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Continuous HAART and the Law of Diminishing Returns

French Researchers Question Benefit of Lifelong Antiretroviral Treatment

tagline 2004 August

The following are excerpts from "Effect of highly active antiretroviral therapy over 5 years," Jean-Pierre Viard and colleagues (Service d'Immunologie Clinique, Centre Hospitalier Universitaire Necker-Enfants Malades, Paris).

It is more and more difficult to imagine anti-HIV treatments as life-long prescriptions, given the side effects described in the long term, such as lipodystrophy (found here in nearly 60% of patients), metabolic disturbances, a possibly increased cardiovascular risk, mitochondrial toxicity and altered quality of life. In other words, the inconvenience of a very long-term treatment may outweigh the benefit of maintaining the CD4 cell count at a high level, considering that treatment beyond 2 to 4 years will not result in a significant further reduction of the HIV-1 DNA load. For patients with high CD4 cell values (e.g., >400 cells/mL) after this time [>2-4 years] on HAART, would it be reasonable to consider stopping therapy when the level of HIV-1 DNA reaches its lowest plateau and then wait for the patients to meet again the criteria for treatment initiation?

The present study, although limited in its conclusions by the small number of patients, stresses the leveling off, with time, of the effects of HAART. Maintenance of therapy beyond 3 years is necessary to avoid the replenishment of the compartment of cells actively producing virus, but any additional benefit in terms of reduction of the viral reservoir seems highly unlikely.

[Among patients enrolled in this study] there was only a very slight gain in CD4 cells after 18 months of treatment. Interestingly, the absolute increase in the CD4 cell count was not different in the patients with CD4 baseline values below or above the median value of the population, and there was no marked further benefit in the long term in either group. The majority of patients had reached a CD4 cell count constantly >400 cells/mL by month 30, and nearly all of those with a baseline CD4 cell count above the median (135 cells/mL) had attained that level at the end of follow-up. For patients who have reached this level of CD4 cell counts, a reasonably safe level both for the protection against opportunistic infections and for considering treatment interruption, the immunological benefit of maintaining HAART appears debatable.

In summary, the data presented here show that HIV-1 DNA does not seem influenced by HAART after the third year and confirm that the CD4 cell count gain is less apparent after 18 months on treatment. Based on these observations, we question the benefits of a lifelong treatment for HIV infection.

Source: Jean-Pierre Viard and colleagues: "Effect of highly active antiretroviral therapy over 5 years." AIDS 2004;18:45-49.