Lack of HAART and Low CD4 Cell Count Are Linked to Non-AIDS-related as well as Opportunistic Conditions

By Liz Highleyman

It is well known that combination antiretroviral therapy can halt CD4 cell decline and dramatically lower the risk of opportunistic infections (OIs) associated with impaired immune function.

Evidence continues to accumulate suggesting that uncontrolled HIV replication and declining CD4 counts are also linked to other types of conditions not traditionally considered AIDS-related. In the large SMART trial, for example, people who interrupted treatment when their CD4 count fell below 350 cells/mm3 not only had a higher risk of OIs and death, but also had more heart, liver, and kidney disease.

In a study described in the October 15, 2008 issue of Clinical Infectious Diseases, Richard Moore of Johns Hopkins School of Medicine and colleagues assessed the incidence of comorbidities considered "not related to HIV infection or AIDS" according to CD4 cell count and use of HAART.

The analysis included 2824 patients seen at the Johns Hopkins HIV clinic between 1997 (the very early HAART era) and 2006, representing 9172 person-years of longitudinal data. About 66% were men, 75% were African American, 23% were non-Hispanic white, 41% were injection drug users (IDUs), and the mean age was 38 years.

Looking at medical records over this period, the investigators assessed rates of hospitalization for serious cardiovascular, liver, gastrointestinal, kidney, pulmonary (lung), and neurological events typically considered non-AIDS-related or non-HIV-related. They also looked at non-AIDS-defining cancers (all types besides Kaposi sarcoma, non-Hodgkin's lymphoma, and cervical cancer due to human papillomavirus).

Results

• 817 cases of serious non-AIDS-related disease occurred in 679 patients during the study period:

• Cardiovascular: 206 events;
• Liver or gastrointestinal: 185 events;
• Kidney: 168 events;
• Pulmonary: 90 events;
• Neurological: 58 events;
• Non-AIDS malignancies: 110 events.

• The incidence of comorbidities not related to HIV infection or AIDS decreased as CD4 cell count increased.

• Use of HAART was associated with a significantly decreased incidence of comorbidities not related to HIV or AIDS.

• Among patients with a CD4 count below 200 cells/mm3, not using HAART approximately doubled the risk of non-AIDS-related illnesses (2.7 vs 1.2 cases per 100 person-years).

• Among those with fewer than 350 cells/mm3, those not taking HAART also were more likely to experience non-AIDS-related comorbidities (1.3 vs 0.6 per 100 person-years).

• There was a trend toward more non-AIDS-related illnesses in untreated individuals with a CD4 count above 350 cells/mm3 (0.8 vs 0.5 per 100 person-years), but the difference did not reach statistical significance.

• Regardless of CD4 count, older individuals (those over age 50), black patients, and IDUs were more likely to develop non-AIDS-related comorbidities.

"[T]his analysis provides evidence from clinical practice that HAART use is associated with a decreased risk of comorbidities not related to HIV infection or AIDS among patients with a CD4 cell count < 350 cells/mm3," the study authors concluded. "HAART may have a protective effect on the occurrence of comorbidities not related to HIV infection or AIDS and may reduce the risk of AIDS-defining illness."

The results from this study add to the evidence that ongoing HIV replication has deleterious effects well before the CD4 cell count falls into the OI "danger zone" below 200 cells/mm3. Some investigators believe so-called "non-HIV-related" comorbidities may in fact be due to chronic inflammation caused by HIV infection itself.

These findings support the recommendation for early antiretroviral therapy. The latest U.S. and European treatment guidelines advise initiating HAART when the CD4 count falls below 350 cells/mm3, but a growing number of experts think starting even sooner might be better.

10/3/08

Reference
RD Moore, KA Gebo, GM Lucas, and others. Rate of comorbidities not related to HIV infection or aids among HIV-infected patients, by CD4 cell count and HAART use status. Clinical Infectious Diseases 47(8): 1102-1104. October 15, 2008. (Abstract).