Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

Chasela, Charles; Hudgens, Michael G.; Jamieson, Denise J.; Kayira, Dumbani; Hosseinipour, Mina C.; Kourtis, Athena P.; Martinson, Francis; Tegha, Gerald; Knight, R. J.; Ahmed, Yusuf; Kamwendo, Deborah; Hoffman, Irving; Ellington, Sascha; Kacheche, Zebrone; Soko, Alice; Wiener, Jeffrey; Fiscus, Susan A.; Kazembe, Peter N.; Mofolo, Innocent; Chigwenembe, Maggie; Sichali, Dorothy; Horst, Charles M. van der

doi:10.1056/nejmoa0911486

Cited by 386 publications

(235 citation statements)

References 19 publications

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“…This study provided a unique opportunity to investigate humoral correlates of reduced postnatal mother-to-child transmission risk in the absence of postnatal antiretroviral therapy (20). Although no statistically significant associations were identified in the primary logistic regression models after correction for multiple comparisons, in subsequent exploratory analysis, the breast milk IgA responses against B.con env03 gp140 Env were associated with reduced HIV-1 postnatal transmission risk by two independent but related measures: total IgA binding by single-antigen ELISA and SIgA binding by BAMA.…”

Section: Discussionmentioning

confidence: 99%

“…This study enrolled antiretroviral-naive, HIV-1-infected pregnant women in Malawi with CD4 ϩ T cell counts above 200 cells/l (250 cells/l after 24 July 24 2006) from 2004 to 2009. All mothers and infants in the control arm received single-dose nevirapine at onset of labor (postpartum for infants), followed by 7 days of zidovudine/lamivudine therapy (20). Mothers who transmitted HIV-1 to their infants during breastfeeding (n ϭ 22) were included in the current study and matched in a near 1:3 ratio with nontransmitting mothers (n ϭ 65) for postpartum visit and the closest peripheral CD4…”

Section: Methodsmentioning

confidence: 99%

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Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Pollara

McGuire

Fouda

et al. 2015

J Virol

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Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCEInfants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Pollara

McGuire

Fouda

et al. 2015

J Virol

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“…The BAN study was a randomized controlled clinical trial that evaluated, in a factorial design, the safety and efficacy of (i) antiretroviral prophylaxis (a maternal triple-drug antiretroviral regimen versus infant daily nevirapine administered during 28 weeks of breastfeeding versus a control arm of only 1 week of antiretroviral prophylaxis after delivery) and (ii) a maternal nutritional supplement during breastfeeding in reducing postnatal mother-to-child HIV transmission and in enhancing maternal health during breastfeeding (19). The study randomized and followed 2,369 mother-infant pairs between 2004 and 2010 in Lilongwe, Malawi; enrolled infants had to have a birth weight of at least 2,000 g and be HIV uninfected by 2 weeks of age.…”

Section: Methodsmentioning

confidence: 99%

“…Given the presence of maternal transplacentally acquired antibody in the infant and the high prevalence of CMV immunity among women in resource-limited settings, antibody avidity was used as a tool to decipher the time of primary CMV infection in the infants. We used samples collected and stored from infants enrolled in the Breastfeeding, Antiretrovirals and Nutrition (BAN) study (19), who breastfed for 28 weeks and were followed for their first 48 weeks of life in Lilongwe, Malawi.…”

mentioning

confidence: 99%

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Kourtis¹,

Wiener²,

Chang³

et al. 2015

Clin. Vaccine Immunol.

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dCytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIVexposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants ( C ytomegalovirus (CMV) infection is the most common congenital infection, with an estimated prevalence of Ͼ1% in resource-limited settings (1, 2). Approximately 10 to 20% of congenital CMV infections result in permanent deficits, including sensorineural hearing loss, vision loss, and mental and developmental disability (3). The postnatal acquisition of CMV can occur through horizontal transmission and through breastfeeding, with a high probability of transmission in infants fed with breast milk containing infectious virus (4, 5). The infants of HIV-infected mothers may have higher rates of congenital CMV infection, particularly if the mothers are immunocompromised (6). While postnatal transmission is thought to be generally benign in healthy full-term infants, premature infants or other groups of immunocompromised infants are at risk for more extensive disease and may also experience long-term cognitive delays (7-9).While the increased morbidity and mortality among infants coinfected with HIV and CMV is well recognized (10-14), HIVexposed but uninfected infants may also be at increased risk for morbidity and mortality from CMV infection (15-17). A study in Zambia found that HIV-exposed infants who were CMV seropositive had decreased length for age, reduced head size, and lower psychomotor development than those who were CMV uninfected (5). HIV is endemic in many African countries and the CMV childhood infection burden is high, which may have a substantial impact on child health in the region. It is therefore important to examine when infants acquire primary CMV infection in such settings.In a previous analysis, we reported, using blood CMV PCR, that Ͼ70% of infants of HIV-infected mothers had acquired CMV infection by 24 weeks of age (18). Given that blood is not the optimal sample source for CMV detection, it is possible that our findings underestimated the true incidence of CMV acquisition in the infants. We thus additionally performed CMV IgG antibody titer and avidity testing in the infant plasma specimens at different points in the infants' first year of life. The objectives of this study were to comprehensively assess the rate of CMV acquisition and to further characterize the time of CMV infection in HIV-exp...

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“…These studies demonstrated significant reduction in the risk of motherto-child transmission of HIV by administering ARV medications to the mother or the infant during the breastfeeding period (Chasela et al, 2010). We have found no studies specifically undertaken to make replacement feeding safer for infants unable to breast-feed, whether HIV exposed or unexposed.…”

mentioning

confidence: 99%

Practices and recommendations in infant feeding and HIV prevention: the child's perspective

Torres¹,

Bedell

Wachira

et al. 2014

AIDS Care

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Although the attainment of Millennium Development Goal 4 (MDG 4), reducing under-five mortality by two-thirds by the year 2015, depends on optimizing breast-feeding practices in resource-limited settings, there are some conditions in which breast-feeding is impossible, contraindicated, or not recommended. The overall impact of involuntary nonbreast-feeding on the attainment of MDG 4 has not been documented. In industrialized and many middle-income countries replacement feeding is affordable, feasible, acceptable, sustainable, and safe and complete avoidance of breast-feeding is the norm to prevent postnatal transmission of HIV. The situation is very different in many low-income countries affected by the HIV epidemic where infants are exposed to HIV and antiretroviral (ARV) mediation through breast milk for long periods with risk of acquiring HIV infection, development of multidrug resistant HIV and short and long term toxicity associated to ARV medications. Despite the obvious needs, there is no specific research on how to make replacement feeding safer for infants with no access to breast-feeding and for whom replacement feeding is justified. Orphans, abandoned and infants of severely ill mothers unable to breast-feed, won't benefit from the research done on making breast-feeding safer for HIV exposed infants. A child rights perspective illuminates societal obligations to provide replacement feeding with infant formula milk to such infants, and to support research to make it safer at the same time that breast-feeding is promoted and protected for the general population.

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Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

Cited by 386 publications

References 19 publications

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

Practices and recommendations in infant feeding and HIV prevention: the child's perspective

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