Biomaterial Database

Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. 2009

Anitha Moorthy, and Amita Gupta, and Ramesh Bhosale, and Srikanth Tripathy, and Jayagowri Sastry, and Smita Kulkarni, and Madhuri Thakar, and Renu Bharadwaj, and Anju Kagal, and Arvind V Bhore, and Sandesh Patil, and Vandana Kulkarni, and Varadharajan Venkataramani, and Usha Balasubramaniam, and Nishi Suryavanshi, and Carrie Ziemniak, and Nikhil Gupte, and Robert Bollinger, and Deborah Persaud

Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

BACKGROUND 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. RESULTS 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. CONCLUSIONS 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. BACKGROUND ClinicalTrials.gov NCT00061321.

UI	MeSH Term	Description	Entries
D007223	Infant	A child between 1 and 23 months of age.	Infants
D007231	Infant, Newborn	An infant during the first 28 days after birth.	Neonate,Newborns,Infants, Newborn,Neonates,Newborn,Newborn Infant,Newborn Infants
D008297	Male		Males
D008895	Milk, Human	Milk that is produced by HUMAN MAMMARY GLANDS.	Breast Milk,Human Milk,Milk, Breast
D011247	Pregnancy	The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	Gestation,Pregnancies
D011251	Pregnancy Complications, Infectious	The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION.	Complications, Infectious Pregnancy,Infectious Pregnancy Complications,Maternal Sepsis,Pregnancy, Infectious Complications,Sepsis during Pregnancy,Sepsis in Pregnancy,Infectious Pregnancy Complication,Pregnancy Complication, Infectious,Sepsis in Pregnancies,Sepsis, Maternal
D001942	Breast Feeding	The nursing of an infant at the breast.	Breast Fed,Breastfed,Milk Sharing,Wet Nursing,Breast Feeding, Exclusive,Breastfeeding,Breastfeeding, Exclusive,Exclusive Breast Feeding,Exclusive Breastfeeding,Sharing, Milk
D005260	Female		Females
D005838	Genotype	The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.	Genogroup,Genogroups,Genotypes
D006678	HIV	Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.	AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated