ACTG Highlights

01 Clinical

* Substitute oral agents or parenteral agents with long half-lives for those requiring
frequent intravenous dosing.
* Where suitable treatments are available, document their efficacy for prophylaxis.
* Achieve the ultimate goal of preventing Ols by supplanting therapy with
prophylaxis.
As of May 1, 1990, the total number of active ACTG protocols was 86. Onethird of these trials addressed HIV-associated Ols. Approximately 12 new protocols for
Ols are in development. The highest priority has been assigned to the following protocols
and diseases:
1. Pneumocystis carinii pneumonia prophylaxis studies.
2. Treatment studies for Pneumocystis carinii pneumonia (PCP), including
aerosolized pentamidine, clindamycin plus primaquine, and dapsone plus
trimethoprim.
3. Cryptococcal meningitis treatment and prophylaxis studies, including fluconazole
and SCH39304.
4. Cytomegalovirus retinitis treatment studies, including foscarnet and oral agents
such as ganciclovir and FIAC.
5. Toxoplasmosis treatment studies.
6. Acute treatment for symptomatic, disseminated Mycobacterium avium
intracellulare.
TRP has developed a comprehensive framework of action for developing clinical
trials for PCP and CMV, two particularly important Ols. Studies have been designed to
answer specific questions that make possible a logical progression of trials that address
both acute therapy, initial and salvage, and prophylactic therapy. The following
accomplishments for PCP acute initial treatment studies illustrate this strategy. The ACTG
has:
* Completed and published the findings of a dose-ranging study of trimetrexate that
establlished the dose to be used in the phase III comparative trial.
* Demonstrated a slower response to aerosolized pentamidine compared with
trimethoprim/sulfamethoxazole in patients with mild to moderate PCP.
* Completed the first phase of a pilot study of a new combination--intravenous
clindamycin plus oral primaquine--for use in patients with mild to moderate PCP.
Twenty-one of 24 patients responded by day 7.
* Completed 75 percent accrual for the extension of the oral clindamycin plus
primaquine trial. These data will support the use of oral clindamycin plus
primaquine as one arm in a comparative study for patients with mild,
"ambulatory" PCP who can be treated from the outset on an outpatient basis.
In developing salvage therapies for PCP, the ACTG has:
Established and continues to manage the Treatment Investigational New Drug
(IND) for trimetrexate for patients intolerant to standard therapies for PCP.
* Established and continues to manage an open protocol for trimetrexate for patients
refractory to standard therapies.