Research presentation poster by Tracy Swan and Lei Chou; winner of a Chairman’s Choice Award at the 2008 HIV DART conference “Frontiers in Drug Development for Antiretroviral Therapies.” The complete text is available online.
Populations in Preapproval Studies and Postmarketing Commitments, 2005–2008
| Women | 12% female |
| HBV/HCV coinfection | ~10% coinfected |
| Renal/hepatic impairment | Has not been studied in people with moderate or severe hepatic impairment or severe hepatic impairment. Renal clearance is negligible, therefore difference in clearance not expected or studied in persons with renal impairment |
| Postmarketing commitment |
Released from: methadone/buprenorphine interaction study; 48-week prospective observational diversity cohort study stratified by race and gender to assess efficacy and safety including potential risk parameters such as CD4 count and coinfection Pending: drug-drug interaction study of PEG-IFN alfa 2a and TPV/ritonavir; pharmacokinetics (PK) in HIVnegative persons with Child-Pugh class B liver disease; formal QT prolongation study |
| Women | ~10% |
| HBV/HCV coinfection | 12.4% |
| Renal/hepatic impairment | Studied in people with mild and moderate hepatic impairment Renal clearance is negligible, therefore difference in clearance not expected or studied in persons with renal impairment |
| Postmarketing commitment |
48-week study of ARV-experienced females to elucidate potential differences in safety and efficacy |
| Women | ARV experienced: ~12%; ARV naive: 20% |
| HBV/HCV coinfection | ARV experienced: HB V coinfected 6%; HC V coinfected ~9%; HBV/HCV <1%; ARV naive: 7% overall |
| Renal/hepatic impairment | Studied in people with moderate hepatic impairment and severe renal impairment |
| Postmarketing commitment |
48-week nonrandomized open-label, single-arm study in 200 people—at least 50% African American and at least 25% female—to characterize efficacy and safety of raltegravir in a population that closely reflects the U.S. HIV-infected population |
| Women | ARV experienced: ~11%; ARV naive: 30% |
| HBV/HCV coinfection | ARV experienced: Yes; number unspecified; ARV naive: ~13% |
| Renal/hepatic impairment | Not studied in people with hepatic impairment; studied in people with moderate renal impairment |
| Postmarketing commitment |
Conduct study of DRV/ritonavir in treatmentexperienced female patients to elucidate differences in efficacy and safety; drug-drug interaction study with buprenorphine/nalaxone |
| Women | ARV experienced: ~11%; ARV naive: 29% |
| HBV/HCV coinfection | ARV experienced: 6% HB V coinfected; 6% HC V coinfected; ARV naive: unknown |
| Renal/hepatic impairment | Not specifically studied in renal impairment or sufficiently studied in hepatic impairment |
| Postmarketing commitment |
Study in coinfected people including people with Child-Pugh class C; assess effect of renal impairment on maraviroc PK at a dose of 150 mg combined with a boosted protease inhibitor (in people with mild to moderate renal impairment) and 300 mg alone (in people with severe renal impairment and on dialysis) |
Ongoing Underrepresentation
The underrepresentation of women, people of color, and drug users in clinical trials for AIDS/HIV has been an ongoing concern for HIV treatment activists, who routinely push the pharmaceutical industry and the public research networks to enroll trial populations that are representative of the actual HIV demographics in the United States. According to recent Centers for Disease Control and Prevention data on U.S. HIV prevalence, women constitute approximately 25% of those with HIV infection; African Americans, a staggering 46%; Hispanics, 17%; and injection drug users, 18%. All of these populations are typically underenrolled in HIV clinical trials.
Swan and Chou’s presentation focuses on the clinical trials of five recently approved antiretroviral (ARV) drugs and highlights the sharp contrast between the demographics of the trials’ participants and the demographics of the U.S. epidemic. Their study notes that “insufficient enrollment of special populations—an umbrella term for women, people of color, and people with common comorbid conditions, such as renal impairment and viral hepatitis—has led FDA to request postmarketing commitments (PMCs) for five recently approved antiretroviral agents.”
The authors conclude with these key points:
- Preapproval trials can address concerns usually dealt with in postmarketing commitments, through diverse enrollment and a more thorough portfolio of pharmacokinetic and drug-to-drug interaction studies.
- Regulators need larger, more tempting carrots and sharper sticks to prompt more thorough premarketing studies, and prompt initiation of postmarketing commitments.