ACTG 175 confirms the benefit of antiretroviral therapy in persons starting between 200-500 CD4 cells and before the development of AIDS (cf. ACTG 016, 109).
ACTG 175 shows for the first time that initiating antiretroviral therapy at this time (CD4 counts 200-500/mm3) can delay death as well as progression (cf. Delta).
ACTG 175 shows for the first time that ddl-containing regimens can improve survival as well as delay progression (cf. ACTG 116B/117).
ACTG 175 shows that for pre-AIDS patients with no AZT experience, clinical outcomes can be improved by starting with AZT+ddl, AZT+ddC or ddl alone as opposed to starting with AZT alone (cf. ACTG 152 in children
ACTG 175 shows that for pre-AIDS patients with AZT experience, clinical outcomes can be improved by switching to ddl monotherapy or to AZT+ddl combination therapy (cf. ACTG 116B/117) and that switching to AZt+ddC may not be clinically beneficial (cf. ACTG 155).
ACTG 175 shows that medium-term studies measuring clinical progression and survival are possible in intermediate-stage patients.
ACTG 175 did not have the power to distinguish which of the three alternative regimens (ddl alone, AZT+ddl, AZT+ddC) is optimal first-line or early second-line therapy.
The losses to follow-up in ACTG 175 were lower (19%) than in the higher CD4 stratum of ACTG 019 (35%), suggesting that it is possible to improve long-term follow-up still further.
ACTG 175 showed that there were no significant differences among the four treatments arms in adverse events, but 25% were lost to follow-up in the naive arm compared to 15% in the AZT-experienced arm, suggesting that up to a quarter of AZT-naive patients find the drug(s) unbearable even without displaying ACTG-graded toxicities.
ACTG 175 could not show any benefit to starting with combination therapy as opposed to monotherapy. This is because AZT monotherapy performed poorly, pulling down the overall “delayed” arm, while ddl monotherapy appeared equivalent to the two combination arms.
ACTG 175 shows that it is a mistake to rely on surrogate markers such as CD4 counts (and viral load) to establish the standard of care, since the group with the greatest CD4 cell rise (AZT+ddC) did no better clinically–and possibly worse–than the other two groups (AZT+ddl and ddl alone).
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