September 23, 2012
Ongoing HIV infection of CD4+ cells may be the reason why some individuals with undetectable viral loads exhibit poor CD4+ cell count responses, according to study results presented at ICAAC 2012.
Researchers in Montpellier, France, used a qPCR assay to look for HIV DNA in the CD4+ cell cytoplasm. They posited that since cytoplasm has a short half-life, it could be a reliable marker of recent CD4+ cell infection.
The investigators studied CD4+ cell samples from virologically suppressed individuals who were on treatment. Further baseline information was reported by NATAP:
Twenty-five of 35 study participants were men, and their age averaged 48 (range 30 to 70). Duration of HIV infection averaged 7 years (range 1 to 18), and CD4 count averaged 491 (95% confidence interval [CI] 408 to 552). Sixteen people were taking a protease inhibitor, 11 each were taking a nonnucleoside or an integrase inhibitor, and 7 were taking a CCR5 antagonist.
The researchers found the presence of HIV DNA in the CD4+ cell cytoplasm of 10 of the participants, according to the study abstract. Average CD4+ cell count trends were lower in these 10 individuals (-4 CD4+ cells per month) than in the other 23 individuals (+13 CD4+ cells per month). Though the study group was small, this finding was statistically significant (P = .035).
The researchers also compared immune responses by measuring CD38, a marker for immune activation, at the surface of CD8+ cells in a subgroup of 20 participants. The percentage of activated CD8+ cells in the individuals with detectable cytoplasmic HIV DNA rose an average of 1.7% monthly, whereas in the other individuals it decreased an average of 0.5% monthly (P = .052). This finding further suggested that ongoing HIV infection was occurring despite virologic suppression.
The investigators believe their findings "argue for a role of ongoing HIV infection in the persistence of immune activation and in the impairment of immune restoration in some virologic responders." They suggested that their assay may offer a simple way to assess the potency of antiretroviral regimens, to monitor ART simplification, to determine which patients may need a stronger regimen, and to distinguish ongoing CD4-cell infection from other causes of poor CD4 gains.
While these findings could lead to better ways of increasing CD4+ cell counts in people living with HIV, more research needs to be done in larger groups.
Warren Tong is the research editor for TheBody.com and TheBodyPRO.com.
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