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RAPID DECLINE OF TOTAL HIV DNA IN CHILDREN STARTING ART WITHIN 8 DAYS OF BIRTH
Kirsten A. Veldsman1, Jean Maritz2, Shahieda Isaacs1, Mary Grace K .Katusiime1, Heleen la Grange1, Anita Janse van Rensburg1, Barbara Laughton2, John Mellors3, Mark Cotton2, Gert U. van Zyl1
1Stellenbosch Univ, Parow, South Africa,2Stellenbosch Univ, Cape Town, South Africa,3Univ of Pittsburgh, Pittsburgh, PA, USA
Early infant antiretroviral combination therapy (ART), initiated in the first 2 months of life, reduces HIV-1 infected and transcriptionally active cells (van Zyl, JID 2015). In the case of the Mississippi baby, very early ART, initiated shortly after birth, resulted in delayed viral rebound after therapy interruption, probably due to a very small pool of infected cells. Although there are reports from resource rich settings of undetectable or very low levels of HIV DNA in children who started ART shortly after birth, data from resource limited settings are very limited.
Eleven children diagnosed (at least 2 positive HIV nucleic acid tests) through a public health sector birth diagnosis program were initiated on ART between 0 and 8 days after birth (median 3 days). Peripheral blood mononuclear cells (PBMCs) and plasma were processed at 3 monthly visits. HIV-1 total DNA was measured with a sensitive quantitative PCR assay (Hong, JCM 2016), adapted for HIV-1 subtype C, targeting a conserved region in HIV-1 integrase (iCAD; limit of detection 3 copies/million cells). Plasma HIV-1 RNA was quantified by Roche COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 v2.
The initial ART regimen consisted of AZT/3TC/NVP, with NVP replaced by LPV/r after 2 weeks of age. Median baseline plasma HIV-1 RNA was 4.0 (range 2.4-4.7) log10 copies/ml. One child had ongoing viremia. All other children achieved plasma HIV-1 RNA <100 copies/ml after a median of 4 months, but two had subsequent single viremic episodes. Four children had no detectable HIV-1 DNA in ≥ 500,000 PBMCs assayed when first sampled at 9 days, 3.8 months, 4.9 months and 8.2 months after starting ART. Stored dried blood spots from before ART initiation were found for 3 of these children: 2 had detectable HIV-1 DNA by iCAD and one child with a low baseline plasma HIV-1 RNA load of 265 copies/mL had undetectable iCAD. In the other 6 children, excluding the child with ongoing viremia, there was progressive decline in HIV-1 DNA with 4 of 6 reaching < 10 copies per million cells within 13 months of ART initiation.
Early ART initiation within a few days of birth can suppress viral replication, limit the initial number of HIV infected cells and result in their subsequent decay to undetectable levels. However, this rapid decay and limited sample amount require more robust HIV-1 molecular diagnostics to detect HIV persistence on ART and to prevent misdiagnosis of HIV infection in uninfected children.