Response to antiretroviral therapy after a single, peripartum dose of nevirapine.
BACKGROUND
A single dose of nevirapine during labor reduces perinatal transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to viral nevirapine resistance mutations in mothers and infants.


METHODS
We studied the response to nevirapine-based antiretroviral treatment among women and infants who had previously been randomly assigned to a single, peripartum dose of nevirapine or placebo in a trial in Botswana involving the prevention of the transmission of HIV-1 from mother to child. All women were treated with antenatal zidovudine. The primary end point for mothers and infants was virologic failure by the 6-month visit after initiation of antiretroviral treatment, estimated within groups by the Kaplan-Meier method.


RESULTS
Of 218 women who started antiretroviral treatment, 112 had received a single dose of nevirapine and 106 had received placebo. By the 6-month visit after the initiation of antiretroviral treatment, 5.0% of the women who had received placebo had virologic failure, as compared with 18.4% of those who had received a single dose of nevirapine (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after receiving placebo or a single dose of nevirapine, no women in the placebo group and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast, virologic failure rates did not differ significantly between the placebo group and the nevirapine group among 158 women starting antiretroviral treatment 6 months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants also began antiretroviral treatment (15 in the placebo group and 15 in the nevirapine group). Virologic failure by the 6-month visit occurred in significantly more infants who had received a single dose of nevirapine than in infants who had received placebo (P<0.001). Maternal and infant findings did not change qualitatively by 12 and 24 months after the initiation of antiretroviral treatment.


CONCLUSIONS
Women who received a single dose of nevirapine to prevent perinatal transmission of HIV-1 had higher rates of virologic failure with subsequent nevirapine-based antiretroviral therapy than did women without previous exposure to nevirapine. However, this applied only when nevirapine-based antiretroviral therapy was initiated within 6 months after receipt of a single, peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587 [ClinicalTrials.gov].).
Lockman
Shahin
S
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA. slockman@hsph.harvard.edu
Shapiro
Roger L
RL
Smeaton
Laura M
LM
Wester
Carolyn
C
Thior
Ibou
I
Stevens
Lisa
L
Chand
Fatima
F
Makhema
Joseph
J
Moffat
Claire
C
Asmelash
Aida
A
Ndase
Patrick
P
Arimi
Peter
P
van Widenfelt
Erik
E
Mazhani
Loeto
L
Novitsky
Vladimir
V
Lagakos
Stephen
S
Essex
Max
M
D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D053208:Kaplan-Meier Estimate; D007743:Labor, Obstetric; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011263:Pregnancy Trimester, Third; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D015215:Zidovudine; D019829:Nevirapine