Geneva, Switzerland -- Fifty-five percent of HIV patients who had achieved undetectable levels of the virus with combination antiretroviral therapy are projected to experience a resurgence of the virus within one year, according to San Francisco AIDS specialists.
Results of a community-based study were reported here today (June 30) at the 12th World AIDS Conference. The study was a combined project of the University of California San Francisco and the Community Consortium, an association of 200 health care providers who care for the majority of HIV/AIDS patients in the San Francisco Bay Area.
Though a majority of the 233 patients in the study experienced a "breakthrough," or a return of the virus to a detectable level, the patients remained generally healthy, with only three suffering from a significant HIV-related opportunistic infection or malignancy during an average of 10 months of follow-up, said lead author John Nienow, MD, UCSF assistant clinical professor of medicine.
"It's good news that the vast majority of patients are doing well clinically, though over one-half had a resurgence in their viral load. What is surprising is that, so far, many of the viral load breakthroughs have not been very high, and we have seen very little progression of HIV disease," Nienow said.
"These findings suggest that maintaining undetectable viral load levels may not be necessary to sustain wellness. Loss of viral suppression doesn't appear to lead automatically to clinical progression of disease," he added.
Donald Abrams, MD, chair of the Community Consortium and UCSF professor of medicine at the UCSF-affiliated San Francisco General Hospital, presented the research results at the World Conference.
The patients, treated at 10 sites in the Bay Area, were mostly men, and 36 percent were minorities. Five individuals had a history of injection drug use. Fifty-five percent of the patients had a diagnosis of AIDS, and 51 percent had fewer than 200 T-cells at the start of the study. Thirty-nine percent of the patients had never received any antiretroviral treatment before beginning combination therapy.
All of the patients had viral loads that became undetectable (below 500 copies per milliliter, using branched-chain DNA technology) as a result of having initiated antiretroviral combination therapy or having switched to a new regimen within the previous three months. About three-quarters of the patients had been placed on a three-drug regimen that included a protease inhibitor.
The researchers did not intervene in the patients' therapy or check on their compliance with the prescribed treatment but simply followed their progress, recording their viral load test results and T-cell counts every four months. They also monitored the patients to see if they developed any AIDS-defining illness during the study period.
After an average follow-up of 10 months, the median viral load at return to detectability in the study population was 2932 copies per milliliter, still considered relatively low, Nienow said.
"One of the interesting findings is that if people break through, they may do so at a low level, which may have significance in terms of clinical progression. It has been my experience that patients on therapy who break through at low levels remain at low levels and stay well," he noted.
The researchers looked at various factors--including T-cell counts, treatment histories, and the number of prescribed drugs in a regimen--that might predict which patients would experience a breakthrough. The only factor that appeared to be relevant was the patients' viral load before they achieved an undetectable level, he said. Those patients who had higher viral loads before starting combination therapy that resulted in an undetectable viral load were more likely to experience a return to detectability than those with lower viral loads, Nienow said.
A number of factors have been associated with a return to detectable viral load, including the development of drug-resistant strains of HIV, non-adherence to therapy, and length of infection--none of which could be assessed in this study.
"We don't yet have a clear picture of how relatively low levels of detectable viral load impact progression of disease," he said. "Breakthrough viral load is often recommended as a reason to change treatment, when more clinical predictors may now need to be taken into account," he added.
"We may need to raise the viral load level at which we make decisions to change treatment. If we use very low levels of detectable viral load as an indicator of treatment failure, we may be switching people from clinically successful regimens prematurely, thus depriving them of treatment options they may need in the future," he added.
In addition to Abrams, Nienow's colleagues in the study are Tarek Elbeik, PhD, UCSF assistant researcher/medicine; Peter Bacchetti, PhD, UCSF associate professor of biostatistics/epidemiology; Thomas Mitchell, MPH, research specialist; Carroll Child, RN, MSc, administrative nurse II; Starley Shade, MPH, statistician; and Jane Pannell, RN, clinical nurse II.
The Community Consortium was formed in 1985. Its membership includes health care providers in private practice and those who work at publicly-funded clinics, academic medical centers, and health maintenance organizations.