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Less
is More? STI in Acute and Chronic HIV-1 Infection [Altfeld
M and Walker BD Nature Medicine; 2001;7:881] The authors
provide a succinct summary of the state of the art for structured
treatment interruption. The experience is divided into the use of
this tactic for acute vs. chronic infection due to the great differences
in outcome:
Acute
Infection
- The "Berlin
patient" did well after treatment interruption following acute
HIV infection [NEJM 1999;340:1683]. The authors provide
the three year follow-up, which shows that this patient still
has a viral load of less than 1,000 copies/ml, and it is often
below 50 c/ml at three years.
- The largest
published experience with STI for acute HIV infection is from
the authors. The initial study showed that 3 of 8 had virologic
control with a single STI [Nature 2000;407:523]. They now
report that the patient with the longest follow-up in this experience
continues to have virologic control at 18 months. After re-treatment
and a second STI in the remaining five, two have had response
with persistent virologic control. The interruptions were associated
with "strong enhancement in both the breadth and magnitude of
cellular immune responses to HIV."
Chronic Infection
- Most studies
are small in sample size and show that STI results in viral rebound
to pre-treatment levels despite enhancement of HIV specific immune
responses [AIDS 1999;13:F79; AIDS 2000;14:397; AIDS
1999;13:677; PNAS 1999;96:15109; JID 2000;182:766;
AIDS 2000;14:1357]. These studies also showed that STI
and virologic rebound was well tolerated and the viral load could
be successfully suppressed with re-treatment. An occasional exception
was patients who developed the acute retroviral syndrome [Ann
Intern Med 2000;133:430; Ann Intern Med 2000;133:435].
- Two studies
have shown that multiple cycles of STI may result in magnified
immune responses with lower viral loads after STI [AIDS
2001;15:F19; AIDS 2001;15:F29].
- The largest
ongoing study of STI in chronically infected patients is the Swiss-Spanish
Intermittent Treatment Trial which has 128 subjects given intermittent
STI based on virologic response. After 52 weeks, only 13 of 99
subjects have shown enhanced virologic control compared to baseline
at 12 weeks off therapy. The responders were patients who generally
had low baseline viral loads.
The authors conclude
that the immune system can be mobilized to better control HIV replication
with STI, but there seems to be great variation in the success of
this treatment depending on acute vs. chronic HIV infection and,
in the latter group, the baseline viral load. This is still regarded
as experimental and should be restricted to clinical trials.
posted
11/9/2001
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