Over the past two years, guidelines for starting HAART have become gradually more cautious by suggesting that treatment be initiated later (lower CD4+ counts) rather than earlier (higher CD4+ counts) in the course of HIV disease. Before this change in guidelines, some PHAs began therapy at CD4+ counts that are higher than the presently recommended starting point (for the latest treatment guidelines, go to http://hivatis.org/trtgdlns.html). As a result of early therapy, these PHAs may have had huge increases in CD4+ counts. Some American PHAs who found themselves in this position decided to embark on a closely supervised drug holiday. We now report on this study.

Study details

Doctors collected data on 72 subjects with the following profile:

• 24 women, 48 men
• average age – 35 years
• average pre-HAART CD4+ count – 285 cells
• average pre-HAART viral load – 26,000 copies

Before starting their drug holiday, subjects had their viral load suppressed with HAART for an average of six months. All subjects stopped taking HAART for at least three months; the average length of time off HAART was 11 months.

Results – CD4+ cell counts

• At the time subjects interrupted therapy, the average CD4+ count was 554 cells.
• Three months after stopping therapy, the average count had fallen to about 400 cells.
• Eleven months after stopping therapy, the count had fallen further, to an average of 300 CD4+ cells. (This is about the level of their CD4+ count when they originally started taking HAART.)

Those subjects who interrupted therapy when their CD4+ counts were greater than 350 cells "tended to lose cells faster than those who stopped therapy when their CD4+ count was below the 350 cell level." Another factor that affected the decline in CD4+ counts was age — CD4+ counts declined faster in older PHAs than in their younger counterparts.

Life-threatening conditionsFour subjects whose CD4+ counts fell to fewer than 200 cells while off therapy developed the following complications:

• AIDS-related wasting – 1 person
• blood poisoning due to bacterial infection – 1 person
• PCP (Pneumocystis carinii pneumonia) – 2 people

According to the doctors' article, in PHAs whose viral load was suppressed with treatment, supervised drug holidays appear to be safe so long as CD4+ counts remain above the 200 cell mark.

Intermittent therapy

One of the strategies pursued in treatment interruption studies is intermittent therapy. They can be one week on therapy/one week off, or the periods may be longer. The results of this study have implications for intermittent therapy studies. If, as this study has found, the factor that best predicts the loss of CD4+ cells while off therapy is the number of cells gained during therapy, then perhaps the best time to initiate drug holidays are when CD4+ cell counts are high. In this way, the loss of cells while off therapy may be minimized.

The doctors acknowledge that their report probably reflects a "best-case scenario." By that they mean that only subjects who were able to discontinue therapy for at least three months were included in this study. Those subjects who had "large" decreases in CD4+ counts would have had to quickly resume therapy. The results of this study may not apply to PHAs with a different profile.

REFERENCE

Tebas P, Henry K, Monday K, et al. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: implications for intermittent therapeutic strategies. Journal of Infectious Diseases 2002 Sep 15;186(6):851-4.

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