Factors associated with proviral DNA HIV-1 tropism in antiretroviral therapy-treated patients with fully suppressed plasma HIV viral load: implications for the clinical use of CCR5 antagonists.

Objectives: Most treated HIV-1 patients have undetectable viral loads and the strategies for managing long-term side effects may involve a new class of antiretroviral-like CCR5 antagonists. Tropism determination based on proviral DNA sequence is necessary for patients with a fully suppressed plasma viral load, as assays analysing DNA phenotypes have yet to be developed. We aimed to analyse HIV-1 tropism using proviral DNA sequencing and the associated factors, in a group of patients on antiretroviral (ARV) treatment with an undetectable viral load in plasma.
Methods: Blood samples of 140 HIV-1-infected ARV-treated patients with a plasma viral load of <40 copies/mL were studied. All patients had never been treated with CCR5 antagonists. Co-receptor usage was determined using proviral DNA from the V3 env region sequence by Geno2Pheno (false positive rate 10%) and PSSM algorithms.
Results: Among 140 patients treated using ARV therapy with a fully suppressed plasma viral load, at least 70% of patients had proviral R5-tropic virus. Among all the studied factors (time since HIV infection diagnosis, treatment duration, time since viral load undetectability, HIV subtype, current treatment, age, number of treatment types, sex, genotypic susceptibility score, and nadir and current CD4 cell counts), nadir CD4 T cell count alone was associated with tropism during a multivariate analysis. R5X4/X4 tropism was present in all nadir CD4 categories.
Conclusions: Proviral DNA tropism determination should be required, even for patients with a CD4 nadir cell count >350 cells/mm(3), before CCR5 antagonists are used in patients with a fully suppressed plasma viral load.