Analysis of nevirapine resistance in HIV-infected infants who received extended nevirapine or nevirapine/zidovudine prophylaxis

Department of Pathology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
AIDS (London, England) (Impact Factor: 5.55). 04/2011; 25(7):911-7. DOI: 10.1097/QAD.0b013e328344fedc
Source: PubMed


In the Post Exposure Prophylaxis of Infants (PEPI)-Malawi trial, infants received up to 14 weeks of extended nevirapine (NVP) or extended NVP with zidovudine (NVP + ZDV) to prevent postnatal HIV transmission. We examined emergence and persistence of NVP resistance in HIV-infected infants who received these regimens prior to HIV diagnosis.
Infant plasma samples collected at 14 weeks of age were tested using the ViroSeq HIV Genotyping System and a sensitive point mutation assay, LigAmp (for K103N and Y181C). Samples collected at 6 and 12 months of age were analyzed using LigAmp.
At 14 weeks of age, NVP resistance was detected in samples from 82 (75.9%) of 108 HIV-infected infants. Although the frequency of NVP resistance detected by ViroSeq was lower in the extended NVP + ZDV arm than in the extended NVP arm, the difference was not statistically significant (38/55 = 69.1% vs. 44/53 = 83.0%, P = 0.12). Similar results were obtained using LigAmp. Using LigAmp, the proportion of infants who still had detectable NVP resistance at 6 and 12 months was similar among infants in the two study arms (at 6 months: 17/20 = 85.0% for extended NVP vs. 21/26 = 80.8% for extended NVP + ZDV, P = 1.00; at 12 months: 9/16 = 56.3% for extended NVP vs.10/13 = 76.9% for extended NVP + ZDV, P = 0.43).
Infants exposed to extended NVP or extended NVP + ZDV had high rates of NVP resistance at 14 weeks of age, and resistant variants frequently persisted for 6-12 months. Frequency and persistence of NVP resistance did not differ significantly among infants who received extended NVP only vs. extended NVP + ZDV prophylaxis.

Download full-text


Available from: Jessica Fogel,

  • AIDS (London, England) 04/2011; 25(7):997-9. DOI:10.1097/QAD.0b013e3283463d44 · 5.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The HIV epidemic in higher-income nations is driven by receptive anal intercourse, injection drug use through needle/syringe sharing, and, less efficiently, vaginal intercourse. Alcohol and noninjecting drug use increase sexual HIV vulnerability. Appropriate diagnostic screening has nearly eliminated blood/blood product-related transmissions and, with antiretroviral therapy, has reduced mother-to-child transmission radically. Affected subgroups have changed over time (e.g., increasing numbers of Black and minority ethnic men who have sex with men). Molecular phylogenetic approaches have established historical links between HIV strains from central Africa to those in the United States and thence to Europe. However, Europe did not just receive virus from the United States, as it was also imported from Africa directly. Initial introductions led to epidemics in different risk groups in Western Europe distinguished by viral clades/sequences, and likewise, more recent explosive epidemics linked to injection drug use in Eastern Europe are associated with specific strains. Recent developments in phylodynamic approaches have made it possible to obtain estimates of sequence evolution rates and network parameters for epidemics.
    Cold Spring Harbor Perspectives in Medicine 05/2012; 2(5):a007195. DOI:10.1101/cshperspect.a007195 · 9.47 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The HIV Prevention Trials Network (HPTN) 046 trial evaluated the efficacy of extended infant nevirapine (NVP) administration for prevention of HIV transmission through breastfeeding. Infants received daily NVP up to 6 weeks of age. HIV-uninfected infants (the intent-to-treat group) received daily NVP or placebo up to 6 months of age. We analyzed emergence of NVP resistance in infants who acquired HIV infection despite prophylaxis. Methods: HIV genotyping was performed using the ViroSeq HIV Genotyping System. Medians and proportions were used to summarize data. Two-sided Fisher exact tests were used to evaluate associations between categorical variables. Results: NVP resistance was detected in 12 (92.3%) of 13 infants who were HIV-infected by 6 weeks and in 7 (28%) of 25 infants who were HIV-uninfected at 6 weeks and HIV-infected at 6 months of age (6/8 = 75% in the NVP arm, 1/17 = 5.9% in the placebo arm, P = 0.001). Among those 25 infants, 4 had mothers who initiated an antiretroviral treatment regimen by 6 months postpartum. In all 4 cases, the treatment regimen included a non-nucleoside reverse transcriptase inhibitor (NVP or efavirenz). NVP resistance was detected in all 4 of those infants by 6 months of age (4/4 = 100%). In contrast, only 3 (14.2%) of the remaining 21 HIV-infected infants whose mothers did not initiate antiretroviral treatment developed NVP resistance (P = 0.003). Conclusions: Extended NVP prophylaxis significantly increased the risk of NVP resistance in infants who acquired HIV infection after 6 weeks of age. Treatment of maternal HIV infection was also associated with emergence of NVP resistance in HIV-infected, breastfed infants.
    The Pediatric Infectious Disease Journal 12/2012; 32(4). DOI:10.1097/INF.0b013e31827f44ee · 2.72 Impact Factor
Show more