Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral therapy may pose a diagnostic challenge

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.

Figure

Infants who had assay detectable cell associated HIV-1 DNA before or at treatment initiation were included. As only dried blood samples (DBS) were available from pre-treatment, which contain cells other than peripheral blood mononuclear cells (PBMC), HIV-1 cell associated DNA results shown in this figure were all from PBMCs collected after treatment initiation. HIV-1 DNA (black circles) copies/million cells and plasma HIV-1 RNA (grey triangles) copies/mL were assessed in 11 patients. “S” denotes those suppressed and “V” those viremic. Open icons indicate HIV-1 DNA or plasma RNA below the limit of detection: plasma HIV-1 RNA was censored at < 100 copies per mL and HIV-1 DNA loads at < 3 copies/million peripheral blood mononuclear cells (PBMCs). All suppressed infants except S6 reached an HIV-1 DNA level < 10 copies/million PBMCs. S9 had HIV-1 DNA declining to undetectable at 3.5 months. The decay slope of suppressed individuals had a conditional R² (95% CI) of 0.77(0.53–0.91); Mean t ½ (95% CI): 64.8 (47.9–105.7) days. V3 had a visit at 1.5 months on ART for which no blood sample was received, thereafter at 3.8 months HIV-1 DNA was undetectable. V5 had undetectable HIV-1 DNA at the first on-ART visit but had viremia detected subsequently. HIV-1 DNA levels increased in V1 and V5.