Durban World AIDS Conference
Wednesday, July 12
Durban, South Africa
Reported by Jules Levin
Report 16
Today
there was an amazing sight in front of the convention center. There was a group
of about 10 Africans doing a tribal dance in full garb
holding signs promoting traditional or alternate therapy. Many bystanders
were watching and taking pictures. Wish I had my camcorder with me. Most people
I speak with believe that Mbeki has said he doesn't deny that HIV causes AIDS.
ABT-378
In Treatment NaÔve: 72 week Update
100
treatment naÔve individuals were randomized to receive 1 of 3 dose levels of
ABT-378/r (200/100 mg BID), 400/100 mg BID or 400/200 BID), together with d4T
and 3TC given either from study entry (group 2) or after 3 weeks (group 1).
Enrollment into group 2. Enrollment into group 2 began following an evaluation
of preliminary efficacy & safety in group 1. After 48 weeks, all patients
began coversion to open label ABT-378/r (Kaletra) 400/100 BID dosing. Plasma
viral load was measured using Roche Amplicor Monitor 400 copy/ml assay, and
Abbott Labs quantiative 50 copy/ml assay.
At
baseline, there were 32 individuals in group 1--30 men, 2 women; 69% Caucasian,
28% Black, 3% Hispanic. Median viral load was 5 log (100,000 copies/ml) (range
3.7 log-6.0 log). Mean CD4 count was 421. In group 2 (n=68), 2 were women; 63%
Caucasian, 29% Black, 7% Hispanic. Viral load was 4.9 log (79,000 copies/ml)
(range 3.3 log to 6.7 log; 2000 copies/ml to 500,000 copies/ml). Median CD4
count was 301.
VIRAL
LOAD SUPPRESSION
On
Treatment Analysis: 93% (25/27) in
group 1, and 100% (57/57) in group 2 had <400 copies/ml
Intent-To-Treat
Analysis (missing values considered as treatment failures): 78%
in group 1 (25/32), and 84% (57/68) in group 2 had <400 copies/ml
On
Treatment Analysis: 96% (26/27) in
group 1, and 96% (54/56) in group 2 had <50 copies/ml
ITT: 81%
(26/32) in group 1, and 79% (54/68) in group 2 had <50 copies/ml
ABT-378
performed the same, using the 400 copy assay, whether a person's viral load was
<100,000 copies/ml or >100,000 copies/ml. There was no data on performance
regarding <50 when a person was less than or greater than 100,000 copies/ml.
Patients
with baseline viral load >100,000 copies/ml generally took longer to reach
<400 copies/ml than patients with <100,000 copies/ml, but response rates
were the same by week 20 and subsequently. At week 72, those with <100,000
copies/ml 100% had <400 copies/ml at week 72 by on treatment analysis, and by
ITT 78% had <400 copies/ml. For those with >100,000 copies/ml at baseline,
95% had <400 copies/ml at week 72 by on treatment analysis, and 87% had
<400 copies/ml by ITT analysis.
Mean CD4
count increase was 304 in group 1 by week 72, and 240 in group 2.
Based on
patient reported dose interruptions adherence was reportedly 98% through week
72. The most common adverse events were diarrhea, nausea, and abnormal stools.
Abbott reported that at week 72, only one patient discontinued due to an adverse
event/lab abnormality related to study drug.
MOST
COMMON ADVERSE EVENTS & LAB ABNORMALITIES
| ADVERSE EVENTS+ | Group 1 | Group 2 |
| Diarrhea* | 19% (6) | 22% (15) |
| Nausea | 6% (2) | 19% (13) |
| Abnormal stools** | 19% (6) | 3% (2) |
| Asthenia | 9% (3) | 6% (4) |
| Headache | 9% (3) | 6% (4) |
| Vomiting | 3% (1) | 6% (4) |
| GRADE 3/4 Lab Abnormalities | ||
| Total Cholesterol (>300mg/dL) | 13% (4) | 15% (10) |
| Triglycerides (>750mg/dL) | 13% (4) | 12% (8) |
| AST/ALT (>5xULN)*** | 0% | 12% (8) |
| + adverse events of at "least moderate severity, and probable, possible or unknown relationship" to ABT-378 | ||
| *>3 stools/day | ||
| **£3 siools/day | ||
| *** 4/8 patients with AST/ALT elevations were seropositive for HBV surface antigen (HbsAg) or HCV antibody at baseline | ||
PATIENT
DISPOSITION- 13 patients discontinued at or before week 72: 1 due to AST/ALT; 4
for noncompliance, 3 lost to follow-up, 1 for personal reasons, 3 for adverse
event--lymphoma, hyperglycemia in diabetic patient, alcohol detoxification.