Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants.
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.
Moorthy
Anitha
A
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Gupta
Amita
A
Bhosale
Ramesh
R
Tripathy
Srikanth
S
Sastry
Jayagowri
J
Kulkarni
Smita
S
Thakar
Madhuri
M
Bharadwaj
Renu
R
Kagal
Anju
A
Bhore
Arvind V
AV
Patil
Sandesh
S
Kulkarni
Vandana
V
Venkataramani
Varadharajan
V
Balasubramaniam
Usha
U
Suryavanshi
Nishi
N
Ziemniak
Carrie
C
Gupte
Nikhil
N
Bollinger
Robert
R
Persaud
Deborah
D
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001942:Breast Feeding / Q000009:adverse effects; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006678:HIV / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008895:Milk, Human / Q000821:virology*; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D019562:Viral Load
D019380:Anti-HIV Agents; D019829:Nevirapine