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Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission.

ABSTRACT: OBJECTIVE:Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission. DESIGN:Prospective cohort study. METHODS:Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. Associations between postpartum antiretroviral adherence and rate of breast milk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. RESULTS:Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were less than 90% adherent. Having at least 90% adherence was associated with a 52% [95% confidence interval (CI) 3-76] relative reduction in the rate of breast milk HIV-1 transmission, compared with having less than 90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n?=?501; relative reduction 59%, 95% CI 6-82). CONCLUSION:Nonadherence to extended postpartum antiretroviral regimens in 'real world' settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of antiretroviral provision throughout breastfeeding.

SUBMITTER: Davis NL

PROVIDER: S-EPMC4397579 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission.

Davis Nicole L NL Miller William C WC Hudgens Michael G MG Chasela Charles S CS Sichali Dorothy D Kayira Dumbani D Nelson Julie A E JA Stringer Jeffrey S A JS Ellington Sascha R SR Kourtis Athena P AP Jamieson Denise J DJ van der Horst Charles C

AIDS (London, England) 20141101 18

<h4>Objective</h4>Estimate association between postpartum antiretroviral adherence and breast milk HIV-1 transmission.<h4>Design</h4>Prospective cohort study.<h4>Methods</h4>Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study. Associat ...[more]

PMID: 25493600

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Project description:Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the "six-week extended-dose nevirapine" (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.Standard population sequencing and cloning for viral subpopulations present at > or =5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant's blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.ClinicalTrials.gov NCT00061321.

Project description:INTRODUCTION:Older adults are generally considered to be at greater risk for medication non-adherence due to factors such as medication complexity, side effects, cost, and cognitive decline. However, this generalization may not apply to older adults with human immunodeficiency virus (HIV). Regardless of age, suboptimal adherence to antiretroviral therapy (ART) can lead to increased viral load, immunosuppression, drug-resistant viral strains, co-morbidities, and opportunistic infections. Understanding trends of adherence to ART among older adults is critical, especially as the population of people living with HIV grows older. OBJECTIVES:The purpose of this systematic review and meta-analysis is to determine if older individuals with HIV are less likely to be non-adherent to antiretroviral therapy than younger individuals with HIV. DESIGN:A systematic search in PubMed, Embase, and PsycINFO was conducted to identify peer-reviewed articles evaluating adherence to ART in older adults. Two independent reviewers screened abstracts, applied inclusion criteria, and appraised study quality. The bibliographies of qualifying studies were searched. Data were abstracted from studies by two independent authors. Meta-analyses were conducted, and adherence levels were reported as the relative risk of non-adherence in older individuals compared to younger individuals. RESULTS:The systematic search yielded 1,848 abstracts. Twelve studies met full inclusion criteria. The overall meta-analysis found that older age reduced risk for nonadherence by 27 % (relative risk (RR) 0.72, 95 % confidence interval (CI) 0.64–0.82). Studies assessing both short-term and long-term adherence demonstrated a significant reduction in non-adherence among older patients (RR 0.75, 95 % CI 0.64–0.87 and RR 0.65, 95 % CI 0.50–0.85, respectively). CONCLUSIONS:Older adults with HIV have a reduced risk for non-adherence to ART than their younger counterparts. Future studies should seek to elucidate contributing factors of adherence among older individuals with HIV.

Project description: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.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.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.Overall, mean (± SD) maternal (range: 81.2 ± 20.4 to 86.2 ± 19.9 ?g/L) and infant (55.6 ± 16.3 to 61.0 ± 15.4 ?g/L) plasma selenium concentrations increased, whereas breast-milk selenium concentrations declined (14.3 ± 11.5 to 9.8 ± 7.3 ?g/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.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.

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Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission.

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Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission.

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