September 24, 2002
The 24-week data for this trial was first presented during the last Retrovirus conference as a poster by Dr. Grace McComsey (poster 701T). Due to the ever-growing number of medical meetings that seem to plague the HIV/AIDS field, it's easy to find multiple presentations of the same study with periodical updates of the study results. This decreases the power of these studies (because of the multiple reviews of the data), and gives the presentation and the meeting a déjà vu feeling.
This phase IV, open-label, multicenter 48-week switch study was designed to assess the regression of lipoatrophy and hyperlactatemia in HIV-1 subjects in whom abacavir (ABC, Ziagen) or zidovudine (AZT, administered as Combivir) was substituted for the stavudine (d4T, Zerit) they were previously treated with. All subjects must have been taking a stavudine-containing regimen for at least six months, have undetectable HIV-1 RNA (less than 400 copies/mL) and have one of the following symptoms: physical findings of lipoatrophy (via physical exam or self report); symptoms compatible with hyperlactatemia and lactate levels greater than 2.2 mmol/L; or asymptomatic lactate levels greater than 3.2 mmol/L.
DEXA scans and single abdominal computerized axial tomography scans were used to measure the effects of switching medications. Hyperlactatemia changes were determined by changes in lactate levels. Subjects with confirmed entry lactates greater than 2.2 mmol/L were, at the discretion of the investigator, given the option to discontinue antiretroviral therapy (ART) until lactate levels were either less than 2.2 mmol/L or were asymptomatic. One hundred and eighteen patients were enrolled, 102 had normal lactate and 16 had high lactate levels. Most patients had low viral loads (mostly undetectable) and 80 percent had years of continuous stavudine exposure.
The bottom line is that patient fat improved about 20 to 30 percent as measured by DEXA in all compartments (arms, legs and trunk). Improvement in SAT and decreased VAT in both groups were also observed in the single CT scans of the abdomen. The improvements were greater in the group that switched to abacavir than in the group that switched to zidovudine.
The incidence of hypersensitivity reaction with abacavir was 4/80, or approximately 5 percent. Not surprisingly (all patients had very mild elevations), lactate levels decreased in the group of patients who had entered the study with high lactate levels. Viral load remained suppressed in most patients. Although the number of cases was small, none of the patients initially diagnosed with symptomatic hyperlactatemia experienced relapse.
In conclusion, this study supports other randomized trials like MITOX that have shown improvements of fat lipoatrophy after the substitution of zidovudine by abacavir. This is the longest follow-up study presented so far.
The main problems of this otherwise interesting study were pointed out by the presenter -- the sample size is relatively small (although not bad at all), some patients might have been misclassified as having hyperlactatemia (although this seems unlikely), and there was no control arm, which makes it difficult to know if the changes observed in the trial were due to the medication change or other reasons unaccounted for.
|Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.|