Pharmacotherapy for HIV+ Stimulant Dependent Individuals

In 1996, the use of protease inhibitors and triple therapy known as HAART (highly active
antiretroviral therapies) became widespread in the United States for the treatment of HIV.
This changed the disease process from a relentless and progressive one to a chronic one,
with the resulting need to focus on issues related to adherence. Because of unique aspects
of viral resistance with HIV, an adherence rate of 95% or higher is required to minimize or
halt the progression of the disease (DeMasi et al., 2001; Gross, Bilker, Friedman, & Strom,
2001). Cocaine use and dependence has been found to have deleterious effects on HIV infected
individuals (Fiala et al., 2005) Cocaine use hastens disease progression, increases viral
loads and decreases CD4 counts(Arnsten et al., 2002; Baldwin, Roth, & Tashkin, 1998;
Hurwitz, ; Kapadia, Vlahov, Donahoe, & Friedland, 2005; Lucas et al., 2006; Roth et al.,
2002; Roth, Whittaker, Choi, Tashkin, & Baldwin, 2005) Cocaine use correlates with increased
"no show" clinic visits and decreased or no-adherence to HIV medications. (Hinkin et al.,
2007; Ingersoll, 2004; Palepu, Horton, Tibbetts, Meli, & Samet, 2004; Sharpe, Lee,
Nakashima, Elam-Evans, & Fleming, 2004) There appear to be multiple reasons for
non-adherence in this substance abusing population. Factors such as forgetting and running
out of medications have been implicated with substances such as crack cocaine and heroin.
(Ingersoll, 2004; Kerr et al., 2004)

A medication that decreases or ceases cocaine use potentially improves adherence at clinic
appointments as well as adherence to medication. In addition, it might indirectly decrease
the progression of the disease. Ondansetron, a serotonin type 3 receptor antagonist (5HT3),
at 4mg twice a day has been shown to have a greater rate of improvement in percentage of
participants with a cocaine-free week compared to placebo in cocaine dependent non HIV
infected treatment seeking individuals. (Johnson, B.A. 2006)

Ondansetron is FDA approved for chemotherapy induced nausea and vomiting, postoperative
nausea and vomiting and radiation induced nausea and vomiting. Ondansetron has shown
efficacy for nausea and vomiting in HIV infected individuals for palliation, as well as for
diarrhea due to cryptosporidium infection.(Currow, Coughlan, Fardell, & Cooney, 1997;
Gompels et al., 1993; Schworer, Hartmann, & Ramadori, 1994) Until recently, ondansetron's
cost was prohibitive. However, as a generic drug it has become more affordable. Among the
benefits of this drug is the qualitative benefits for HIV infected individuals with nausea
and diarrhea as well as cocaine dependence. HIV medications can cause nausea (M. O. Johnson,
Stallworth, & Neilands, 2003; M. O. Johnson et al., 2005; O'Brien, Clark, Besch, Myers, &
Kissinger, 2003; Reynolds & Neidig, 2002) and thus adherence might be improved with this
medication in cocaine using individuals. Ondansetron is well tolerated in HIV infected
individuals, and according to micromedex there are no known drug interactions with HIV
medications (Gompels et al., 1993)

Ondansetron has a mild adverse events profile. In studies with cocaine dependent individuals
who were not HIV infected, our group found that Ondansetron had fewer side effects than
placebo (B. A. Johnson et al., 2006). Also, in that same study, Ondansetron recipients
attended more sessions than those of placebo. Both of these factors make this drug an
appealing option for cocaine dependent HIV infected individuals.

Inclusion Criteria:

- HIV infected individuals who are cocaine dependent based on the Diagnostic and
Statistical Manual IV-R

- 18-64 years of age

- Ability to read and write in English

- Seeking treatment for cocaine dependence

- Drug of dependence screen or benzoylecgonine urine specimen (metabolite of cocaine)
positive within the 2 weeks prior to study medication administration

- If female, non-pregnant or breast feeding and willing to use acceptable form of
contraception including oral contraceptives, hormonal (levonorgestrel) or surgical
implants or barrier plus spermicide

- Liver function tests and Chemistries from CARECAST or by blood draw within the last 3
months that must show no disease of the kidney or liver that could result in altered
metabolism or excretion of the study agent. AST and ALT can be no greater than twice
the upper limit of normal

- An EKG that shows no clinically significant abnormalities including but not limited
to bundle branch blocks, bradycardia with heart rate less than 50, tachycardia with
heart rate greater than 105

Exclusion Criteria:

- Non-English speaking (As these individuals are filling out rating forms, the criteria
for exclusion is directly related to ability to read and process information in
English.)

- Inability to process and sign informed consent

- Pregnant or nursing or unwilling to use contraception if female

- Restrictions on use of other drugs or treatments: The following medications which are
established or theoretically have a drug-drug interaction include: Apomorphine
(established),Mesoridazine (theoretical), Pimozide (theoretical), Thioridazine
(theoretical), Acecainide (theoretical), Amiodarone (theoretical), Arsenic Trioxide
(theoretical), Azimilide (theoretical), Bretylium (theoretical), Dofetilide
(theoretical), Droperidol (theoretical), Enflurane (theoretical), Halothane
(theoretical), Ibutilide (theoretical), Isoflurane (theoretical), Isradipine
(theoretical), Sematilide (theoretical), Sotalol (theoretical)

- History of neuroleptic malignant syndrome

- Allergy to ondansetron

- Clinically significant cardiovascular abnormality (EKG) or history of arrhythmias