Evaluating structured treatment interruptions: rationale, experience, potential risks and benefits
Veronica Miller, PHD, Director, Interdisciplinary HIV Research, J. W. Goethe-Universitat, Frankfurt, Germany
Summary by Tim Horn, Edited by Calvin Cohen, MD, MS, and Martin Markowitz, MD
Considering the growing number of drawbacks and uncertainties associated with chronic antiretroviral therapy, it should come as no surprise that both clinicians and patients have found a great deal of optimism in structured treatment interruptions (STIs). A number of researchers, including Dr. Veronica Miller, have hypothesized various rationales for discontinuing treatment in some HIV-infected patients, even for short periods of time:
- Patients grappling with adherence issues. Poor adherence has been identified as a leading cause of drug failure among patients receiving combination therapy. Stopping therapy in these patients, at least until barriers to adherence can be dealt with, might prove to be a short-term preventive solution to a long-term dilemma – multiple drug resistance.
- Side effects. There may be a benefit in initiating an STI to help control or reverse some of the long-term toxicities associated with HAART. It is still not known, however, if temporary cessation of therapy has any significant impact on side effects such as elevated liver function, peripheral neuropathy, or nutritional disorders (e.g., body-habitus changes or metabolic complications). A study, being conducted by the National Institutes of Health, is currently studying pulsed antiretroviral therapy as an approach to decreasing toxicities.
- Pregnant women. According to both the United States Public Health Service and the International AIDS Society-USA, antiretroviral therapy is of considerable benefit in reducing perinatal HIV transmission rates. However, few data are available to indicate that antiretrovirals are safe for a developing foetus during the first trimester of pregnancy when teratogenicity is most common. In turn, STIs may be a feasible option for HIV-infected women receiving HAART prior to pregnancy, carried through to the second trimester when such side effects are less common.
- Patients with multiple-drug resistance and experiencing treatment failure. Given the lack of effective options for patients with multiple-drug resistant HIV variants and few remaining treatment options, STIs have been suggested to be a worthwhile effort. As discussed by Dr. Miller, STIs in the setting of treatment failure appear to halt the evolution of additional mutations conferring drug resistance and, in many cases, allow for a shift to drug-sensitive wild-type virus.
- Boosting HIV-specific cellular responses. Preliminary data suggest that STIs may induce immune responses capable of controlling, albeit partially, HIV replication. This rationale was also discussed by Dr. Miller and may prove to be the most important benefit associated with STIs.
Source: The PRN Notebook, June 2000, Vol. V, Num. 2.