U.S.
HIV treatment guidelines were recently updated to recommend that people with
HIV should start antiretroviral therapy when their CD4 cell count falls below
350 cells/mm3. However, evidence continues to accumulate suggesting that earlier
treatment may lead to better outcomes.
In a study published in the April
23, 2008 issue of AIDS, researchers with the Terry Beirn Community Programs for
Clinical Research on AIDS (CPCRA) conducted a study to examine the association
between CD4 cell count and risk of AIDS and non-AIDS diseases.
As
effective anti-HIV treatment has dramatically reduced morbidity and mortality
associated with AIDS-defining opportunistic illnesses, more HIV positive people
are now developing diseases not traditionally classified as AIDS-related, such
as cardiovascular and liver disease.
The
SMART treatment interruption trial (also conducted by the CPCRA) showed that
in addition to opportunistic disease, the rate of serious non-AIDS heart, liver,
and kidney disease also increased among participants who interrupted therapy and
had higher viral load during follow-up, suggesting that continuing HIV replication
has detrimental effects even before the CD4 count falls into the traditional "danger
zone" below 200 cells/mm3.
Motivated by the SMART findings, the investigators
performed an analysis of 1397 participants in the CPCRA FIRST trial who initiated
antiretroviral therapy in 1999 and 2000. The researchers looked at CD4 counts,
HIV RNA levels, and rates of fatal and non-fatal AIDS-related illness and non-AIDS
cardiovascular, liver, and kidney disease and non-AIDS-defining cancers over a
median follow-up period of 5 years.
Results
•
Participants
who started treatment with more than 350 cells/mm3 reached a higher median level
after 32 months than those who started with 200-350 cells/mm3 or fewer than 200
cells/mm3 (666, 487, and 335 cells/mm3, respectively).
•
During 5 years
of follow-up, a total of 227 patients experienced an AIDS event.
•
During the
same period, 80 patients developed serious non-AIDS disease.
•
Rates of both
AIDS and non-AIDS disease declined as the latest CD4 count rose:
•
AIDS:
-
less than 200 cells/mm3: 13.8 events per 100/person-years;
-
200-350 cells/mm3: 2.0 per 100/person-years;
-
greater than 350 cells/mm3: 0.7 per 100/person-years.
•
Non-AIDS:
-
less than 200 cells/mm3: 2.1 events per 100/person-years;
-
200-350 cells/mm3: 1.7 per 100/person-years;
-
greater than 350 cells/mm3: 0.7 per 100/person-years.
•
After adjusting
for baseline factors and latest HIV RNA level, the risk of AIDS events fell by
44% for each 100 cells/mm3 increase in CD4 count (P < 0.01).
•
Likewise, the
risk of non-AIDS disease fell by 14% per 100 cells/mm3 increase (P = 0.01).
•
Older patients
were at higher risk for cardiovascular events and non-AIDS-defining cancers.
•
Participants
with hepatitis B or C coinfection were at higher risk for non-AIDS liver disease.
•
Black patients
were at higher risk for kidney disease.
Conclusion
"Higher
CD4+ counts on antiretroviral therapy are associated with lower rates of non-AIDS
diseases and AIDS," the study authors concluded.
They added that,
"These findings expand our understanding of the implications of HIV-related
immunodeficiency and motivate randomized studies to evaluate the effects of antiretroviral
therapy on a broad set of clinical outcomes at CD4+ counts greater than 350 cells/[mm3]."
"If
the potential reduction in non-AIDS risk as well as AIDS risk could be realized
through earlier initiation of antiretroviral therapy," they wrote, "the
public health benefit would be substantial."
University of Minnesota,
Minneapolis, MN; Hennepin County Medical Center, Minneapolis, MN; University of
California San Francisco, San Francisco, CA; Kaiser Permanente Northern California,
Oakland, CA; Wayne State University, Detroit, MI.
5/06/08
Reference J
Baker, G Peng, J Rapkin and others. CD4+ count and risk of non-AIDS diseases following
initial treatment for HIV infection. AIDS 22(7):841-848, April 23, 2008.
Results
"Higher
CD4+ counts on antiretroviral therapy are associated with lower rates of non-AIDS
diseases and AIDS," the study authors concluded.
