students with dual UNZA-Vanderbilt mentorship; three have graduated, and other candidates are progressing in their PhD studies. The project also supported institutional capacity through UNZA faculty participation in Vanderbilt grant writing workshops, with strong success in obtaining grants among those who participated. UVP also supported development of greater structure to UNZA's PhD program and a mentorship curriculum, both now adopted by UNZA. The major drivers for success included UVP's alignment of goals between UNZA and Vanderbilt, and local institutional ownership. The longstanding history of collaborations between the two institutions contributed substantially to alignment and mutual support of UVP's goals. Several challenges were noted, including limits on direct research funding for students and a relatively small pool of funded investigators at UNZA.ConclusionsDespite some challenges, UVP has achieved positive outcomes over its first four years. Longstanding partnerships and local institutional ownership were the main drivers. We expect the challenges to mitigated as the project continues and produces more UNZA researchers and teams and more funded projects, collectively building the local research community. With continued resources and clear focus, we expect that UNZA's investigators and partners will attract research funding and generate high-impact research outputs across a broad range of studies in HIV as well as newer threats from non-communicable conditions experienced by long-term survivors of HIV and by the general population.
| S-EPMC6838769 | biostudies-literature