Anti-HIV Drugs for Treating Infants Who Acquired HIV Infection at Birth
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to compare the effects of anti-HIV drug courses of different
      lengths in infants who became HIV infected at birth.
    

Detailed description: 
      In South Africa, an estimated 250,000 infants are born to HIV-infected mothers each year. A
      high percentage of perinatal HIV infections are due to inadequate or absent mother-to-child
      transmission prophylaxis. Unfortunately, even with optimal prophylaxis, relatively large
      numbers of HIV-infected infants will continue to be born and will require antiretroviral
      therapy (ART). Determining the appropriate times for initiating and interrupting treatment to
      benefit long-term prognosis in infants is a significant health challenge. Evidence suggests
      that starting ART early during acute infection will provide long-term benefits. However,
      longer duration of treatment increases the chance of developing drug-resistant virus, and
      continuous therapy begun early leads to long-term complications in children. This study will
      evaluate the efficacy of two different short-course ART strategies in HIV-infected infants
      from South Africa.

      This study will last at least 3.5 years. There are two parts to this study. In Part A,
      infants with a baseline CD4 percentage (CD4%) of at least 25% and HIV infection diagnosed
      between 6 and 12 weeks of age will be randomly assigned to one of two treatment strategy
      arms. Arm 2 infants will receive ART for approximately 40 weeks until their first birthday.
      Arm 3 infants will receive ART for approximately 96 weeks until their second birthday.
      Treatment in both arms of Part A will begin with first-line, continuous treatment of
      zidovudine, lamivudine, and lopinavir/ritonavir. Those who were initially deferred treatment
      in Arm 1 will be reassessed for initiation of first-line, continuous ART.

      First-line ART will be started in Arm 1 or restarted after interruption in Arms 2 and 3 if
      the appropriate criteria as defined in the protocol is met. First-line treatment of
      zidovudine, lamivudine, and lopinavir/ritonavir will continue until infants reach a study
      endpoint; when this occurs, infants will then change to second-line therapy. Second-line ART
      will consist of didanosine, abacavir sulfate, nevirapine and efavirenz.

      All the primary efficacy analysis for this study will focus on the children enrolled in the
      first phase of Part A (n=377) as proposed by the data safety and monitoring board.

      Follow-up visits will take place for 3.5 to 5 years, depending on time of enrollment. All
      infants will receive routine immunizations and cotrimoxazole (sulfamethoxazole/trimethoprim)
      prophylaxis from age 6 weeks until Week 40. Study visits will occur at study entry, Weeks 2,
      4, 8, 12, 16, 20, 24, 32, 40, and 48; and every 12 weeks thereafter. At these visits, infants
      will have vital sign measurements, a physical exam, and a medical history evaluation. Blood
      and urine collection will occur at all study visits. Infants' parents or guardians will also
      be asked to complete an adherence questionnaire.

      Participants enrolled in CIPRA-ZA Project 2 are encouraged to enroll in an observational
      substudy organized by the Wistar Institute (Dr. Luis Montaner, Principal Investigator), in
      conjunction with the CIPRA team. This study is entitled,"Pediatric Immune Correlates of Early
      Anti-HIV Therapy." The goal of this 5-year substudy is to evaluate 120 HIV infected children
      from the parent study twice a year and compare them to HIV uninfected age-matched controls.
      Children will be evaluated by (a) characterization and identification of the innate and
      adaptive immune reconstitution outcomes of early (9 or 21 months) therapy in infants infected
      with HIV at birth and (b) identification of immune correlate outcomes to clinical progression
      within a period of 2 to 3 years of follow-up after stopping therapy.
    

Intervention name(s): Abacavir sulfate; Didanosine; Efavirenz; Lamivudine; Lopinavir/Ritonavir; Nevirapine; Zidovudine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.; Second Line Regimen: Either 100 mg/m^2 or 120 mg/m^2 taken orally twice daily. Dosage depends on age. Guidelines for switching from first line to second line therapy are available in the protocol.; Second Line Regimen: taken orally once daily. Dosage depends on weight. Guidelines for switching from first line to second line therapy are available in the protocol.; First Line Regimen: 4 mg/kg taken orally twice daily; First Line Regimen: taken orally twice daily. Dosage depends on age and weight.; Second Line Regimen: 150 - 200 mg/m^2 taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol.; First Line Regimen: 240 mg/m^2 taken orally twice daily
Other intervention name(s): ABC; Ziagen; ddI; Videx; EFV; Stocrin; 3TC; Epivir; LPV/r; Kaletra; NVP; Viramune; AZT; Retrovir
Intervention MeSH terms: Ritonavir; Lopinavir; Lamivudine; Zidovudine; Nevirapine; Abacavir; Didanosine; Efavirenz
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study had two parts: Part A where children were enrolled with CD4% ≥ 25% and Part B where children were enrolled with CD4% < 25%. Part A had three arms: ART-Deferred, ART-40W and ART-96W where ART-40W and ART-96W were the early therapy arms for 40 and 96 weeks respectively. Part B were enrolled into two Arms: ART-40W and ART-96W. The primary efficacy analysis for CHER was based on 377 children that were enrolled in Part A in the first phase of the study. The NIH African data safety and monitoring board recommended that primary analysis be focussed on 377 children enrolled in the first phase of Part A. Additionally, all the key manuscripts have been analysed using this group. Hence all the results presented in clinicaltrials.gov will be specific to this group with three arms.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Infant; Perinatal; HIV; Disease Transmission, Vertical; Anti-Retroviral Agents; Treatment Interruption; Treatment Naive; Acute Infection; Mother-to-Child Transmission