Present drugs not expected to kill virus
Scientist envisions future of simpler regimens
The pendulum will swing back toward later treatment of HIV-infected patients, and the definition of failure of clinical trials will be revisited, predicted Mauro Schechter, MD, PhD, professor of infectious diseases at the Hospital Universitario Clementino Fraga Filho at Federal University of Rio de Janeiro in Rio de Janeiro, Brazil.
Schechter, who addressed the XIII International AIDS Conference in Durban, South Africa, and made predictions about what would happen by the time the international conference reconvenes in 2002 in Barcelona, foresees a greater emphasis on "delta viral load," the renaissance of CD4 count as a guide to therapy, and the availability of simpler drug regimens.
He also spoke about a renewal of interest in the prevention of opportunistic infections, which in turn will take into consideration local epidemiological conditions.
Schechter’s address re-emphasizes the point made by Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, MD, that the eradication of the virus with currently available drugs is unlikely.
Since the Geneva conference two years ago, data have accumulated showing that virologic failures are more common in practice than in trials and that opportunistic infections occur at similar CD4 cell counts in patients who are on therapy and those who are not, Schechter said. Although many patients did not achieve full immune recovery, a large proportion did achieve a "safe" level of immune competence, he added.
On a more cautionary note, he said antiretroviral therapy was associated with potentially serious side effects, some of which might be time-dependent.
Those newly acquired data have led to renewed debate on the optimum time to treat, the choice of initial drug regimens, when to change and how to sequence them, and how to simplify existing regimens, Schechter said. Emphasis has shifted to the role of new drugs, pharmacological enhancement in extending treatment benefits, and management and prevention of opportunistic infections.
Slope of viral load similar in some patients
In the course of his presentation, Schechter reviewed recent data on a wide range of issues related to HIV/AIDS treatment, making reference to the contested debate about the optimal time to initiate therapy, particularly in connection with threshold values of viral load and CD4 cells.
With regard to viral load, two recently published reports demonstrated a direct association between the slope of the increase of plasma viral load in the first few years after seroconversion and the probability of progressing to AIDS. "It was also shown that for those who progressed to AIDS, the slope of viral load increase in the three years preceding progression to AIDS was similar, regardless of prior AIDS-free time," Schechter said.
These observations argue against a blanket concept of a fixed set point, said Schechter. They also suggest that it may be more appropriate to measure viral load in a serial fashion, rather than relying on one or two measurements to make therapeutic decisions.
Schechter referred to a report to be presented at the conference by Julio Montaner, MD, national co-director of the Canadian HIV Trials Network, Ottawa, Ontario, on a population-based cohort analysis of antiretroviral naive patients in British Columbia who started HAART between August 1996 and September 1999.
Postponing therapy OK if immune levels safe
Results from the study, which involved 1,200 eligible participants, showed that effectiveness of therapy is dependent on baseline CD4 count, not on age, gender, viral load, prior AIDS diagnosis, or protease inhibitor (PI) use. "Furthermore, few patients with baseline CD4>200 cells/mm3 experienced clinical progression, and progression rates were similar for patients with CD4 counts of 200-350 or 350-500 cells/mm3.
The study also showed that it is probably correct to postpone treatment initiation as long as therapy is started while immune recovery to "safe" levels is still possible. However, the question of how to define this moment precisely remains unanswered.
Less-potent regimens likely in future
Schechter’s address tracked the progress made in the past two years but emphasized that many earlier conclusions had yet to be revisited. In summing up, he predicted that the future would see a re-evaluation of "less potent" regimens, particularly of their cost-effectiveness in resource-limited settings, which was a major focus of the conference.
Structured treatment interruptions would be discussed as a means of making treatment less toxic and more affordable, and pressure on industry and governments would increase to ensure equal and universal access to antiretroviral therapy, which is still unavailable to the majority of those infected with HIV in the developing world, Schechter said.
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