HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA

Immune Suppression Increases the Risk of Both OIs and Non-AIDS-related Conditions

It is well known that HIV positive individuals with lower CD4 cell counts are at increased risk for developing AIDS-related opportunistic illnesses (OIs). New data presented at the recent 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles indicate that lower CD4 counts raise the risk of non-AIDS-defining conditions as well.

Researchers with the FIRST Study (CPCRA 058) looked at the association between fatal and non-fatal OIs and non-OI events and patients' latest CD4 cell count prior to these events. In this study, 1397 treatment-naive participants were randomly assigned to 3 types of antiretroviral therapy: NNRTI + NRTIs, protease inhibitor (PI) + NRTIs, or triple-class regimens.

Non-OI events included:

• Liver disease: cirrhosis or grade 4 liver enzyme elevation;

• Cardiovascular disease: myocardial infarction, stroke, or coronary artery disease requiring surgery

• Kidney disease: end-stage renal disease or renal insufficiency;

• Non-opportunistic cancers: all malignancies excluding non-Hodgkin's lymphoma and Kaposi's sarcoma.


Results

• Among the 1397 randomized subjects, the median baseline CD4 count was 163 cells/mm3, with an average increase of 238 cells/mm3 during follow-up.

• CD4 cell changes and OI rates did not vary according to type of regimen.

After 5 years of follow-up, there were 266 new AIDS-defining events and 166 non-AIDS-defining events:

- 86 cases of liver disease;
- 38 cases of kidney disease;
- 32 non-opportunistic cancers;
- 21 cases of heart disease.

• As expected, OIs occurred more often in subjects with detectable HIV viral loads and lower CD4 cell counts.

• The risk of non-OI events -- combined and individually -- was also lower among patients with higher CD4 cell counts.

• The risk of OIs declined more dramatically after starting HAART than the risk of non-OI events.

• Each additional increase of 100 cells/mm3 lowered the risk of OIs by 43% and the risk of non-OI events by 16%.

• Among patients with CD4 counts above 200 cells/mm3, non-OI events were more common than OIs.


Conclusion

"Higher latest CD4 count was associated with a reduced risk of non-[OI] events (liver, cardiovascular, renal, and cancer), though to a lesser degree than with [OI] events," the authors concluded. "These data suggest that treatment strategies minimizing the time spent at lower CD4 counts will prevent both non-[OI] and [OI] events."

Presenter Jason Baker suggested, however, that these findings may apply only to individuals who started therapy with low CD4 cell counts, as was the case for many of the FIRST participants.

These FIRST data support the findings of the SMART study, which found that both OIs and non-opportunistic liver, kidney, and heart disease were more common in the group receiving CD4-guided intermittent therapy, who spent more time at lower CD4 counts than patients receiving continuous therapy.

Univ of Minnesota, Minneapolis, MN; Hennepin County Med Ctr, Minneapolis, MN; Univ of California, San Francisco, CA; Kaiser Permanente, Oakland, CA; and Wayne State Univ, Detroit, MI.

Link to study abstract

04/10/07

Reference

J Baker, G Peng, J Rapkin, and others (Terry Beirn Community Program for Clinical Research on AIDS). HIV-related Immune Suppression after ART Predicts Risk of Non-opportunistic Diseases: Results from the FIRST Study. 14th Conference on Retroviruses and Opportunistic Infections. Los Angeles, California. February 25-28, 2007. Abstract 37 (oral).

*WM El-Sadr, JD Lundgren, J Neaton, and others (SMART Study Group). CD4+ Count-Guided Interruption of Antiretroviral Treatment. New England J Medicine 355(22): 2283-2296. November 30, 2006.












































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