The Body Covers: The 39th Annual Meeting of the Infectious Diseases Society of America
HIV/AIDS: Antiretroviral Therapy (Poster Session 87)
October 27, 2001
But are we just making the same error we did when we recommended "hit early, hit hard" without clinical data to support it? Maybe. We need prospective clinical trial data, but that is extremely complicated in the current setting, and a trial to evaluate this question will not be done -- at least not in the "developed" world. (I am sorry to say that I do not think it will be done in the developing world either.) If we want to be able to rationally approach this issue of when to start treatment, we need to look back at our experience and see what happened to patients who started treatment and then look at patients who did not start antiretroviral therapy at certain thresholds. It is not the best science, but this is life.
That is what Johns Hopkins University School of Medicine and others are starting to do.
They examined their database and selected patients who had a CD4 of more than 350 and looked at whether the patients started or did not start therapy. Therapy was defined as at least 90 days of a regimen including an HIV-1 protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or triple nucleosides with abacavir. The patients who began therapy were compared to those who did not. Endpoints included development of a new opportunistic infection (OI) or death, viral load at most recent visit, adverse drug reaction requiring change in regimen, and genetic resistance.
Patients were followed for a median of 29 months. They discovered that there was no difference in disease progression among persons who did or did not receive HAART. 284 patients initiated HAART during the study period, of whom 139 (49%) had received prior nucleoside reverse transcriptase inhibitor therapy. 402 patients did not initiate HAART. Median length of follow-up was 29 months. Among persons receiving HAART, 143 (50%) had undetectable viral loads. At the end of follow-up or most recent assessment, 135 patients (48%) were on their second HAART regimen and nine (3%) were on their third regimen. Lipodystrophy was reported in 30 (11%), and genotypic resistance in 62 (22%).
It is obvious that the patients who started therapy obtained a virologic benefit, but paid the price in toxicity without a clear impact on survival and AIDS-defining events (a short follow-up to see a benefit there).
The problem with the study is the selection bias. Patients who did not "need" therapy for four years are probably quite different from patients who did need therapy (with lots of long-term non-progressors in the first group). It would be fairer to follow patients who met the criteria for, let's say, the first year and see what happened to them over time. The sample size would be smaller, but it would give a better perspective of the long-term implications of taking and not taking antiretroviral therapy when you have a high CD4 cell count.
In general, this study -- together with others presented recently in the IAS meeting in Buenos Aires and last antiretroviral conference -- support current treatment guidelines to not initiate HAART in persons with asymptomatic HIV infection until the CD4 level is less than 350. Acute infections are an important exception to this rule.
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