Therapeutic immune recovery and reduction of CXCR4-tropic HIV-1. Clinical Infectious Diseases
Bader et al. aimed at assessing the tropism of viral integrates in 35 HIV-positive patients’ blood during fully suppressive combination antiretroviral therapy (cART) by applying next-generation sequencing.
The relative frequencies of proviral X4-tropic HIV-1 variants decreased or stayed stable over time in the vast majority of patients (28 of 35 patients: 80%). In the remaining 7 patients (20%) with an increase of proviral X4-tropic HIV-1 variants, the documented expansion of X4-tropic provirus was based on the outgrowth of single viral variants from minority populations already present before therapy initiation. In 80% of the patients in this study decreasing proviral DNA loads were noted during successful treatment. However, in cases, in which overall proviral loads increased during therapy, there was no increase of the percentage of X4 tropic strains in the entire provirus population. Of note, all patients with an increasing percentage of X4 variants were homozygous for the wild-type CCR5 gene and did not carry a heterozygous or homozygous Δ32 genotype.
In conclusion, the study somewhat unexpectedly revealed that for patients with effectively suppressed viral loads X4-tropic HIV variants follow a persistent downward trend. The recently implemented World Health Organization strategies of immediate therapy initiation are fully in line with this gradual loss of X4 tropism during therapy. Moreover, the early use of coreceptor antagonists against the remaining CCR5-tropic viruses may be indicated.