Patients With Lowest CD4 Nadir in the Past Lose More CD4s in This Study

This study recently reported at this conference talks about the risks of treatment interuptions. The patients in this study who had interruptions had about 1.5 years on HAART and 2.7 years on therapy with CD4s of on average 350 and an average HIV viral load of 600 copies/ml. The average interruption was 289 days. On average CD4s dropped to 241 and viral load increased to 150,000 copies/ml. The important information is that the study found that patients with the highest CD4s but the lowest nadir CD4s had the biggest CD4 drop. In other words, for example, if your lowest CD4 count ever (that's whay nadir means) was 50 but your CD4s went up to 1000 after starting HAART, these persons had the biggest loss in CD4s. So, if you had a low nadir you lost CD4s more quickly. 29 patients had at least 1 clinical event during the interruption and 4 had AIDS events.

Research into interruptions are ongoing and important. It's possible we may find that patients can take interruptions safely and have benefits like time off therapy and a reduction in side effects & toxicities. But, it is important to remember there are risks from taking an interruption. The risks depend on your personal situation. If your CD4s are low, such as 300, taking an interruption can place you at risk for an OI. If your CD4s are high, such as 1000, taking an interruption may have less risk. Also, your viral load is likely to go up during the interruption. In this study the average viral load went up from 600 to 150,000 copies/ml. This also can be risky. You may have trouble getting back down to undetectable if your viral load goes too high. However, we need research into this area to see if there are ways to take interruptions for certain individuals in specific situations without too much risk.

Another type of interruption being studies is using a vaccine to boost the immune system when a person's viral load is undetectable on HAART. It is hoped that the vaccine may improve the immune system enough to control HIV without therapy or better on therapy than with HAART alone. This research is receiving much attention. But so far we do not have enough information. You may have heard about the Merck vaccine which is being researched now for this purpose. We don't have any information on this study yet. Other companies are developing similar vaccines. But we do not yet know if this approach will work.

Immunological changes during treatment interruptions (TI): risk factors and clinical sequelae
     M Poulton 1 , CA Sabin 2 , M Fisher 1 1 Royal Sussex County Hospital, Brighton, and 2 Royal Free and University College Medical School, UK

Introduction:
Although the possible beneficial effects of HIV TIs remain unproven, many patients are stopping therapy. Studies have shown that there is a risk of significant falls in CD4 count when therapy is interrupted. Identification of risk factors for CD4 drops may inform treatment decisions.

Methods:
Patients who had interruptions of highly active antiretroviral therapy (HAART) lasting 2 months or more were identified. Data were collected on reason for stopping therapy, CD4 count and HIV RNA histories, drug therapy and clinical events.

Results:
Thirty-eight patients were identified. TI occurred a median of 2.7 (0.5–10.5) years after starting antiretroviral therapy and 1.5 (0.5–3.2) years after starting HAART. The duration of TI was a median of 289 (77–1036) days. Baseline TI RNA levels were undetectable in 18 (47%) patients. During TI there was a significant drop in CD4 count from 348 to 231 (P=0.0001) and CD4 percentage from 17.5 to 14% (P=0.0001) and a significant increase in viral load from 2.78 to 5.17 log ( P=0.0001). Those with higher baseline CD4 counts (P=0.0001), but lower nadir CD4 counts (P=0.04) prior to the TI had the largest drops.

For patients with sufficient data (n=24) the median rate of CD4 loss prior to HAART was 62.8 cells/µl per year. This was significantly correlated with the change in CD4 count over the TI (r=0.56, P=0.005). Twenty-nine patients had at least one clinical event during TI; in four this was an AIDS defining illness. No factors predicted the development of a clinical event.

Conclusions:
Treatment interruptions are accompanied by significant CD4 cell loss and associated disease progression. Individuals with lower nadir CD4 counts and more rapid CD4 cell loss prior to HAART are more at risk and should be fully informed of the potential risks of TIs.