February 24, 2005
The EuroSIDA collaboration is an enormous cohort in 29 European countries that has been the source for numerous important insights regarding treatment over the past many years. At this conference, an analysis was presented to explore the risk of AIDS or death given the variety of different antivirals that have been in wide-scale use for the past 8 years.
Christian Holkmann-Olsen and colleagues sought to address the question of whether there is any reason for concern that some antivirals have a greater or lesser impact on keeping people free of illness while on treatment regimens.
We have ample data that demonstrates how many standard regimens can control HIV and result in improved CD4+ cell counts. However, historically, only indinavir (IDV, Crixivan) and ritonavir (RTV, Norvir) were actually tested in studies that were designed to show the benefits of not only HIV suppression, but of preventing illness and death. As indinavir and ritonavir became the standard for newer drugs to be compared to, studies generally had few patients who did not stay clinically well while taking highly active antiretroviral therapy. There remains, however, some small but lingering doubts regarding whether all antivirals are equally protective, given the absence of actual proof in the studies done. Holkmann-Olsen's results provide additional reassurance that our current regimens are not only effective at controlling HIV, but at maintaining health.
In this cohort study, 6,814 people were monitored, representing 22,766 patient-years of follow-up. To be included, people had to be on antivirals, with a median time of starting in 1997.
The results were clear -- regardless of a patient's baseline CD4+ cell count and HIV-RNA level, all regimens looked at in this study resulted in similar decreases in rates of illness and death. The study had sufficient numbers to state that this is the case not just for the protease inhibitors, indinavir and ritonavir, but for boosted and unboosted saquinavir (SQV, Fortovase, Invirase), nelfinavir (NFV, Viracept), and the non-nucleosides nevirapine (NVP, Viramune) and efavirenz (EFV, Sustiva, Stocrin). In addition, there were no clear differences observed between the nucleoside/nucleotide reverse transcriptase inhibitor pairs zidovudine (AZT, Retrovir) + lamivudine (3TC, Epivir), stavudine (d4T, Zerit) + lamivudine and stavudine + didanosine (ddI, Videx).
Overall, although these results are not surprising, they are nevertheless reassuring. The authors caution that such cohort studies are not the way to compare one drug combination to another -- factors such as tolerability are not captured in this analysis, for example.
However, the results do support the understanding that as we work to control HIV and monitor improvements in the immune system, we can anticipate that whatever drugs we select to suppress HIV and thereby maintain these protective CD4+ cell counts, we are also simultaneously doing what is needed to keep people well.