Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine); d4T/3TC/NVP (stavudine/lamivudine/nevirapine); AZT/3TC/ABC (zidovudine/lamivudine/abacavir); d4T/3TC/ABC (stavudine/lamivudine/abacavir); ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir); ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz); ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
Intervention description: First line regimen; First line regimen; First line regimen; First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.; Second line regimen; Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.; First line regimen
Intervention MeSH terms: Ritonavir; Lopinavir; Tenofovir; Lamivudine; Zidovudine; Nevirapine; Abacavir; Stavudine; Didanosine; Efavirenz; Dideoxynucleosides
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 6 Months
Maximum age: 18 Months
Healthy volunteers: No
Keywords: HIV-1; Pediatric; nevirapine; HAART; Resistance; Treatment Naive

Summary:

      Globally, children who acquire HIV-1 increasingly do so in the context of maternal
      antiretroviral prophylaxis. It is important to determine whether maternal antiretroviral
      prophylaxis should alter infant treatment regimens. Nevirapine (NVP) is commonly used for
      PMTCT and is also a commonly used first-line drug for treatment of pediatric HIV-1.
      Approximately half of infants exposed to NVP have detectable NVP resistance early in infancy,
      with loss of detectable resistance over time. Thus, if an HIV-1 infected child was exposed to
      single-dose NVP prophylaxis, the question remains whether NVP or any NNRTI can be used
      effectively in therapeutic regimens. Alternative PI-based regimens are associated with
      heat-lability, poor palatability, cumulative toxicity, and fewer salvage options. This poses
      challenges for pediatric PI-based highly active antiretroviral therapy (HAART) in settings
      without refrigeration and limited antiretroviral repertoire. It is plausible that in older
      NVP-exposed infants (older than 6 months since exposure) who are genotypically
      NVP-susceptible, that nevirapine will be effective and useful.

      We propose to study resistance in a pediatric HIV-1 clinical trial involving 100 children.
      Among children enrolled at between 6 and 18 months of age, we will provide real-time
      field-based genotypic NVP-resistance testing, and randomize 100 NVP-susceptible children to
      NVP-containing versus NVP-sparing HAART to compare therapeutic response, adverse events, and
      morbidity in the 2 arms during 2-year follow-up. Follow-up in these studies will be closely
      monitored by an external Data Safety and Monitoring Board (DSMB).
    

Eligibility criteria:

        Inclusion Criteria:

          -  6-18 months age

          -  HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)

          -  Mother exposed to NVP-containing PMTCT regimen during currently ended pregnancy and/or
             infant received NVP-containing PMTCT regimen

          -  Infant susceptible to NVP (i.e. no detectable NVP resistance on genotypic testing)

          -  Caregiver of infant plans to reside in Nairobi for at least 3 years

          -  Caregiver is able to provide sufficient location information

        Exclusion Criteria:

          -  Infant has received any prior antiretroviral therapy (expect prophylaxis for PMTCT)

          -  Infant has evidence of active tuberculosis

          -  Mother currently receiving NVP-containing HAART and breastfeeding the infant