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HIV
Viral Load Response to Antiretroviral Therapy According to the Baseline
CD4 Count and Viral Load [Phillips AN et al. JAMA 2001;286:2560]
This is an
extraordinary study with data from the Swiss HIV Cohort, the Frankfurt
HIV Clinic Cohort, and EuroSIDA studies designed to determine the
relationship between viral load response to antiretroviral therapy
as correlated with baseline CD4 counts and baseline viral loads.
The study included 3,226 patients with a median follow-up of 119
weeks. The number who achieved viral suppression to <500
c/ml at 32 weeks was 2,741 (85%). Several observations are important:
- There was no
statistically significant difference in the frequency of achieving
viral suppression based on baseline CD4 cell count when comparing
the CD4 cell strata of <200, 200-350 and >350.
- There was no
statistically significant difference in the frequency of achieving
viral suppression based on baseline viral load when comparing
<10,000 c/ml, 10,000-100,000 c/ml or >1000,000 c/ml. However,
the time to achieve viral suppression at <500 c/ml was longer
in those with a higher baseline viral load.
- A subset analysis
of 609 patients who had the ultrasensitive viral load assay showed
that neither baseline CD4 cell count or viral load according to
the strata defined above showed a significant difference in the
rate of achieving viral loads below 50 c/ml at week 32.
- There were
changes in the initial regimen during the first 40 weeks in 1,329
(41%), but there was no difference in this frequency according
to baseline CD4 cell count or baseline viral load. These results
are summarized in the following tables:
| Baseline
CD4 Count |
VL
<500 at wk 32
N = 2637 |
VL
<50 at wk 32
N = 609 |
| <200/mm3 |
1014/1296
(78%) |
62% |
| 200
- 349/mm3 |
596/695
(86%) |
75% |
| >350/mm3 |
536/646
(83%) |
74% |
| Viral
Load at Baseline |
VL
<500 at wk 32
N = 2637 |
VL
<500 at wk 32
N = 609 |
| <10,000
c/ml |
263/335
(79%) |
71% |
| 10,000
- 99,999 c/ml |
815/968
(84%) |
74% |
| >100,000
c/ml |
1068/1334
(80%) |
62% |
Comment:
The history of antiretroviral treatment guidelines has had three
major shifts in recommendations for initiating therapy. The first
recommendation in the early 1980s was to use AZT monotherapy in high
dosage for those with an AIDS-defining diagnosis, meaning very late
in the disease process. The recommendations were changed in 1996-97,
when there was much excitement about the PI-based regimens and extraordinary
progress resulting from the use of HAART when the CD4 cell count was
<500/mm3.
Enthusiasm for therapy continues; however, enthusiasm for early
therapy has diminished, based on several observations:
- There are no controlled trials that have demonstrated any benefit
to early therapy. It should be noted there are also no studies
that specifically address this issue, so the only data are from
cohort studies such as this one that demonstrated no benefit to
treatment until the CD4 cell count is <200.
- Early therapy was previously advocated, in part due to the
presumption that HIV could be cured. We now know that this is
not a realistic expectation with the drugs that are currently
available.
- The disadvantages of treatment have become quite obvious: Side
effects, including many that were not perceived in 1996-97, a
rigorous requirement for adherence to regimens that are often
very complex, and concerns about the evolution of resistance.
- A confusing part of these analyses concerns the baseline viral
load and its role in determining therapeutic recommendations.
The MACS data showed a strong correlation between probability
of an AIDS-defining diagnosis with viral load levels that were
independent of the CD4 cell counts. Subsequent data have shown
that the CD4 cell count is the most important prognostic indicator,
and the role of the viral load is somewhat variable according
to study and conclusions about the threshold.
The conclusion from these studies is that where there appears
to be consensus regarding the appropriate CD4 cell count for initiating
therapy, the consensus is 200 cells/mm3.
There may also be enthusiasm for a subset of patients who have a
higher CD4 cell count when it is accompanied by a high viral load.
Patient readiness is another critical variable. Regardless of the
threshold, there is continuing emphasis on the need for aggressive
treatment when the decision has been made to start, and that means
at least three drugs for all patients with the current menu of agents.
posted
12/10/2001
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