Early clinical and immune response to NNRTI-based antiretroviral therapy among women with prior exposure to single-dose nevirapine.
OBJECTIVE
To determine whether prior exposure to single-dose nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) is associated with attenuated CD4 cell response, death, or clinical treatment failure in women starting antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTI).


METHODS
Open cohort evaluation of outcomes for women in program sites across Zambia. HIV treatment was provided according to Zambian/World Health Organization guidelines.


RESULTS
Peripartum NVP exposure status was known for 6740 women initiating NNRTI-containing ART, of whom 751 (11%) reported prior use of NVP for PMTCT. There was no significant difference in mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60) months. Multivariable analyses showed no significant differences in mortality [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of recent NVP exposure with remote exposure suggested a less favorable CD4 cell response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215 cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI, 0.9-2.7).


CONCLUSIONS
Exposure to maternal single-dose NVP was not associated with substantially different short-term treatment outcomes. However, evidence was suggestive that exposure within 6 months of ART initiation may be a risk factor for poor treatment outcomes, highlighting the importance of ART screening and initiation early in pregnancy.
Chi
Benjamin H
BH
Centre for Infectious Disease Research in Zambia, Zambia. bchi@cidrz.org
Sinkala
Moses
M
Stringer
Elizabeth M
EM
Cantrell
Ronald A
RA
Mtonga
Velepi
V
Bulterys
Marc
M
Zulu
Isaac
I
Kankasa
Chipepo
C
Wilfert
Catherine
C
Weidle
Paul J
PJ
Vermund
Sten H
SH
Stringer
Jeffrey S A
JS
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D019829:Nevirapine / Q000008:administration & dosage*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine