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Ensayos clínicos

Ensayos clínicos

Anti-HIV Drugs for Treating Infants Who Acquired HIV Infection at Birth

Patrocinador(es) del estudio: National Institute of Allergy and Infectious Diseases (NIAID)
Números de identificación: NCT00102960, CIPRA-SA Project 2
  • Concluido

Propósito del estudio

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.

Afección:Fase:
Infecciones por el VIH
Fase 3

Detalles del estudio

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.



In Part B, infants with a baseline CD4% less than 25% will receive 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.



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.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.



In Part B, infants with a baseline CD4% less than 25% will receive 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.



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.

Criterios de inclusión

    for Infants: NOTE: Per Letter of Amendment dated 04/04/07, Part B of this study is no longer recruiting participants. Per Letter of Amendment dated 09/16/08 Arm 1 of this study is longer recruiting.
    • HIV infected
    • Antiretroviral naive. Infants who have previously received antiretroviral drugs used
    to prevent mother-to-child transmission are eligible for the study.
    • Parent or legal guardian willing to provide informed consent and comply with study requirements

Criterios de exclusión

    for Infants:
    • Any major life-threatening congenital abnormalities
    • Severe CDC Stage B or C disease
    • Liver enzyme, absolute neutrophil count, hemoglobin, electrolyte, creatinine, or
    clinical toxicity of Grade 3 or higher at screening
    • Any acute or clinically significant medical event that would preclude participation in
    the study. Randomization can take place as soon as the incurrent illness has resolved if the child is still less than or equal to 12 weeks of age.
    • Use of investigational drugs
    • Require certain medications. More information on this criterion can be found in the
    protocol.
    • Inability to tolerate oral medication
    • Birth weight less than 2 kg (4.4 lbs)

Actualizado: 21 de noviembre del 2008

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