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Advocates Decry Drastic Cuts Proposed for California HIV/AIDS Funding

Currently recommended combination antiretroviral therapy (ART) regimens can reduce HIV viral load to "undetectable," or < 50 copies/mL using standard tests. Nonetheless, ultrasensitive tests reveal that very low levels of the virus (residual viremia) remain present over the lifetime of almost all HIV positive people despite use of potent HAART. There is controversy among experts, however, about whether this persistent low-level viremia results from ongoing cycles of viral replication or virus being released from latent viral "reservoirs."

To evaluate this issue, researchers at the Johns Hopkins University School of Medicine, the National Institutes of Health (NIH), and colleagues conducted 2 small, prospective treatment intensification trials to assess the effect of intensifying therapy by adding to the existing potent HAART regimen another anti-HIV drug not previously used by the patient. Results of the study appear in the May 21, 2009 online edition of the Proceedings of the National Academy of Science USA.

A total of 17 participants with viral load < 50 copies/mL were enrolled:

  • 10 patients at Johns Hopkins added ritonavir-boosted atazanavir (Reyataz) to their existing regimen, and
  • 7 participants at the NIH added either efavirenz (Sustiva) or lopinavir/ritonavir (Kaletra);
  • 2 patients (1 in the atazanavir group, 1 in the efavirenz group) dropped out before completing intensification and were excluded from further analysis.

Using an extremely sensitive HIV RNA assay with a limit of detection of 1 copy/mL, the 15 remaining patients all had > 1 copy/mL during at least 1 screening visit before intensification, and 9 had HIV RNA levels persistently > 1 copy/mL at a majority of pre-intensification time points.

The investigators discovered that intensification of HAART with any of the 3 different antiretroviral drugs did not further reduce levels of HIV viremia in these patients.

Furthermore, they found that lack of response to the addition of a potent new antiretroviral agent was not related to the emergence of drug-resistant virus or to suboptimal drug concentrations. Instead, the study authors wrote, "Our results suggest that residual viremia is not the product of ongoing, complete cycles of viral replication, but rather of virus output from stable reservoirs of infection."


Prior studies of HIV RNA viral kinetics have provided insights into the rate of viral replication, disease progression, and response to therapy. In the current study, the authors showed that intensification of HAART does not reduce residual viremia in patients with HIV RNA levels < 50 copies/mL but > 1 copy/mL.

The finding that there is no further decline in viremia with antiretroviral intensification "supports our thesis that standard combination therapy is maximally suppressive," stated the authors.

These results are consistent with those of 2 studies presented at this years Conference on Retroviruses and Opportunistic Infections (CROI 2009) in February, which showed that adding raltegravir (Isentress), a drug from the novel integrase inhibitor class, also did not further reduce viral replication in patients with HIV RNA < 50 copies/mL.

Because the findings of the present study support the hypothesis that residual viremia primarily represents output from stable reservoirs of infection, the investigators concluded, "Strategies for identifying and targeting these reservoirs may be the next important step in eliminating the persistence of HIV infection."
Johns Hopkins University School of Medicine, Baltimore, MD; Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, MD; Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD; Division of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD; Tufts University, Boston, MA; University of Pittsburgh School of Medicine, Pittsburgh, PA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore.



JB Dinoso, SY Kim, AM Wiegand, and others. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proceedings of the National Academy of Science USA. May 21, 2009. [Epub ahead of Print].

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