The AIDS Clinical Trials Group, an offshoot of the National Institutes of Health, is conducting a series of second-line treatment studies in volunteers with significant viral loads despite nucleoside analog and, sometimes, protease inhibitor therapy. These are the largest such trials so far. The variety of second-line regimens tested in each trial is rather complicated. Regimens and the results now available, most of which were just presented at the 6th Conference on Retroviruses and Opportunistic Infections, are described in the table below.
Trial: ACTG 359
>6 months prior indinavir and viral load between 2,000 and 200,000.
N = 300 (N = 42 for the drug interaction substudy)
DLV increased total drug levels of SQV/RTV or SQV/NFV. ADV unexpectedly decreased DLV levels, causing a decrease in SQV
SQV, RTV, DLV, NFV all affect and are eliminated by cytochrome P450 liver metabolism. ADV is excreted by the kidney. Virologic and immunologic response data available this spring.
Trial: ACTG 364
Long-time NA experience (participants rolled over from ACTG 175 to ACTG 302/303 to ACTG 364).
Median entry VL = 21,000
Mean entry CD4 = 388
N = 195
2 nucleoside analogs, at least one new (d4T/3TC, d4T/ddI, ddI/3TC) + EFV, NFV, or EFV + NFV
% with VL <500, week 40-48:
2 NAs/EFV: 60%
Difference between nelfinavir arm and the efavirenz-containing arms was statistically significant but unexplained. Adherence issues?
Trial: ACTG 368
>2 months 3TC + either AZT or d4T and CD4 <250 (mostly rolled over from ACTG 320).
Mean entry VL = 16,000
Mean entry CD4 = 153
N = 283
A: IDV q8h/EFV ± ABC
B: IDV q12h/EFV ± ABC
ABC vs. placebo, % with VL <500, week 16:
IDV q8h vs. q12h, % viral load <500, week 48:
ABC vs. placebo: difference was nonsignificant.
IDV q8h vs. q12h: q8h significantly better.
Trial: ACTG 370
Rolled over from ACTG 306 with viral load >500.
Prior time on two NAs: 24 to 36 months
N = 105
ddI/3TC or d4T/3TC switched to AZT/3TC/IDV or AZT/DLV/IDV
AZT/3TC switched to d4T/DLV/IDV
% with VL <200, week 16:
AZT/3TC/IDV - 65%
No significant difference between arms, though trend to improved outcome by switching 3TC to DLV.
Trial: ACTG 372B
AZT/3TC/IDV failure (ACTG 320 roll over).
Median entry VL = 39,000
Median entry CD4 = 196
N = 94
ABC vs. NAs, % with VL <500, week 16:
NFV vs. placebo, % with VL <500, week 16:
ABC vs. NAs: difference was nonsignificant.
NFV was significantly better than placebo.
Trial: ACTG 398
VL >1,000 after >16 weeks of SQV, IDV, NFV or RTV
N = 460
APV/ABC/EFV/ADV + SQV, IDV, NFV or placebo
No data yet
18 month follow-up
Trial: ACTG 400
VL >1,000 after >16 weeks NFV
No prior NVP, DLV, EFV
N = 300
A. RTV/SQV/EFV/2 NAs
B. IDV/EFV/2 NAs
C. APV/EFV/2 NAs
D. IDV/APV/EFV/2 NAs
2 NAs = ddI or 3TC + AZT or d4T
No data yet
18 month follow-up
|ABC - abacavir|
ADV - adefovir
APV - amprenavir
DLV - delavirdine
EFV - efavirenz
IDV - indinavir
NA - nucleoside analog
NFV - nelfinavir
NVP - nevirapine
RTV - ritonavir
SQV - saquinavir
N - number of trial participants
PK - phramacokinetics
q8h - every eight hours
q12h - every 12 hours
VL - viral load