Kirsten A Veldsman1, Jean Maritz1,2, Shahieda Isaacs1, Mary G Katusiime1, Anita Janse van Rensburg3,4, Barbara Laughton3,4, John W Mellors5, Mark F Cotton3,4, Gert U van Zyl1,2. 1. Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town. 2. National Health Laboratory Service, Cape Town. 3. Department Paediatrics and Child Health, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town. 4. Tygerberg Children's Hospital, Cape Town, South Africa. 5. Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract
OBJECTIVE: Birth diagnosis of HIV-1 infection offers an ideal opportunity for early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit disease progression. Although data on cellular HIV-1 DNA decay exist for children commencing treatment from 2 to 3 months of age, data are lacking for starting shortly after birth. DESIGN: We studied infants who initiated ART within 8 days after birth to assess HIV-1 DNA levels longitudinally. METHODS: Children were recruited from public health clinics in Cape Town where birth diagnosis of HIV-1 coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were determined using a sensitive quantitative PCR targeting a conserved region in integrase. RESULTS: Of 11 infants diagnosed and beginning ART within 8 days of birth with detectable pre-ART HIV-1 DNA, three subsequently had undetectable HIV-1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven who had virologic suppression (defined as a continuous downward trend in plasma HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9-105.7)]. CONCLUSION: In infants initiated on ART within 8 days of life the combination of maternal ART, and early ART for prophylaxis and treatment contribute to rapid decline of HIV-1 infected cells to low or undetectable levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive diagnosis when confirmatory testing is delayed.
OBJECTIVE: Birth diagnosis of HIV-1 infection offers an ideal opportunity for early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit disease progression. Although data on cellular HIV-1 DNA decay exist for children commencing treatment from 2 to 3 months of age, data are lacking for starting shortly after birth. DESIGN: We studied infants who initiated ART within 8 days after birth to assess HIV-1 DNA levels longitudinally. METHODS:Children were recruited from public health clinics in Cape Town where birth diagnosis of HIV-1 coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were determined using a sensitive quantitative PCR targeting a conserved region in integrase. RESULTS: Of 11 infants diagnosed and beginning ART within 8 days of birth with detectable pre-ARTHIV-1 DNA, three subsequently had undetectable HIV-1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven who had virologic suppression (defined as a continuous downward trend in plasma HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9-105.7)]. CONCLUSION: In infants initiated on ART within 8 days of life the combination of maternal ART, and early ART for prophylaxis and treatment contribute to rapid decline of HIV-1 infected cells to low or undetectable levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive diagnosis when confirmatory testing is delayed.
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