Prompt Initiation of Antiretroviral Therapy Associated With Low Viral Reservoirs at Birth

Prophylaxis against mother-to-child HIV transmission resulted in low viral reservoirs at birth; however, viral rebound was common, according to the results of a study published in the Journal of Infectious Diseases.

The Ucwaningo Lwabantwan observational study was conducted in South Africa. Newborn infants (N=164) of mothers infected with HIV were assessed for HIV reservoir at £21 days of life, and viral suppression and rebound were assessed through the first 3.5 years. Routine antenatal combination antiretroviral therapy (cART) was defined as fixed-dose emtricitabine, tenofovir disoproxil fumarate, and efavirenz; infant cART was defined as zidovudine, lamivudine, and nevirapine until 28 days then abacavir, lamivudine, and ritonavir-boosted lopinavir.

Initiation of cART occurred at a median of 6.5 (range 1-21) days of life. Baseline median HIV DNA level was 2.8 (range, 0.7-4.8) log₁₀ copies/million peripheral blood mononuclear cells (PBMC). Male infants tended to have 0.5 HIV log₁₀ copies/million PBMC lower female infants.

At baseline, 98 infants were found to be virally suppressed. Compared with baseline values, no characteristics differed significantly on the basis of viral suppression status except plasma viral load (median, 3700 vs 9700 copies/mL; P =.04). Time to DNA half-life among the infants with viral suppression was 28 days; however, maintenance of aviremia was low (46%) at 6 months.

Baseline DNA levels were associated with plasma viral load (b, 0.22; 95% CI, 0.14-0.3; P <.0001), CD4% (b, -0.03; 95% CI, -0.04 to -0.02; P <.0001), and absence of antenatal cART (b, 0.61; 95% CI, 0.24-0.98; P =.002).

Significant contributors to HIV decay included duration of cART (effective degrees of freedom [EDF], 3.19; P <.0001), plasma viral load over time (EDF, 1.00; P <.0001), and infant age at suppressed status (EDF, 1.00; P =.0003). Decay over the first 3.5 years of life was nonlinear (R², 0.84; P <.0001).

Time to viral suppression was associated with baseline infant CD4% (adjusted hazard ratio [aHR], 1.02; 95% CI, 1.01-1.04; P =.008), infant HIV DNA (aHR, 0.75; 95% CI, 0.60-0.94; P =.01), and infant plasma viral load (aHR, 0.55; 95% CI, 0.45-0.66; P <.0001).

Among infants with high (>1000 copies/mL) and lower (>100 copies/mL) HIV RNA, infant age at viral suppression (HR, 0.93; 95% CI, 0.88-0.98; P =.009; HR, 0.95; 95% CI, 0.91-0.99; P =.02, respectively) was associated with time to viral rebound.

This study may have been limited by using 2 methods for collecting infant blood samples, point-of-care and dried blood spot tests, which may have biased some findings.

This study indicated a birth diagnosis of HIV and cART initiation during the first 3 weeks of life was associated with viral suppression among many infants; however, viral rebound was common. Mother-to-child prophylaxis against HIV transmission in utero was associated with reduced HIV DNA at birth.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Milar JR, Bengu N, Vieira VA, et al. Early initiation of antiretroviral therapy following in utero HIV infection is associated with low viral reservoirs but other factors determine subsequent plasma viral rebound. J Infect Dis. Published online May 8, 2021. doi:10.1093/infdis/jiab223.