HIV-1 DNA decay is faster in children who initiate ART shortly after birth than later

Kirsten A Veldsman; Anita Janse van Rensburg; Shahieda Isaacs; Shalena Naidoo; Barbara Laughton; Carl Lombard; Mark F Cotton; John W Mellors; Gert U van Zyl

doi:10.1002/jia2.25368

HIV-1 DNA decay is faster in children who initiate ART shortly after birth than later

J Int AIDS Soc. 2019 Aug;22(8):e25368. doi: 10.1002/jia2.25368.

Authors

Affiliations

¹ Division of Medical Virology, Stellenbosch University, Faculty of Medicine and Health Sciences, Cape Town, South Africa.
² Department Pediatrics and Child Health, Tygerberg Children's Hospital and Family Clinical Research Unit, Stellenbosch University, Cape Town, South Africa.
³ Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁴ Biostatistics Unit, South African Medical Research Council, Cape Town, South Africa.
⁵ Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ National Health Laboratory Service, Cape Town, South Africa.

Abstract

Introduction: There is limited data in children on whether persistence of HIV-1 infected cells is affected by age at initiating antiretroviral therapy (ART), its duration or any subsequent ART interruption. We therefore investigated the effects of both age of ART initiation and duration of ART interruption on HIV-1 DNA decay in children.

Methods: We investigated HIV-1 DNA decay in three groups of children on ART: Group-1 (n = 7) started uninterrupted ART within eight days of life; Group-2 (n = 8) started uninterrupted ART at a median of five months of age; and Group-3 (n = 23) started ART at a median age of 1.8 months for either 40 or 96 weeks, then interrupted ART (median of seven months), and restarted ART based on CD4 count and clinical criteria. Total HIV-1 DNA was assayed using a sensitive HIV-1 subtype C-adapted quantitative PCR for integrase. The duration of ART was square root transformed to fit the observed slowing of HIV-1 DNA decay rate. For each group, point estimates for decay rates were determined after six months of continuous suppressive ART in groups 1 and 2 or six months after restarting ART in Group-3. Groups-2 and 3 were combined using a mixed effect regression model to investigate covariates of HIV-1 DNA decay rate.

Results and discussion: At six months of continuous suppressive ART, the HIV-1 DNA t½ (95% CI) was shorter in Group-1 (n = 7): 2.7 months (2.1 to 3.8), than 9.2 months (7.4 to 12.1) in Group-2 (n = 8); and 9.6 months (7.6 to 12.6) in Group-3 (n = 23) (p < 0.01). In multivariable analyses, HIV-1 DNA before treatment (p < 0.001) and the change in HIV-1 DNA during interruption (p < 0.01) were independent predictors of slower HIV-1 DNA decay.

Conclusions: These data suggest that ART initiation within the first week of life can reduce the persistence of long-lived infected cells. Delaying ART is associated with slower decay of infected cells.

Keywords: Africa; HIV-1 DNA kinetics; HIV-1 persistence; early infant HIV-1 diagnosis; early treatment; paediatrics.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Anti-HIV Agents / administration & dosage
Anti-HIV Agents / therapeutic use*
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Child, Preschool
DNA, Viral / metabolism*
Drug Administration Schedule
HIV Infections / drug therapy*
HIV Infections / virology
HIV-1 / genetics*
Humans
Infant
Infant, Newborn
Time-to-Treatment*

Substances

Anti-HIV Agents
DNA, Viral

Abstract

Publication types

MeSH terms

Substances

Grants and funding