Clonal amplification and maternal-infant transmission of nevirapine-resistant HIV-1 variants in breast milk following single-dose nevirapine prophylaxis.
BACKGROUND
Intrapartum administration of single-dose nevirapine (sdNVP) reduces perinatal HIV-1 transmission in resource-limiting settings by half. Yet this strategy has limited effect on subsequent breast milk transmission, making the case for new treatment approaches to extend maternal/infant antiretroviral prophylaxis through the period of lactation. Maternal and transmitted infant HIV-1 variants frequently develop NVP resistance mutations following sdNVP, complicating subsequent treatment/prophylaxis regimens. However, it is not clear whether NVP-resistant viruses are transmitted via breastfeeding or arise de novo in the infant.


RESULTS
We performed a detailed HIV genetic analysis using single genome sequencing to identify the origin of drug-resistant variants in an sdNVP-treated postnatally-transmitting mother-infant pair. Phylogenetic analysis of HIV sequences from the child revealed low-diversity variants indicating infection by a subtype C single transmitted/founder virus that shared full-length sequence identity with a clonally-amplified maternal breast milk virus variant harboring the K103N NVP resistance mutation.


CONCLUSIONS
In this mother/child pair, clonal amplification of maternal NVP-resistant HIV variants present in systemic and mammary gland compartments following intrapartum sdNVP represents one source of transmitted NVP-resistant variants that is responsible for the acquisition of drug resistant virus by the breastfeeding infant. This finding emphasizes the need for combination antiretroviral prophylaxis to prevent mother-to-child HIV transmission.
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA.
Sallie R
SR
Permar
Maria G
MG
Salazar
Feng
F
Gao
Fangping
F
Cai
Gerald H
GH
Learn
Linda
L
Kalilani
Beatrice H
BH
Hahn
George M
GM
Shaw
Jesus F
JF
Salazar-Gonzalez
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018890:Chemoprevention / Q000379:methods; D016000:Cluster Analysis; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008895:Milk, Human / Q000821:virology*; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D019829:Nevirapine / Q000008:administration & dosage* / Q000494:pharmacology; D010802:Phylogeny; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019829:Nevirapine