Pneumonia
caused by the fungal infection Pneumocystis jiroveci is the most prevalent opportunistic
infection in patients with AIDS.
Some
experts have recommended that people with HIV/AIDS
who require treatment for opportunistic infections (OIs) should defer antiretroviral
therapy until OI treatment is completed, due to the risk of drug interactions
and intensified additive side effects. But this appears to be a risky strategy,
according to a presentation at the 15th Conference on Retroviruses
and Opportunistic Infections this month in Boston.
Andrew Zolopa and
colleagues with the ACTG A5164 Study Group conducted a Phase IV (post-marketing)
strategy trial in which 282 patients were randomly assigned to receive either
immediate antiretroviral therapy upon study entry or deferred antiretroviral therapy
after acute OI treatment was completed (at least 4 weeks after study entry).
Most
study participants (85%) were men, the median age was 38 years, 37% were black,
36% were Hispanic, and 23% were white. Overall, they had advanced HIV disease,
with a median baseline CD4 cell count of 29 cells/mm3; most (90%) had not previously
taken any antiretroviral drugs. Participants were stratified by CD4 cell count
(< or > 50 cells/mm3). The study provided lopinavir/ritonavir (Kaletra),
d4T (stavudine, Zerit), and tenofovir/emtricitabine
(Truvada), but clinicians were
free to prescribe any standard antiretroviral regimen they deemed appropriate.
Patients
were also stratified by OIs. The most frequent infections were Pneumocystis
pneumonia (63%), cryptococcal meningitis (16%), and bacterial infections such
as pneumonia or sepsis (12%); these bacterial infections are not "classical"
OIs, but occur more often in people with AIDS and were regarded as OIs for the
purposes of this study. About one-third of patients had more than one infection.
Individuals with tuberculosis were excluded, since there was insufficient information
about antiretroviral and anti-TB drug interactions when the trial began, as were
patients with OIs with no proven treatment.
At 48 weeks, the investigators
assessed rates of AIDS progression or death; no AIDS progression but continued
HIV viral load of 50 copies/mL or greater; or no AIDS progression with HIV suppression
below 50 copies/mL.
Results
•
The immediate and deferred arms started antiretroviral
therapy a median of 12 and 45 days, respectively, after initiating OI treatment.
•
There were no significant differences in initial
antiretroviral regimens in the 2 arms.
•
There was no statistically significant difference
in the immediate and deferred arms with regard to:
•
Rate of AIDS progression or death: 14% vs
24%, respectively;
•
No progression with detectable viral load:
38% vs 31%;
•
No progression with HIV suppression: 48% vs
45%.
•
Both arms achieved similar viral load reductions
and CD4 cell gains by week 24.
•
However, the immediate antiretroviral therapy
arm had:
•
Fewer cases of AIDS progression or death;
•
Longer time to AIDS progression or death (hazard
ratio 0.51);
•
More rapid achievement of a CD4 count above
50 cells/mm3 (median 8 vs 4 weeks) and above 100 cells/mm3 (median 12 vs 4 weeks).
•
There was a trend toward changing antiretroviral
therapy earlier in the immediate arm, but this did not reach statistical significance
(P = 0.15).
•
There were no significant differences in rates
of severe (grade 3 or 4) adverse events, treatment adherence, or frequency or
length of hospitalization.
•
The rate of immune reconstitution inflammatory
syndrome was also statistically similar, with 8 cases in the immediate arm and
12 in the deferred arm.
Conclusion
"Although
there was no significant difference between immediate and deferred antiretroviral
therapy in the primary endpoint that includes both clinical and virological response,
immediate antiretroviral therapy reduced death/AIDS progression over 48 weeks,"
the researchers concluded.
The reduced frequency of AIDS progression and
death in the immediate antiretroviral therapy arm was especially pronounced during
the first 6 months, and the more rapid increase in CD4 cell count reduced the
"window of vulnerability" to disease progression and death, the researchers
suggested.
They added that, "This randomized strategy trial suggests
that, absent contraindications, consideration should be given to early use of
antiretroviral therapy in HIV-infected patients presenting with an acute opportunistic
infections."
Stanford Univ, Palo Alto, CA; Statistical and Data
Analysis Ctr, Harvard School of Public Health, Boston, MA; Univ of Southern California,
Los Angeles, CA; Frontier Sci & Tech Research Fndtn, Buffalo, NY; Univ of
the Witswatersrand, Johannesburg, South Africa; Social & Sci Systems, Silver
Spring, MD; Univ College Dublin, Ireland.
2/26/08
Reference
A Zolopa, J Andersen, L Komarow, and others. Immediate vs Deferred ART in the
Setting of Acute AIDS-related Opportunistic Infection: Final Results of a Randomized
Strategy Trial, ACTG A5164. 15th Conference on Retroviruses and Opportunistic
Infections (CROI 2008). Boston, MA. February 3-6, 2008. Abstract 142.
Delaying
HAART during Opportunistic Infection Treatment Leads to Disease Progression and
Death
Results
