Some HIV/AIDS Patients May Safely Delay Treatment Initiation, Two JAMA Studies ShowHighly active antiretroviral therapy has "changed the landscape of HIV care in the developed world," but because of its "significant adverse effects" doctors have "dealt with a pendulum effect in decisions regarding when to initiate therapy during HIV infection," with current guidelines suggesting that physicians hold off on beginning therapy until CD4 cell counts fall and viral loads rise, Dr. Roger Pomerantz of Thomas Jefferson University states in an op-ed in today's edition of the Journal of the American Medical Association (Pomerantz, JAMA, 11/28). Two studies examining the correlations between CD4 cell counts and viral loads and viral suppression and disease progression and appearing in today's JAMA suggest that some HIV patients can safely delay treatment initiation "longer than previously thought." The studies show that even if patients' CD4 cell counts are low (at least 200/mm3) and viral loads are high, the drugs are still beneficial and delaying treatment until this time "does no harm." Dr. Jeffrey Laurence, senior scientist at the American Foundation for AIDS Research, said, "It could be comforting to people to realize that watchful waiting won't harm you" (AP/Omaha World-Herald, 11/28). Pomerantz writes that although the studies offer "somewhat divergent clinical conclusions" on when best to initiate therapy, physicians can use the studies to "yield more clarity when determining when to initiate" treatment in HIV-positive patients (Pomerantz, JAMA, 11/28).
Andrew Phillips of the Royal Free and University College Medical School in London and colleagues analyzed three cohort studies conducted in Europe between 1996 and 2000 to determine the correlation between viral load response to HAART and baseline CD4 cell count and baseline viral load. The researchers found that lower CD4 cell counts and higher viral loads at baseline were not associated with poorer virological outcomes in patients on HAART. Eighty-five percent of the 3,226 treatment-naive patients experienced viral load suppression, defined as less than 500 copies/mL at 32 weeks, after HAART initiation. However, those with a baseline viral load greater than 100,000 copies/mL had a slower rate of viral suppression (Phillips et al., JAMA, 11/28). In the second study, Robert Hogg of the British Columbia Center for Excellence in HIV/AIDS and colleagues conducted a population-based analysis of 1,219 treatment-naive HIV-positive people over the age of 18 between August 1996 and September 1999 to determine the rates of disease progression stratified by baseline CD4 cell count and viral load prior to HAART initiation. The crude mortality rate for participants was 6.7% with no difference in mortality associated with either sex or age. CD4 cell count was the only statistically significant factor after a multivariate analysis. Patients with CD4 cell counts of less than 50/mm3 were 6.67 times more likely to die than those with CD4 counts of 200/mm3 or more, and those with counts of 50/mm3 to 199/mm3 were 3.41 times more likely to die than those with CD4 counts of 200/mm3 or more (Hogg et al., JAMA, 11/28).
Comparing the Results
The Phillips study suggests that antiretroviral therapy "should be withheld for indefinite periods before initiation in patients, at least when solely based on a potential response in plasma viral load," Pomerantz writes, adding that the Hogg study "confirms the prognostic value of baseline CD4 T-lymphocyte counts." Based on the two studies' findings, "it would seem prudent" to postpone treatment initiation for some patients until the CD4 cell count "approaches ... at least" 200/mm3, he says. However, for patients who have seroconverted in the previous six months, treatment should begin immediately, as they "may preserve HIV-specific T-helper cell function," he states. Pomerantz notes that neither study determined the subjects' times of seroconversion, or "lead-time biases," to consider in the analyses. "Further studies will be necessary to determine whether certain subgroups of patients, based on age or dynamics of CD4 T-lymphocyte decline, should be followed closely and therapy initiated at different stages of clinically documented immune suppression," he concludes (Pomerantz, JAMA, 11/28).