First we had “Hit early, hit hard.” Most people attribute this statement to David Ho, who wrote an editorial in the New England Journal of Medicine in 1995 entitled, “Time to hit HIV, early and hard.” (NEJM 1995; 333:450-1.) Dr. Ho recognized that even in asymptomatic patients there was tremendous viral activity and T cell turnover and that treatment could reduce virus. Dr. Ho reasoned that early treatment would support the body’s immune system, through the preservation of T cells. With the protease inhibitors we finally had effective therapy and we recommended treatment to nearly all our patients, even those with good T cell counts.
After six years of “Hit early, hit hard,” the recommendations for when to start an HIV-positive individual on antiretroviral therapy (ART) shifted toward waiting until the T cells were lower. The reasoning was that patients with stable T cell counts above 200 were not at particular risk for opportunistic infections. Further, the medications were onerous to take and were associated with side effects and long-term toxicities such as risk of body fat redistribution, diabetes or cardiovascular disease. 
In the last five years clinicians have been shifting back toward treating patients with higher T cell counts. Several large studies have supported this and current guidelines recommend treatment being offered to all HIV-positive patients with T cell counts less than 500. Some clinicians recommend treating any HIV-positive patient no matter what the T cell count is. In addition, the medications are much better tolerated these days, and the toxicity issues are not as prevalent with the newer ART regimens. You could say that we’ve really come full circle in this discussion, back to “Hit early, hit hard.”
Patients who have recently seroconverted, that is, those who have recently become HIV positive, offer an interesting subset of patients. At the immediate time of seroconversion the amount of virus circulating in the blood is very high. This level falls over the next weeks to months and eventually settles at what is known as the “viral set point.” This level corresponds to a period of clinical latency for most patients and can last for several, sometimes many, years. The factors determining the viral set point and the length of time of clinical latency have not yet been fully discovered. It would be great to know why one person’s disease progresses much more rapidly than another’s and the answer is based on both the individual’s immune function and on viral factors, but there is a lot we still do not understand. Similarly, it’s been wondered if these recent seroconverters should be treated earlier or if treatment should be held, given the possibility of years of latency without the need for medications.
A recent study (The Setpoint Study, JID 2012:205 (January 1)) looked at two groups of recent seroconverters. One group received immediate treatment (within six months of serconversion) and one group did not. After 36 weeks of treatment the medication in the first group was stopped and both groups were followed for another 36 weeks. After 72 weeks 50% of the group who hadn’t received early treatment had T cells at a level requiring ART whereas in the immediate treatment group only 10% of the group met the requirements for starting ART. It seems the immediate treatment group had slowed down the disease progression. Because we don’t typically stop therapy in a patient who has started ART it’s not entirely clear how to translate these results into clinical practice. It does, however, further reinforce David Ho’s motto. Treating earlier, with effective therapy, can benefit the immune system.
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