• The QUEST Cohort: Treatment of Primary HIV Infection (PHI) With Quadruple HAART: Week 48 Preliminary Results (Poster 520)
  Authored by S. Kinloch, D. Cooper, F. Lampe, D. Smith, G. Janossy, B. Hoen, A. Sonnerborg, C. Tsoukas, A. Phillips, L. Goh, L. Perrin
  View the original abstract

The treatment of people who are diagnosed during primary HIV infection (PHI) remains a special situation. Many of them may not develop low CD4 counts for several years, yet early treatment offers a unique opportunity to influence the course of their disease. Over the past several years, work by Drs. Eric Rosenberg and Bruce Walker suggested that if treatment was started early in PHI and then structured treatment interruptions were performed, the immune response to HIV might be more robust and more broad, improving the body's ability to control the virus. This work is ongoing, but it is proving more complex than first thought (like everything else in HIV).

Early treatment studies in the Swiss Cohort led by Dr. Kinloch suggested that if patients started AZT (zidovudine, Retrovir) during PHI, they would achieve a lower viral set point and a higher viral load than if they waited until chronic disease. Optimistic studies at the Aaron Diamond AIDS institute, led by Marty Markowitz and David Ho, aggressively treated patients during PHI with HAART in the hopes of eradicating viral reservoirs, but the discovery of an additional reservoir in resting cells made it clear that this reservoir would be slow to drain.

This then is the background of the QUEST cohort. The object of this study was to find patients with PHI, treat them for 18 months with a four-drug regimen, then randomize them to an additional six months of HAART with or without vaccine. The patients will then stop therapy to assess viral control. This paper reports the effects of the first 48 weeks of the quad therapy.

The quad therapy chosen consists of Combivir (AZT+3TC), abacavir (ABC, Ziagen), and amprenavir (APV, Agenerase). The investigators enrolled 148 patients on three continents. By week 48, only 115 were available for follow up. Twelve had stopped therapy, 80 were still on four drugs, one was on five drugs, and 22 had decreased to "standard" three-drug regimens. Only 57 percent remained on the original regimen. This is consistent with another study of this four-drug (all Glaxo) regimen in chronically-infected patients which showed it to be fairly difficult to tolerate. Nausea was the most common significant side effect, perhaps due to the combination of APV and AZT. Perhaps the new prodrug of APV, fosamprenavir (or "908") which causes much less nausea, would have been better tolerated, but it was not available at the time the study was launched.

Nonetheless, among those who remained on therapy, the drops in viral load were impressive. The median drop in viral load was 5.3 log (about 3 million copies) but this was made possible by the very high baseline viral load during PHI and the use of an "ultra-ultra-sensitive" assay with a limit of detection of 3-10 copies. Of those on treatment, 69 percent were less than 10 copies and 50 percent less than 3, but the intent-to-treat results were less impressive.

Another question was whether aggressive early treatment would decrease cellular viremia. Messenger RNA (mRNA) and viral DNA were well suppressed. Of those on treatment, 56 percent had less no infected cells per million PBMC using an assay with a lower limit of 50 infected cells, and 12 percent were DNA negative at a cutoff of 3 per million.

The authors concluded that treated patients achieved a very high level of viral control as shown by viral RNA, mRNA, viral DNA and CD8/38+ cells. However, we will need to watch for the next phase of the study to really know what can be achieved long term.

So, if a person is diagnosed within four to eight weeks of infection, what should he or she do? I think the jury is still out, but it is a golden opportunity. Until we know for certain that we cannot improve the long-term prospects for control without drugs, my opinion is that if the person is willing and committed, treatment is a good idea. However, the ideal way to do this is in the context of clinical research, so we can eventually learn the right answer.

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