Results of a study published in Clinical Infectious Diseases indicate treatment-naive patients with low CD4+ counts and high HIV viral loads experience significantly weaker responses to preferred first-line antiretroviral therapy (ART) regimens.

Researchers conducted a systematic review and meta-analysis to assess whether low CD4+ counts and high HIV viral loads affect outcomes of preferred first-line ART regimens. Data were sourced from 12 randomized controlled trials, published between 2009 and 2019.  Eligible studies included those conducted among treatment-naive adult patients with HIV infection receiving first-line ART that had a follow-up period of at least 48 weeks. Patients included in the analysis were assessed in subgroups based on CD4+ cell count (≤200 cells/µL vs >200 cells/µL) or HIV viral load (>100,000 copies/mL vs <100,000 copies/mL).

The final analysis comprised patient data from 17 subgroups based on CD4+ count (n=6597) and 21 based on HIV viral load (n=6846). Overall, the median patient age was 34 (IQR, 33-37) years, most patients were men, the median percentage of patients with an HIV viral load of more than 100,000 copies/mL was 26.4%, and the median percentage of patients with a CD4+ count of less than 200 cells/µL was 13.4%. 

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Study findings revealed an increased risk for treatment failure at 48 weeks among patients with low vs high CD4+ counts at ART initiation (≤200 cells/µL vs >200 cells/µL; odds ratio [OR], 1.94; 95% CI, 1.45-2.61). An increased risk for treatment failure at 48 weeks was also observed among patients with high vs low HIV viral loads at ART initiation (>100,000 copies/mL vs <100,000 copies/mL; OR, 1.75; 95% CI, 1.30-2.35).

Results were similar at 96 weeks, with an increased risk for treatment failure observed among patients with either high CD4+ counts (OR, 1.46; 95% CI, 1.01-2.11) or low HIV viral loads (OR, 1.54; 95% CI, 1.26-1.88) at ART initiation. 

These findings were not affected by the exclusion of patients in each subgroup who were receiving dolutegravir plus lamivudine-based ART regimens.

Of note, the highest incidence of treatment-emergent resistance to integrate strand transfer inhibitors and nucleos(t)ide reverse transcriptase inhibitors at the time of treatment failure was observed in subgroups comprising patients receiving raltegravir-based ART regimens. However, the researchers noted the need for further research to alleviate the moderate uncertainty surrounding this finding.

This study was limited as patients may not have been randomly assigned to subgroups, suggesting a potential lack of homogeneity within each subgroup. In addition, only studies assessing patients receiving recommended first-line ART regimens were included in the analysis. 

“Success of treatment in patients with low CD4 counts and/or high viral loads seems to be independent of the drugs included in the ART regimen, provided they are currently recommended first-choice options,” the researchers concluded.

Disclosures: Multiple study authors declared affiliations with pharmaceutical, biotech, and/or device companies. Please see the reference for a full list of disclosures.


Pérez Molina JA, Crespillo-Andújar C, Zamora J, et al. Contribution of low CD4 cell counts and high HIV viral load to the efficacy of preferred first-line antiretroviral regimens for treating HIV infection: a systematic review and meta-analysis. Clin Infect Dis. Published online March 28, 2023. doi:10.1093/cid/ciad177

This article originally appeared on Infectious Disease Advisor