Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis.
BACKGROUND
Single-dose nevirapine (NVP) is the main option for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in countries with limited resources. However, the use of single-dose NVP results in HIV-1 viral resistance which could compromise the success of subsequent treatment of mother and child with antiretroviral combinations that include non-nucleosidic-reverse-transcriptase inhibitors. This systematic review and meta-analysis of summarized data aimed to estimate the proportion of mothers and children with NVP resistance mutations detected in plasma samples 4-8 weeks postpartum after single-dose NVP use for PMTCT.


METHODS
Systematic search of electronic databases (MEDLINE, PASCAL) and conference proceedings (1997 to February 2006). Inclusion of all studies, without design, place or language restrictions, meeting the following criteria: use of single-dose NVP; viral genotyping performed with standard sequence analyses, between 4 and 8 weeks postpartum, in plasma samples; available public report; report of mothers' median baseline plasma HIV-1 RNA levels. Data extraction by two independent reviewers using a standardized form created for this purpose. Logistic random effect models to obtain pooled estimates. Univariable and multivariable meta-regression to explore sources of heterogeneity.


RESULTS
The pooled estimate of NVP resistance prevalence was 35.7% [95% confidence interval (CI) 23.0-50.6] in women in 10 study arms using single-dose NVP +/- other antepartum antiretrovirals and 4.5% (CI 2.1-9.4) in three study arms providing also postpartum antiretrovirals (adjusted odds ratio 0.08; CI 0.04-0.16). The corresponding estimates in children were 52.6% (CI 37.7-67.0) in seven study arms using single-dose NVP only and 16.5% (CI 8.9-28.3) in eight study arms combining single-dose NVP with other antiretrovirals.


CONCLUSIONS
Single-dose NVP is widely used for PMTCT in resource-poor settings, but the burden of viral resistance is high in both women and children. It is substantially lower in studies providing additional postpartum antiretrovirals. The clinical implications of these findings should be further investigated.
Arrivé
Elise
E
Unité INSERM 593, Bordeaux, France. Elise.arrive@isped.u-bordeaux2.fr
Newell
Marie-Louise
ML
Ekouevi
Didier K
DK
Chaix
Marie-Laure
ML
Thiebaut
Rodolphe
R
Masquelier
Bernard
B
Leroy
Valériane
V
Perre
Philippe Van de
PV
Rouzioux
Christine
C
Dabis
François
F
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D019829:Nevirapine / Q000627:therapeutic use*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine