Trial Information

Optimizing Pediatric HIV-1 Treatment, Nairobi, Kenya (0-4.5 Month RCT)

Hypothesis: Deferring antiretroviral therapy in infants who have immune reconstitution and
adequate growth following early therapy of primary infection (initiated HAART during primary
infection at less than 13 months of age) will not compromise clinical status or growth and
may spare antiretroviral toxicity.

Specific Aim/Primary Objective: To compare growth and morbidity in infants (who initiated
HAART during primary infection at less than or equal to 13 months of age with subsequently
normalized CD4% and growth following 24 months of HAART) randomized to deferred versus
continuous therapy and followed for an additional 18 months.

Secondary Aim/Secondary Objective: To determine predictors of non-progression of HIV among
the infants, including: age, adherence, HIV-1 specific immune responses, baseline HIV-1 RNA,
CD4 percent and immune activation.

Design: Randomized clinical trial involving HIV-1 treatment of infants (<13 months old) for
24 months, followed by randomization and 18 months follow-up of children randomized to
continued versus deferred treatment. This trial is unblinded.

Population: HIV-1 infected infants (<13 months) newly initiating HAART and HIV-1 infected
infants already receiving HAART who initiated HAART at age <13 months will be enrolled.
After 24 months of treatment follow-up, children with CD4% > 25% and normalized growth will
be retained in the study and randomized.

Sample size: 150 infants will be enrolled of which 100 are expected to be eligible for
randomization (50 in each arm).

Treatment: All infants will be treated with HAART according to WHO and Kenyan national
guidelines. The specific regimens that will be used as a part of this study are:

First line regimen

- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)

- d4T/3TC/NVP (stavudine/lamivudine/nevirapine)

- AZT/3TC/ABC (zidovudine/lamivudine/abacavir)

- d4T/3TC/ABC (stavudine/lamivudine/abacavir)

- ABC/3TC/NVP (abacavir/lamivudine/nevirapine)

Second line regimen

- ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir (Kaletra))

For infants with prior exposure to nevirapine as part of PMTCT:

First line regimen - AZT/3TC/LPV/r (zidovudine/lamivudine/lopinavir-ritonavir (kaletra))

Second line regimen

- ABC/ddI or TDF/NVP or EFV (abacavir/didanosine or tenofovir/nevirapine or efavirenz)