Antiviral Responses to NNRTI-Based vs. PI-Based ARV Therapy in HIV Infected Infants Who Have or Have Not Received Single Dose NVP for Prevention of Mother-to-Child Transmission of HIV
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: Lamivudine; Lopinavir/ritonavir; Nevirapine; Zidovudine
Intervention description: 4 mg/kg twice daily; 16/4 mg/kg twice daily for participants 2 months of age to less than 6 months of age; 12/3 mg/kg twice daily for participants at least 6 months of age and weighing less than 15 kg; 10/2.5 mg/kg twice daily for participants at least 6 months of age and weighing between 15 kg and 40kg; 400/100 mg twice daily for participants weighing more than 40 kg; Initially: 4 mg/kg for 14 days, then 7 mg/kg twice daily. In protocol version 2.0, Letter of Amendment 1 (September 2007), NVP dose increased to conform with WHO guidelines to: 160 to 200 mg/m^2/dose to max 200 mg once daily for 14 days, then 160 to 200 mg/m^2/dose to max 200 mg twice daily; 180 mg/m^2 twice daily
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine; Nevirapine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 452.0
Sex: All
Minimum age: 2 Months
Maximum age: 36 Months
Healthy volunteers: No
Keywords: Treatment Naive; Mother-To-Child Transmission; MTCT; Pediatrics; Viral resistance

Summary:

      A single dose of nevirapine (SD NVP) given to an HIV infected pregnant woman followed by a
      single dose to her infant has been shown to be an effective way of reducing the risk of
      mother-to-child transmission (MTCT) of HIV. The purpose of this study was to compare the
      effectiveness of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based
      antiretroviral regimen versus a protease inhibitor (PI)-based regimen in HIV infected infants
      who had or had not been exposed to SD NVP for prevention of MTCT.

      >>

      >> A five year follow up has been added to the study.
    

Eligibility criteria:

        Inclusion Criteria for All Participants:>>

          -  age >=6 months to < 36 months (decreased to 2 months in protocol version 4.0)>>

          -  HIV infected>>

          -  Viral load greater than 5,000 copies/ml within 60 days of study entry>>

          -  Treatment naive except for antiretrovirals (ARV) used to prevent MTCT (infant ARV use
             for <=1 week postpartum for prevention of MTCT allowed) >>

          -  Eligible for treatment according to WHO pediatric algorithm (updated in protocol
             version 1.0, Letter of amendment (LOA)#1) and protocol version 2.0, LOA#3). Subjects
             with active opportunistic infections were not eligible for study participation until
             they had been treated and were clinically stable >>

          -  Parent or legal guardian willing to provide signed informed consent>>

        Inclusion Criteria for Cohort I:>>

          -  Documentation of maternal or infant NVP exposure or a highly reliable verbal report.
             (Updated in protocol version 2.0, LOA#3 to require written clinic/hospital
             documentation of infant exposure to SD NVP)>>

          -  Use of maternal ARV, including NVP, permitted during pregnancy>>

          -  One or more of the following: strict formula feeding, initial infant HIV diagnosis
             occurring while younger than 60 days of age, or an initial AIDS-defining illness
             diagnosis by WHO criteria while younger than 60 days of age. >>

        Inclusion Criteria for Cohort II:>>

          -  Use of maternal ARVs, excluding NNRTIs, permitted during pregnancy>>

          -  Evidence of lack of prior NVP exposure (added in protocol version 2.0, LOA#3) by
             review of maternal and child medical records or health card (or other written
             documentation) for evidence of NVP exposure to mother or infant during pregnancy,
             labor, and delivery. If no written documentation showing lack of NVP use was shown in
             these records or if these records were not available for review, then a verbal report
             considered to be highly reliable by the study nurse was acceptable AND one or more of
             the following: >>

               1. Study subject born before single dose NVP was available for prevention of MTCT of
                  HIV in the location of birth of study subject>>

               2. Study subject born before the biological mother's first positive HIV test>>

               3. Site staff had another reason to believe the subject had not been exposed to NVP
                  >> >> Exclusion Criteria for All Participants:>>

          -  Grade 2 or higher aspartate aminotransferase (AST) or alanine aminotransferase (ALT)
             at study screening>>

          -  Grade 3 or higher laboratory toxicity at study screening>>

          -  Received ARVs for anything other than the prevention of intrapartum MTCT. Infants who
             received ARVs after the first week of life (e.g., for the prevention of MTCT of HIV
             through breastfeeding) were excluded >>

          -  Acute serious infections requiring active treatment. Subjects could be receiving
             treatment for active TB if it did not include rifamycin drugs>>

          -  Receiving chemotherapy for an active tumor>>

          -  History of a cardiac conduction abnormality and underlying structural heart disease>>

          -  Required certain medications>> >> Exclusion Criteria for Cohort I: >>

          -  History of or currently breastfeeding. Breastfed infants with a positive HIV test or
             who had experienced an AIDS-defining illness by WHO criteria at 60 days of age or
             younger were not excluded>>

        Exclusion Criteria for Cohort II:>>

          -  Exposure to any maternal NVP or other NNRTI prior to or during the pregnancy or while
             breastfeeding>>

          -  Exposure of infant to NVP at any time including during the first week of life