An analysis of about 1,500 people showed that those starting therapy with either hard gel saquinavir (Invirase) or nelfinavir were less likely to achieve viral loads below 500 copies within 24 weeks of therapy. They were also more likely to have their viral loads rebound above 500 copies compared to people who started with indinavir, ritonavir or two protease inhibitors.
Eighty-five percent of the participants used three drugs; the rest used four or more. People who started with high viral loads and low CD4+ cell counts and those who started with one or two new drugs were least likely to have sustained responses.
Although this was expected in the case of hard gel saquinavir, known to have serious absorption problems, it was a surprise for nelfinavir. No obvious reason was given as to why nelfinavir fared so poorly. While there are limitations to observational studies, two other recent studies raised similar questions about nelfinavir, including ACTG 364 and the European COMBINE study.
|Regimen||% with Viral Load <500 Copies HIV RNA|
|NFV + 2 NARTIs||35%|
|EFV + 2 NARTIs||60%|
|NFV + EFV + 2 NARTIs||74%|
|NFV = nelfinavir|
EFV = efavirenz
NARTIs = nucleoside analogue reverse transcriptase inhibitors
Those taking combinations including efavirenz or efavirenz + nelfinavir were more likely to maintain good HIV control than those taking only nelfinavir. There was no difference in the suppression of HIV between these two groups. No difference in the rate of side effects was seen among the three groups.
Another surprising finding was that all study groups looked equivalent at the end of 16 weeks, originally planned as the end of the study. However, longer-term follow-up showed a real difference developed between the regimens. This should remind us that short-term studies can be misleading.
|NFV + ATZ/3TC||33%||22%|
|NVP + ATZ/3TC||58%||57%|
|NFV = nelfinavir NVP = nevirapine|
A = All patients, % with viral load <20 copies HIV RNA.
B = Subgroup, % of patients starting with viral load above 100,000 copies who reached viral load <20 copies HIV RNA. Anti-HIV Drug Update
What complicates this further is that the current federal Guidelines lists nelfinavir-based combinations as "preferred" and the nevirapine-based ones as "less desirable" -- the opposite of these new findings. Since the approval of nelfinavir, Project Inform has publicly questioned whether it offers the same potency as indinavir and ritonavir. Now that studies have raised the same question, the burden is on federal authorities to decide what to do. One study suggesting inferiority may not be enough to question the value of a drug, but aren't three studies enough?
For people already using nelfinavir and having a good response, these findings may not warrant changing regimens. But it suggests more frequent checking of viral load. For those making their first treatment decisions, the new data should become one more fact in deciding which therapy to begin. There are now so many options for first-time treatment that learning about the reduced potency for one of them doesn't necessarily create a crisis.
Back to the Project Inform Perspective April 2000 contents page.