Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Little is known about what treatment combinations are best for HIV infected children. This
      study examined the long-term effectiveness of different anti-HIV drug combinations in
      children and strategies for switching treatment if the first treatment does not work. The
      study enrolled children who had not previously taken anti-HIV medication. Participants in
      this study were recruited in the United States, South America and Europe.

      Some European children may also enroll in a substudy that will observe changes in body fat in
      children taking anti-HIV medications.
    

Detailed description: 
      Antiretroviral therapy in children aims to prolong clinical and immunologic health.
      Currently, there are no data defining a particular highly active antiretroviral therapy
      (HAART) strategy as the optimal first-line therapy for children. This study evaluated the
      long-term efficacy of two HAART regimens used as initial therapy: 1) two nucleoside reverse
      transcriptase inhibitors (NRTIs) plus a protease inhibitor (PI), and 2) two NRTIs plus a
      nonnucleoside reverse transcriptase inhibitor (NNRTI). It also evaluated different strategies
      for switching therapy when the initial regimen fails. The long-term nature of this study
      should clarify whether early switching of therapy improves immunologic and virologic
      outcomes, or results in a more rapid exhaustion of treatment options. The study was conducted
      in the United States and in Europe.

      Participants in this study had a CD4 cell count and viral load test during a screening visit.
      Participants had an entry visit that included blood and urine tests. Participants were then
      randomly assigned to one of four groups: Groups PI/1K and PI/30K received two NRTIs plus a
      PI; Groups NNRTI/1K and NNRTI/30K received two NRTIs plus an NNRTI. The medications allowed
      in the study were: abacavir, didanosine, emtricitabine, emtricitabine/tenofovir disoproxil
      fumarate, lamivudine, lamivudine/zidovudine, stavudine, tenofovir disoproxil fumarate,
      zalcitabine, and zidovudine (NRTIs); efavirenz and nevirapine (NNRTIs);
      efavirenz/emtricitabine/tenofovir disoproxil fumurate (NNRTI/NRTI); and
      amprenavir,atazanavir, darunavir, fosamprenavir calcium, indinavir, lopinavir/ritonavir,
      nelfinavir, saquinavir, ritonavir, and tipranavir (PIs). Note: Per the 06/28/05 amendment of
      this trial, emtricitabine, emtricitabine/tenofovir disoproxil fumarate, and tenofovir
      dioproxil fumarate were added to the list of medications that could be included in a
      participant's treatment regimen.

      For participants whose initial regimen failed, or who experienced clinical disease
      progression (indicated by the development of a new CDC Category C diagnosis) or other
      clinical disease progression at or after Week 24 of first-line therapy, second-line therapy
      was strongly encouraged. (However, if poor adherence was suspected as a possible reason for
      an increase in HIV viral load, the site and the clinician were to try to improve patient
      adherence and obtain additional confirmatory viral load values within a five-week time
      frame.) In second-line therapy, participants who initially took NRTIs with a PI switched to
      NRTIs and an NNRTI. Participants who initially took NRTIs and an NNRTI switched to NRTIs and
      a PI. The timing of the switch was based on the participant's group: Groups PI/1K and
      NNRTI/1K switched to second-line treatment when viral load was 1,000 copies/ml or greater;
      Groups PI/30K and NNRTI/30K switched to second-line treatment when viral load was 30,000
      copies/ml or greater. Participants who failed second-line therapy discontinued study
      treatment and were offered the best available therapy at the discretion of the clinician.

      Participants had study visits at Weeks 2, 4, 8, 12, 16, 24, and every 12 weeks thereafter
      until the drug regimen was switched to second-line treatment. Participants then had a
      re-entry visit and the schedule of visits restarted. Participants were in the study between 4
      and 7 years, depending on when they enrolled. All study visits included medical history, a
      physical exam, and blood collection. Urine collection occurred at most visits. Participants
      were asked to complete adherence questionnaires and PACTG participants underwent
      neuropsychological assessments at selected visits.

      All participants in this study were encouraged to coenroll in PACTG 219C, Long-Term Effects
      of HIV Exposure and Infection in Children. Participants in the European portion of the study
      may be asked to enroll in a substudy to observe the development and progression of
      lipodystrophy syndrome in children.
    

Intervention name(s): NRTIs (ABC, FTC, FTC/TDF, 3TC, 3TC/AZT, d4T, TDF, ddC, AZT); NNRTIs (EFV, NVP); PIs (AMP, IDV, LPV/r, NFV, SQV, RTV)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Accepted NRTIs: abacavir sulfate (ABC), emtricitabine (FTC), emtricitabine/Tenofovir disoproxil fumarate (FTC/TDF), lamivudine (3TC), lamivudine/zidovudine (3TC/AZT), stavudine (d4T), tenofovir disoproxil fumarate (TDF), zalcitabine (ddC), zidovudine (AZT) Prescribed per participant's doctor; Accepted NNRTIs: efavirenz (EFV), nevirapine (NVP)
Prescribed per participant's doctor; Accepted PIs: amprenavir (APV). indinavir sulfate (IDV), lopinavir/ritonavir (LPV/r), nelfinavir mesylate (NFV), saquinavir (SQV), ritonavir (RTV)
Prescribed per participant's doctor
Other intervention name(s): 2 NRTIs/PI, change@viral load 1000 copies/ml or higher; 2 NRTIs/PI, change@viral load 30,000 copies/ml or higher; 2 NRTIs/NNRTI, change@viral load 1000 copies/ml or higher; 2 NRTIs/NNRTI, change@viral load 30,000 copies/ml or higher; 2 NRTIs/NNRTI, change@viral load 1000 copies/ml or higher; 2 NRTIs/NNRTI, change@viral load 30,000 copies/ml or higher; 2 NRTIs/PI, change@viral load 1000 copies/ml or higher; 2 NRTIs/PI, change@viral load 30,000 copies/ml or higher
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug Therapy, Combination; HIV Protease Inhibitors; Reverse Transcriptase Inhibitors; Viral Load; Treatment Naive