Low HIV DNA levels and strong HIV-specific immune responses associated with undetectable viral load without treatment

Patients who are able to maintain an undetectable viral load without antiretroviral therapy have very low and stable levels of HIV DNA and a strong HIV-specific immune response, according to a French study published in the October 1^st edition of Clinical Infectious Diseases. Although the number of patients who maintain viral control without anti-HIV treatment is below 1%, the investigators believe that these individuals may provide “new insights for vaccine development.”

It is well established that a small number of HIV-positive patients, often called long term non-progressors, maintain high CD4 cell counts without HIV therapy. The reasons for lack of disease progression in these patients is unclear, and it has been speculated that factors related to both the virus and the host may be the reason.

The definition of long term non-progressor does not take into account plasma viral load. French investigators noted that they had encountered a number of patients in clinical practice who maintained an undetectable viral load without HIV treatment. They therefore wished to describe the frequency of this phenomenon and the characteristics of patients who had spontaneous control of HIV.

Data from two French HIV cohorts with over 2800 patients were examined by the investigators. In order to be defined as a spontaneous controller of HIV, patients were required to be infected with HIV for ten years or more and to have maintained a viral load of below 400 copies/ml for at least 90% of the time without HIV therapy.

HIV DNA in peripheral blood mononuclear cells was quantified and HIV-specific CD8 and CD4 cell responses were measured. Analysis of CCR5 was also conducted.

“Patients with HIV controller status were rare,” observed the investigators, “comprising less than 1% of HIV-infected patients who were followed”. In total 15 individuals were identified. None had symptoms of HIV disease. Two patients were coinfected with chronic hepatitis B virus and seven individuals had chronic hepatitis C virus infection.

Median CD4 cell count was 750 cells/mm³ and was generally stable over time. However, an annual decline of a mean of 21 cells/mm³ was seen in ten patients.

Five patients never had a viral load above 50 copies/ml, the remaining ten patients experiencing “blips” in their viral load; eight had occasional blips above 50 copies/ml and two had up to 10% of viral load measurements above 400 copies/ml.

All 15 patients had very low levels of HIV DNA in their peripheral blood mononuclear cells (mean 32 copies/ml). A strong HIV-specific CD4 response was observed in seven patients, and a high HIV-specific CD8 cell count was seen in all 15 individuals (mean count 4,800 cells/mm³). CCR5 mutations did not appear to have a role in the spontaneous viral control these individuals achieved.

The investigators noted that patients taking potent HIV therapy who have good viral control have much lower HIV-specific CD8 cell responses than spontaneous controllers.

Three possible explanations for spontaneous control of HIV are advanced by the investigators:

• Like long term non-progressors, an attenuated strain of HIV may be involved.
• Particular cellular phenotypes may result in reduced susceptibility to HIV infection for CD4 cells.
• Patients with spontaneous control may have particularly efficient immune responses.

“Despite the rarity of HIV controllers, analysis of such persons offers a unique opportunity to improve our understanding of the pathogenesis of HIV infection”, conclude the investigators. They add that this research could assist in the development of an HIV vaccine.