HIV-positive individuals can safely delay initiating HAART until their CD4 cell count falls to 200 cells/mm3 - provided they are adherent to their therapy, according to a Canadian study published in the November 18th edition of the Annals of Internal Medicine. The Canadian investigators also found that provided a patient is adherent to their therapy, individuals who started anti-HIV treatments when their CD4 cell count was 200 cells/mm3 were just as likely to survive as those who initiated HAART with a CD4 cell count of 350 cells/mm3 or above.
The optimum time to start anti-HIV therapy is not known. The current treatment guidelines of the British HIV Association state that an individual should start HAART before their CD4 cell count falls to 200 cells/mm3 and that HAART should be considered if a patient's CD4 cell count is between 200 cells/mm3 and 350 cells/mm3. Other treatment guidelines, most notably those in the US have been more cautious, recommending the use of HAART at higher CD4 levels, based partly on studies suggesting poorer survival in patients who delayed HAART until their CD4 cell count had fallen below 350 cells/mm3.
Canadian investigators from the HAART Observational Medical Evaluation and Research (HOMER) study noted that these studies had not looked for patient adherence, a key predictor of the success of HAART. Therefore they wished to establish the interaction between baseline CD4 cell count and levels of adherence on survival rates after the initiation of HAART.
The study involved 1,422 patients who started HAART between 1996 and 2000 and who received follow-up until Spring 2002. Patients were stratified according to their baseline CD4 cell counts, and individuals were further stratified into adherent and non-adherent categories according to prescription refill records for the first year of HAART. Patients were categorised as non-adherent if they received less than 75% of HAART in their first year of therapy.
In addition, the investigators conducted a subanalysis which looked at the risk of death amongst patients who were highly adherent to therapy, taking at least 95% of their HAART. Deaths were censored to exclude accidents and suicide, and mortality rates were calculated for each baseline CD4 category.
The median duration of study follow-up was 40 months, and at baseline patients had a median age of 37 years, median CD4 cell count of 270 cells/mm3 and median viral load of 120,000 copies/mL.
During the study period 193 patients died, 25 as a result of accident or suicide and 14 due to drug overdose.
The mortality rate amongst patients who were at least 75% adherent and started HAART before their CD4 cell count fell to 200 cells3 was 7%. Conversely, the mortality rate for individuals who started HAART with a similar baseline viral load but who were less than 75% adherent was significantly higher (15.2%). Further, the investigators found that there was no extra survival benefit gained from starting HAART at CD4 cell counts above 200 cells/mm3 provided that patients were 75% adherent to therapy (p>0.2).
In the subanalysis which excluded deaths due to non-HIV causes and only looked at patients with adherence of 95% or greater, investigators once again found that there was no extra survival benefit to be gained from starting HAART at a CD4 cell count above 200 cells/mm3 (p>0.2).
The importance of adherence to survival was further demonstrated by the investigators, who established that even amongst individuals who started HAART with a CD4 cell count of 250 cells/mm3 or greater, non-adherent patients had a statistically elevated risk of mortality compared to individuals who took at least 75% of their therapy. Indeed, the mortality rate seen in non-adherent patients with a CD4 cell count of 350 cells/mm3 or above was similar to that seen in non-adherent patients with a baseline CD4 cell count of 200 cells/mm3 (adjusted relative hazard 2.56, 95% CI, 1.36 – 4.84, p
The investigators conclude, “these data suggest that patient nonadherence, instead of when antiretroviral therapy is initiated before a CD4 [cell count of 200cells/mm3], may be the strongest determinant of patient survival. These results should be useful for patients weighing the difficult decision about the optimum time to initiate HAART and for the ongoing development of therapeutic guidelines.”
Further information on this website
What level of adherence is needed?
Adherence- factsheet
Adherence - booklet in the information for HIV-positive people series (pdf)
Wood E et al. Effect of medication adherence on survival of HIBV-infected adults who start HAART when CD4 cell count is 0.200 to 0.350 X 109 L. Annals of Internal Medicine 139: 810 – 816, 2003.