Drug Resistance in Plasma and Breast Milk after Single-Dose Nevirapine in Subtype C HIV Type 1: Population and Clonal Sequence Analysis

Kassaye, Seble; Lee, Esther; Kantor, Rami; Johnston, Elizabeth; Winters, Mark A.; Zijenah, Lynn S.; Mateta, Patrick; Katzenstein, David

doi:10.1089/aid.2007.0045

Cited by 28 publications

(27 citation statements)

References 17 publications

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“…In the management of infants, utilising CNSpenetrating regimens are not always possible. Single-dose NVP (sd-NVP) is widely used in sub-Saharan Africa in the prophylactic treatment of infants in the management of PMTCT; however there is controversy over its use due to the emergence of NNRTI resistance mutations developing readily (Arrivé, et al, 2007;Kassaye, et al, 2007).…”

Section: Antiretroviral Eramentioning

confidence: 99%

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Hutchings¹,

Potterton

2013

Vulnerable Children and Youth Studies

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The aim of this cross-sectional study was to determine the difference in development (cognition; receptive and expressive language; and fine and gross motor) of Human Immunodeficiency Virus (HIV) -exposed infected (HEI) infants with the development of HIV-exposed but uninfected (HEU) infants using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Sixty infants were enrolled in the study; 32 (53.33%) HEU infants and 28 (46.67%) HEI infants. The two groups were well-matched for infant demographics, anthropometry at birth, maternal demographics, as well as socioeconomic status. Statistically significant differences were found in anthropometry and development between the HEI and HEU group. The HEI infants had malnutrition, were stunted and had smaller head circumferences than HEU infants. The BSID-III showed that the mean developmental delay for the HEI group was approximately two months below their mean chronological age for all scales (cognitive; receptive and expressive communication; and, fine and gross motor age).The HEI group showed that 64.29% had cognitive delay, 60.71% had language delay and 53.57% had motor delay, all of which was significantly different from the development of the HEU group for all domains (p<0.001). In addition to using the BSID-III, the majority of mothers were able to correctly indicate whether their child was developing at the same, or at a slower rate of development than children of the same age. This study demonstrates that infants who are HIV-exposed and infected are at risk of developmental delay.

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Section: Antiretroviral Eramentioning

confidence: 99%

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Hutchings¹,

Potterton

2013

Vulnerable Children and Youth Studies

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“…So far, only three studies have determined the emergence of NVP-resistant virus in breast milk following intake of NVP-SD. Two studies analysed breast milk of women infected with HIV-1 subtype C and showed that HIV-1 variants in breast milk emerged frequently and often differed in sequences from resistant HIV-1 variants in plasma [13,14]. Recently, a third study analysed breast milk samples of women mainly infected with HIV-1 subtypes A and D using a population-based approach with a detection limit for drug-resistant HIV-1 variants of approximately 20% [15].…”

Section: Introductionmentioning

confidence: 99%

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

et al. 2011

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“…Participant plasma samples were collected from the Malaria and HIV-1 in Pregnancy (MHP) prospective cohort. [17][18][19][20] The MHP study was approved by the Malawi College of Medicine Research Committee and the Institutional Review Board at the University of North Carolina at Chapel Hill. Informed consent was obtained from all mothers.…”

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confidence: 99%

“…Informed consent was obtained from all mothers. Women and their newborn infants received single-dose nevirapine according to the HIV-NET 012 protocol 20 and breastfeeding was initiated. Plasma and cell pellets were isolated from blood collected from the mothers at labor-ward admission, and blood was collected via heel-sticks from the infants at three time points: within 48 h of birth, at 6 weeks, and at 12 weeks of age.…”

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confidence: 99%

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Russell

Ojeda

Fouda

et al. 2013

AIDS Research and Human Retroviruses

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Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, we address the question of whether specific viral characteristics are common to variants transmitted through breastfeeding that may facilitate evasion of innate or adaptive immune responses. We amplified the envelope gene (env) from the plasma of six infants during acute infection who were infected with HIV-1 subtype C through breastfeeding, and from three available matched maternal samples. We sequenced the full-length env genes in these subjects revealing heterogeneous viral populations in the mothers and homogeneous populations in the infants. In five infants, the viral population arose from a single variant, while two variants were detected in the remaining infant. Infant env sequences had fewer N-linked glycosylation sites and shorter sequences than those of the available matched maternal samples. Though the small size of the study precluded our ability to test statistical significance, these results are consistent with selection for virus with shorter variable loops and fewer glycosylation sites during transmission of HIV-1 subtype C in other settings. Transmitted envs were resistant to neutralization by antibodies 2G12 and 2F5, but were generally sensitive to the more broadly neutralizing PG9, PG16, and VRC01, indicating that this new generation of broadly neutralizing monoclonal antibodies could be efficacious in passive immunization strategies.T ransmission of human immunodeficiency virus-1 (HIV-1) through breastfeeding (BF) makes up one-third to one-half of all mother-to-child transmission events.1 The mechanism(s) of transmission, however, are poorly understood. The oral cavity and gastrointestinal tract of breastfed infants are exposed daily to both cell-free and cell-associated HIV-1, 2-4 yet the majority of infants remain uninfected even if neither mother nor baby receive antiretroviral prophylaxis. 5This inefficiency of transmission indicates that anatomical, innate, and/or adaptive mechanisms of protection are able to prevent transmission to a great extent.6-11 Maternal antibodies could prevent infection either through direct binding of virus in the breast milk, or by their systemic and mucosal presence in the infant. This passive maternal immunity in the infant increases in concentration during the last trimester of gestation, and continues to pass into the infant through breastfeeding.Studies of in utero and intrapartum transmission have shown a universal bottleneck in genetic diversity from mother to child, as well as differences in the characteristics of transmitted virus for in utero versus intrapartum transmission. 12,13 Data are very limited for breastfeeding pairs, but one study of three breast milk transmission events found a similar bottleneck for HIV-1 subtype A.14 We previously demonstrated that the viral population found in ...

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Drug Resistance in Plasma and Breast Milk after Single-Dose Nevirapine in Subtype C HIV Type 1: Population and Clonal Sequence Analysis

Cited by 28 publications

References 17 publications

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Developmental delay in HIV-exposed infants in Harare, Zimbabwe

Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

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