Clinical trial NCT00102960
Conditions: HIV Infections
Keywords: Infant Perinatal HIV Disease Transmission, Vertical Anti-Retroviral Agents Treatment Interruption Treatment Naive Acute Infection Mother-to-Child Transmission
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2005-07-01; Completion date: 2013-01-01
Enrollment: 377 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: 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.

Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily arm 2: Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2

Abacavir sulfate: 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.

Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily arm 3: Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older.

Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight.

Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: 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.

Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age.

Efavirenz: Second Line, once daily Nevirapine: Second Line, once daily
Interventions: intervention 1: Abacavir sulfate intervention 2: Didanosine intervention 3: Efavirenz intervention 4: Lamivudine intervention 5: Lopinavir/Ritonavir intervention 6: Nevirapine intervention 7: Zidovudine
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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. intervention 4: First Line Regimen: 4 mg/kg taken orally twice daily intervention 5: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. intervention 6: 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. intervention 7: First Line Regimen: 240 mg/m\^2 taken orally twice daily

Protocol documents: