News and Literature Reviews

• Resistance Testing for Na?ves is Cost-Effective
• HPV Vaccine in Phase III Clinical Trials
• A New Way to Prevent HIV?
• HIV/HCV Co-infected Liver Transplant Candidates
• Organ Transplants for HIV Patients

Resistance Testing for Na?ves is Cost-Effective

Utilizing a previously published model of HIV disease, Sax, et al, projected the long-term and clinical cost outcomes for a cohort of HIV-infected, antiretroviral (ARV)-na?ve patients who undergo pretreatment resistance testing. In the base case, the overall prevalence of ARV resistance among treatment-na?ve patients was 8.3%. Direct costs of treatment for both routine medical care and for acute illnesses were estimated from data from the AIDS Cost and Services Utilization Survey. In the absence of primary resistance testing, patients had a projected mean quality-adjusted life expectancy of 168.3 months and a total lifetime cost of $336,000. With resistance testing at the time of initial diagnosis, the mean quality-adjusted life expectancy increased to 169.3 months and total costs increased to $338,600. Study authors concluded that resistance testing at the time of HIV diagnosis is a cost-effective strategy that can lead to selection of a more effective initial ARV regimen and likely longer survival for patients who have drug-resistant virus.
Sax P, et al. Should resistance testing be performed for treatment-na?ve HIV-infected patients: a cost-effectiveness analysis. Clin Infect Dis. 2005; 41(9):1316-23.

HPV Vaccine in Phase III Clinical Trials

GARDASIL^TM, a quadrivalent human papillomavirus virus (HPV) type 6, 11, 16, 18 recombinant vaccine, has been evaluated in a Phase III study, titled FUTURE II. Over 12,000 women, aged 16 to 26 years, at 90 centers were randomized to receive a three-dose regimen of either GARDASIL or placebo at day 1, month 2 and month 6. Among women who received three doses of GARDASIL, 100% of high-grade cervical pre-cancers and non-invasive cervical cancers (CIN 2/3 and AIS) associated with HPV types 16 and 18 were prevented. Twenty-one cases of CIN 2/3 or AIS were observed in the placebo group. This trial is part of the ongoing phase III program for GARDASIL, which involves over 25,000 people in 33 countries worldwide.
Finn S, et al. Prophylatic quadrivalent human papillomavirus (HPV) (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine (GardasilTM) reduces cervical intraepithelial neoplasia (CIN) 2/3 risk. Oral abstract LB-8a. Infectious Diseases Society of America meeting. San Francisco, CA. October 7, 2005.

A New Way to Prevent HIV?

Vaginal microbicides, chemical substances that, when applied to the vagina before heterosexual intercourse, have the potential to prevent or reduce HIV transmission. The non-nucleoside reverse transcriptase inhibitor, TMC120, is one such HIV microbicide candidate currently being tested in Phase I clinical trials. In a recent study, Malcolm, et al measured the daily amounts of TMC120 released from silicone elastomer vaginal rings over a 71-day period. An average TMC120 daily release of 136 µg/day was determined by linear regression. Based on upper limits for the volumes of cervicovaginal fluid and semen, and assuming that the in vivo and in vitro release rates of TMC120 are similar, then the concentrations of TMC120 in the combined fluids are calculated to be within the range required to prevent HIV infection (.01 µM at 10 min, 1.1 µM at 1 hr, 13.2 µM at 12 hr). Study authors concluded that there is the potential for providing protection against HIV infection in the form of a female-controlled vaginal ring device.
Malcolm R, et al. Long-term, controlled release of the HIV microbicide TMC120 from silicone elastomer vaginal rings. Jour Antimicrobial Chemo. 2005; 56(5):954-6.

HIV/HCV Co-infected Liver Transplant Candidates

Liver disease is the leading cause of death for HIV/HCV co-infected patients. Despite equivalent Model for End-Stage Liver Disease (MELD) scores at the time of liver transplantation listing, HIV-infected patients demonstrate significantly shorter pre-transplantation survival time when compared with non-HIV-infected patients. Shorter pre-transplantation survival times among these patients are primarily associated with death related to infection. To improve the survival of the HIV/HCV co-infected liver transplant candidate, Stock recommends early referral of the co-infected patient for liver transplantation. Co-infected patients must meet the same standards as all liver transplant recipients, including a prolonged period of abstinence from alcohol and narcotics, sufficient rehabilitation and demonstration of social support. Additionally, co-infected liver transplant candidates must have CD4-T cell counts greater than 100, the absence of current opportunistic infections and documentation that HIV can be suppressed with an antiretroviral regimen. In the early experience of solid organ transplantation among HIV-infected patients, most transplant centers still determine transplant eligibility according to MELD scores. Unfortunately, by the time liver function deteriorates to a point where the MELD score is sufficiently high for transplant eligibility, HIV-infected candidates no longer meet the entry criteria applied by most transplant centers. Synchronized multi-special care combined with early referral will help to minimize the number of deaths among co-infected patients on liver transplant waiting lists.
Stock G. Rapid deterioration of HIV co-infected patients waiting for liver transplantation is not predicted by MELD. Liver Transplantation. 2005; 11(11):1315-17.

Organ Transplants for HIV Patients

AB228, authored by Assemblyman Paul Koretz and recently signed by California Governor Arnold Schwartzenegger, is the first bill passed by the California State Legislature that prohibits health insurers from denying coverage for organ transplants based solely on a patients' HIV status. Historically, HIV-infected patients have not been considered suitable candidates for organ transplantation due to their relatively shortened lifespan. However, antiretroviral therapy has greatly extended the life expectancy of these patients and studies have shown that organ transplants in qualified HIV-infected patients lead to similar outcomes when compared to non-HIV-infected patients.
California Political Desk. American Chronicle. September 29, 2005. Last accessed October 26, 2005 articleID=2665