Early antiretroviral therapy and mortality among HIV-infected infants
Avy Violari, Mark F Cotton, Diana M Gibb, Abdel G Babiker, Jan Steyn, Shabir A Madhi, Patrick Jean-Philippe, James A McIntyre, CHER Study Team, A Violari, J McIntyre, W Pelser, J Steyn, S Madhi, A Naeem-Sheik, M Budge, M Saleh, S Cassimjee, E Lazarus, S Mashinini, S Dlamini, V Kemese, J Bolton, M F Cotton, H Rabie, A Janse van Rensburg, E Dobbels, G Fourie, M Bester, W Orange, R Arendze, C Andrea, M Smuts, K Smith, T Louw, A Abrahams, K Kelly, A Bohle, I Mong, J Howard, T Cyster, G Solomon, G Benjamin, J Mkalipi, E Barnes, I Sanne, G Gray, R Panchia, C Davies, M Cornell, W Stevens, D Glencross, S Spector, C van der Horst, A G Babiker, D M Gibb, J-M Steens, W X Snowden, N Thoofer, E Loeliger, E Handelsman, K Reese, P Jean-Phillipe, J Nadler, J McNamara, R Hoff, S Lehrman, C Oster, T Peto, L Levin, D Gibb, S Ellenberg, R DerSimonian, A Dodoo, D Harrington, A Kamali, E Katabira, C Lombard, C Luo, M F Marshall, L Mokgatlhe, A Mwinga, A Nunn, H Saloojee, M Sande, J Schoeman, J Singh, R Boss-Victoria, T Chipato, S Emerson, J Mfutso-Bengo, P Mwaba, Avy Violari, Mark F Cotton, Diana M Gibb, Abdel G Babiker, Jan Steyn, Shabir A Madhi, Patrick Jean-Philippe, James A McIntyre, CHER Study Team, A Violari, J McIntyre, W Pelser, J Steyn, S Madhi, A Naeem-Sheik, M Budge, M Saleh, S Cassimjee, E Lazarus, S Mashinini, S Dlamini, V Kemese, J Bolton, M F Cotton, H Rabie, A Janse van Rensburg, E Dobbels, G Fourie, M Bester, W Orange, R Arendze, C Andrea, M Smuts, K Smith, T Louw, A Abrahams, K Kelly, A Bohle, I Mong, J Howard, T Cyster, G Solomon, G Benjamin, J Mkalipi, E Barnes, I Sanne, G Gray, R Panchia, C Davies, M Cornell, W Stevens, D Glencross, S Spector, C van der Horst, A G Babiker, D M Gibb, J-M Steens, W X Snowden, N Thoofer, E Loeliger, E Handelsman, K Reese, P Jean-Phillipe, J Nadler, J McNamara, R Hoff, S Lehrman, C Oster, T Peto, L Levin, D Gibb, S Ellenberg, R DerSimonian, A Dodoo, D Harrington, A Kamali, E Katabira, C Lombard, C Luo, M F Marshall, L Mokgatlhe, A Mwinga, A Nunn, H Saloojee, M Sande, J Schoeman, J Singh, R Boss-Victoria, T Chipato, S Emerson, J Mfutso-Bengo, P Mwaba
Abstract
Background: In countries with a high seroprevalence of human immunodeficiency virus type 1 (HIV-1), HIV infection contributes significantly to infant mortality. We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy (CHER) trial.
Methods: HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage (the CD4 percentage) of 25% or more were randomly assigned to receive antiretroviral therapy (lopinavir-ritonavir, zidovudine, and lamivudine) when the CD4 percentage decreased to less than 20% (or 25% if the child was younger than 1 year) or clinical criteria were met (the deferred antiretroviral-therapy group) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age (the early antiretroviral-therapy groups). We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy.
Results: At a median age of 7.4 weeks (interquartile range, 6.6 to 8.9) and a CD4 percentage of 35.2% (interquartile range, 29.1 to 41.2), 125 infants were randomly assigned to receive deferred therapy, and 252 infants were randomly assigned to receive early therapy. After a median follow-up of 40 weeks (interquartile range, 24 to 58), antiretroviral therapy was initiated in 66% of infants in the deferred-therapy group. Twenty infants in the deferred-therapy group (16%) died versus 10 infants in the early-therapy groups (4%) (hazard ratio for death, 0.24; 95% confidence interval [CI], 0.11 to 0.51; P<0.001). In 32 infants in the deferred-therapy group (26%) versus 16 infants in the early-therapy groups (6%), disease progressed to Centers for Disease Control and Prevention stage C or severe stage B (hazard ratio for disease progression, 0.25; 95% CI, 0.15 to 0.41; P<0.001). Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant; no drugs were permanently discontinued. After a review by the data and safety monitoring board, the deferred-therapy group was modified, and infants in this group were all reassessed for initiation of antiretroviral therapy.
Conclusions: Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%. (ClinicalTrials.gov number, NCT00102960.)
2008 Massachusetts Medical Society
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Source: PubMed