Early initiation of antiretroviral therapy (ART) prevents disease progression and shortens time to viral suppression in infants with HIV, according to a study published in the Journal of Acquired Immune Deficiency Syndromes.
Researchers analyzed virologic, immunologic, sociodemographic, and treatment-related data for infants born between 1997 and 2013 who were perinatally infected with HIV-1 (N=312). The standard ART regimen included either boosted protease inhibitors (bPIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) plus 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) for those infants who started treatment within 6 months of age (n=469). Baseline measurements included age, viral load, and CD4+ T-cells as a percentage of total lymphocytes (CD4%). Researchers used parameter fitting methods to estimate baseline viral load, decay rates, and time to viral suppression for infants with strictly declining viral load (n=188).
A majority of the infants showed viral suppression after starting standard ART at a median age of 82 days (n=276), and were virally suppressed for a median 132 days. Infants with shorter time to viral suppression initiated treatment at younger ages, had a lower baseline viral load and higher baseline CD4%. Infants with erratic decay patterns had more changes in treatment and accumulated treatment interruptions, suggesting treatment-related challenges such as poor adherence, drug resistance, toxicity, or irregular drug administration. Infants with immediate suppression started treatment significantly earlier (P =.015) and had significantly lower baseline viral load (P <.001). Low baseline viral load and high baseline CD4% were major factors contributing to shorter time to viral suppression, as predicted by mathematic modeling.
Limitations of this study included uncertainty about time of infection (in-utero or intrapartum); in-utero infections may confound age effect on time to viral suppression. The sparseness of virologic measurements did not allow for proper identification of all parameters in the simple phenomenologic-based mathematic model used to describe the decay in the viral load during treatment. Available virologic and immunologic measurements were sparse; baseline measurements and regular measurements during the initial viral load decay were often missing. Researchers attempted to remedy this by using a nonlinear mixed-effect model approach to compensate for missing data with a population mean.
“Data presented here support the fact that age at the start of ART is less helpful than markers of infections such as [viral load] and CD4% to determine [time to viral suppression],” the researchers concluded. “In addition to a low viral load and a high CD4% at start of treatment, [an immediate or monotonic] viral load decay pattern might predict an initially successful treatment response resulting in rapid times to viral suppression. Early-ART initiation combined with a fast viral suppression may lead to a reduction of the early established latent viral reservoir by shortening the viral exposure time. As a next step, the effect of these criteria on sustained VL suppression has to be investigated.”
Schröter J, Anelone AJN, Yates AJ, de Boer RJ. Time to viral suppression in perinatally HIV-infected infants depends on the viral load and CD4 T-cell percentage at the start of treatment [published online January 7, 2020]. J Acquir Immune Defic Syndr. doi: 10.1097/QAI.0000000000002291