The prognosis of people with HIV can be more accurately determined after six months of treatment rather than at baseline, and very small increases in CD4 cell count appear to confer big benefits in reducing the risk of disease progression or death, according to an analysis of 13 cohorts published this week in The Lancet.
Until now, it had been widely assumed that CD4 count and viral load at the beginning of treatment were the best guide to long-term survival and disease progression once treatment was started. This assumption was based on information from individual cohorts such as the British Columbia cohort in Canada, and an analysis of HIV-positive cohorts from Europe and Canada.
In the new study, Matthias Egger of the University of Berne led an analysis of HIV-positive cohorts from Europe and Canada (the Antiretroviral Cohort Collaboration) in which 9,223 patients initiated treatment with at least three drugs. The group analysed the clinical outcomes of all patients with viral load and CD4 measurements available prior to commencing therapy and after six months on treatment. The median follow-up was one year, and the available data covered 13,408 person-years of follow-up.
During the follow-up period, the cohorts recorded 142 deaths and 263 patients experienced at least one AIDS-defining illness, of which the most frequent were non-Hodgkin lymphoma, oesaphageal candidiasis, tuberculosis and Kaposi’s sarcoma.
When the statisticians controlled for the CD4 cell response after six months of treatment, they found that the baseline CD4 cell count ceased to predict the risk of death or disease progression. Instead, prognosis depended on the absolute CD4 cell count after six months of treatment rather than changes since the start of treatment.
The researchers found that when compared with patients who had CD4 cell counts below 25 cells/mm3 after six months on treatment, those with CD4 counts between 25 and 49 cells/mm3 had a 45% lower risk of death during the follow-up period, whilst those with CD4 cell counts above 100 cells/mm3 had a >80% lower risk of death (rising to 93% lowered risk in the group of patients who started treatment with a CD4 cell count above 350 cells/mm3).
At lower CD4 cell counts the differences in viral control after six months on treatment had a much greater projected impact on the risk of disease progression or death when compared with patients with CD4 cell counts above 100 cells/mm3. When the researchers modelled the risk of disease progression or death according to the six month response, using data from patients treated for up to 3.5 years (n=509), they found that individuals with viral load below 500 copies at six months were approximately 25% less likely to have experienced disease progression or death when compared to those with viral load above 100,000 copies/ml after six months.
Age greater than fifty years, infection through intravenous drug use and an AIDS diagnosis at baseline or within six months of starting HAART were also associated with an increased risk of disease progression.
The authors say that the most important message of their study is that “it matters what CD4 cell count and viral load a patient arrives at, but not where the patient was when starting HAART. This should be seen as a positive message, which might help to motivate patients to adhere to treatment regimens.”
However, they also add that their findings show that every CD4 cell gained on treatment is important in patients with low baseline CD4 cell counts, suggesting that people with HIV should not be discouraged if the early response to treatment is slow.
The analysis will continue with further follow-up, and one question the researchers are interested to answer is: will relatively small differences in response lead to divergent responses as time goes on and the cohorts accumulate data on greater numbers of patients? Will relatively small CD4 responses after 12 months of treatment still confer as much apparent benefit as responses after six months?
Reference
The Antiretroviral Therapy (ART) Cohort Collaboration. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. The Lancet 362:679-86, 2003.