The number of CD4+ T cells infected with HIV is predictive of CD4+:CD8+ ratio

Highly active antiretroviral therapy (HAART) can very dramatically decrease plasma viremia and improve CD4+ T cell counts. Despite these improvements, which may significantly improve patient morbidity and mortality, most individuals on HAART, even those with an undetectable plasma viral load, continue to have low-grade, ongoing HIV replication.

It has been speculated that this continued HIV replication may be responsible for chronically elevated levels of CD8+ T cells or abnormal CD4+:CD8+ T cell ratios observed in some patients on HAART, and data from a recent study from the National Institutes of Health (NIH) support this conclusion.

In the study, published in The Journal of Infectious Diseases, the investigators at the NIH evaluated the relationship between CD4+:CD8+ T cell count ratios and the frequency of CD4+ T cells carrying HIV-1 proviral DNA and of HIV-specific cytotoxic CD8+ T lymphocytes (CTLs).

The study enrolled 32 HIV-infected individuals who had been receiving HAART for >2.5 years and in whom plasma viral load was <50 copies/mL. In these patients, the mean CD4+ and CD8+ T cell counts were 840 cells/mm3 and 1110 cells/mm3, respectively, and the CD4+:CD8+ T cell ratio was 0.90.

Results

The investigators found a statistically significant inverse correlation between the frequency of CD4+ T cells carrying HIV-1 proviral DNA and the CD4+:CD8+ T cell ratio in these individuals. No correlation was found between the frequency of HIV-1-specific cytotoxic CD8+ T lymphocytes and the CD4+:CD8+ T cell ratios in those individuals.

The authors conclude, “These data suggest that persistent, low-level, ongoing viral replication, although not sufficient to maintain HIV-1-specific CTL responses, may explain, in part, why normalization of the CD4+:CD8+ T cell ratio is not achieved in some infected individuals successfully treated with HAART.”

Chun TW, Justement JS, Pandya P et al. Relationship between the Size of the Human Immunodeficiency Virus Type 1 (HIV-1) Reservoir in Peripheral Blood CD4+ T Cells and CD4+:CD8+ T Cell Ratios in Aviremic HIV-1-Infected Individuals Receiving Long-Term Highly Active Antiretroviral Therapy. J Infect Dis 2002 Jun 1;185(11):1672-1676
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd= Retrieve&db=PubMed&list_uids=12023777