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| Foreword |
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In the last 20 years since the
first HIV case was described, remarkable progress has been
made in our understanding of HIV disease. Potent combination
regimens have now changed our perceptions about HIV infection,
from a death sentence to a chronic yet manageable infection.
HIV medicine is probably one of the fastest growing areas
in medicine. This abstract booklet presents some of the
key studies that were presented at the First International
AIDS Conference on HIV Pathogenesis and Treatment, held
in Buenos Aires, Argentina between July 8-11, 2001.
Studies presented at this conference attest to the durability
of viral suppression achieved with combinations containing
protease inhibitors such as indinavir (5 years), as well
as regimens containing efavirenz (3 years) and nevirapine
(1 year). Studies also show that nevirapine-based regimens
penetrate well into sanctuary sites such as cerebrospinal
fluid and semen and are associated with immune restoration.
Lastly, an important study discusses the importance of adherence
in predicting the outcome of antiretroviral therapy. |
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Indinavir
(IDV), Zidovudine (ZDV), and Lamivudine (3TC): 5-year follow-up
Gulick R, Mellors J, Havlir D et al |
Objective
To assess the durability of antiretroviral activity and
tolerability of IDV + ZDV + 3TC.
Methods
Ongoing follow-up of 33 patients originally randomized to
receive IDV 800 mg q8h + ZDV 200 mg q8h + 3TC 150 mg b.i.d.
in the Merck 035 trial, a study of HIV-infected adults with
> 20,000 HIV RNA copies/ml (PCR), 50-400 CD4 cells/mm3,
and > 6 months of prior ZDV without prior use of 3TC
or protease inhibitors.
Baseline Parameters
HIV RNA : 41,900 copies/ml
CD4 cell count : 133 cells/mm3
Results
Intent-to-treat analysis
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| Parameter |
Week 156 (year 3)
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Week 212 (year 4)
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Week 260
(year 5)
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| Number of patients with: |
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| HIV RNA < 500 copies/ml |
21/31 (68%)
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18/31 (58%)
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18/31 (58%)
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| HIV RNA < 50 copies/ml |
20/31 (65%)
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17/31 (55%)
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3/29
(45%)*
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| Change in CD4 count from Baseline (median,
cells/mm3) |
+230 (n=31)
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+208 (n=29)
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+252** (n=27)
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*2 and **4 patients did not have data
available for this time
point yet. |
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Conclusion
More than half of patients originally randomized to IDV
+ ZDV + 3TC suppressed viral load levels for up to 5 years.
In general, patients with durable virologic suppression
had viral load levels less than 50 copies/ml. Late treatment
discontinuations were primarily due to nephrolithiasis.
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3-Year
durability of response with an Efavirenz (EFV) - containing
regimen: 144 week follow-up of study 006
Tashima K, Staszewski S, Morales-Ramirez
J et al |
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Objective
Study 006 is a multicenter, open-label, randomized trial
comparing EFV + ZDV + 3TC, indinavir (IDV) + ZDV + 3TC
and EFV + IDV in PI-, NNRTI- and 3TC-naive HIV-positive
subjects.
Study Population
The Initial Cohort (n=450) was enrolled by September 1997
and the Extended Cohort (n=1266) by September 1998.
Methods
Response rates were determined by observed (on-treatment)
and intent-to-treat analysis (n=450). Kaplan-Meier estimates
were performed on the time to treatment failure, durability
of response and durability of virological response (n=1266).
Baseline Parameters
Viral load : 4.78 log10 copies/ml
CD4 count : 341 cells/mm3
Results
- On-treatment analysis
- Similar results were seen in the subset of patients
with baseline viral load >100,000 copies/ml
- Similar increases in CD4 count were noted for all
regimens
- Based on the Extended Cohort (n=1266), EFV + ZDV
+ 3TC was superior to IDV + ZDV + 3TC by time to treatment
failure, durability of response and durability of virological
response
Conclusion
EFV + ZDV + 3TC continues to provide greater and more
durable viral suppression than IDV + ZDV + 3TC through
3 years of follow-up.
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Final
12-month results from the COMBINE study: A randomized, open
multicenter trial comparing zidovudine + lamivudine plus
nelfinavir or nevirapine in naïve patients.
Podzamczer D, Ferrer E, Consiglio E et
al |
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Objective
To evaluate the efficacy and safety of two HAART regimens
in HIV-positive naïve patients.
Methods
Randomized, open, multicenter study comparing zidovudine
+ lamivudine (ZDV 300 mg/3TC 150 mg b.i.d.) with nelfinavir
1250 mg b.i.d. (ZDV + 3TC + NFV) or nevirapine 200 mg
b.i.d. (ZDV + 3TC + NEV) in 142 HIV-infected naïve
patients recruited between November 1998 and August 1999
from 12 hospitals. Efficacy was assessed by intent-to-treat
(ITT) (missing=failure) and on-treatment (OT) analysis.
Baseline Parameters
Mean CD4 count : 359 cells/ l
Mean viral load : 5.15 log10 copies/ml
One third of patients had viral loads >5 logs
20% had CD4 count <200 cells/ l
Results
Intent-to-treat (at 12 months)
- Both regimens were equally effective in the subgroup
of patients with baseline viral loads >5 logs.
- An increase of 173 CD4 cells/ l was observed in the
nelfinavir group, whereas an increase of 162 CD4 cells/
l was seen in the nevirapine group.
Conclusion
Our results suggest that a nevirapine-containing regimen
has at least similar efficacy to a protease inhibitor-containing
regimen of nelfinavir. Both regimens have an acceptable
tolerance. A simple 4-pill nevirapine-based regimen may
be an excellent option for HIV-infected patients who initiate
antiretroviral therapy.
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