Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age
Department of Pediatrics; Program in Molecular Medicine
Medical Subject Headings
Antiretroviral Therapy, Highly Active; CD4-Positive T-Lymphocytes; Disease Reservoirs; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Infant; Lopinavir; Male; Ritonavir; Treatment Outcome; Viral Load; Virus Latency; Virus Replication
Immunology and Infectious Disease | Pediatrics | Virus Diseases
OBJECTIVES: Identification of HIV infection in exposed infants facilitates early therapy, which may limit viral reservoirs that maintain HIV infection under HAART.
METHODS: The dynamics of the resting CD4 T-cell latent HIV reservoir was determined over the first 2 years of life in 17 HIV-infected infants initiating lopinavir/ritonavir-based HAART at a median age of 8.1 weeks and achieving adequate suppression of plasma viral load by 24 weeks.
RESULTS: The resting CD4 T-cell latent HIV reservoir was detected in 12 of 14 (86%) infants tested at 24 weeks of HAART [median frequency 1.88 infectious units per million (IUPM); range <0.22 to 3.25) in six of 10 (60%) children retested at 96 weeks. The reservoir declined, from 24 to 96 weeks of HAART, at an estimated mean rate of 0.028 log10 IUPM/month, corresponding to a half-life of 11 months (95% confidence interval 6-30 months]. A strong relationship was found between the frequency of latently infected CD4 T cells at 96 weeks of HAART and time to first undetectable plasma viral load (Spearman r = 0.91, P < 0.001).
CONCLUSION: Although the resting CD4 T-cell latent reservoir remains detectable over the first 2 years of HAART in a substantial proportion of infants, its size is associated with time to first undetectable viral load. To minimize HIV reservoirs in infants, rapid curtailment of viremia may limit HIV reservoirs and should be a therapeutic goal of early HAART in infants.
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Citation: AIDS. 2012 Jul 31;26(12):1483-90. doi: 10.1097/QAD.0b013e3283553638.
Persaud, Deborah; Palumbo, Paul E.; Ziemniak, Carrie; Hughes, Michael D.; Alvero, Carmelita G.; Luzuriaga, Katherine; Yogev, Ram; Capparelli, Edmund V.; and Chadwick, Ellen Gould, "Dynamics of the resting CD4(+) T-cell latent HIV reservoir in infants initiating HAART less than 6 months of age" (2012). Pediatric Publications and Presentations. 35.