HIV clinic improves medication adherence 

DOT is latest experimental strategy

HIV clinicians treating patients who are failing their antiretroviral drug regimens face a conundrum: How do you increase adherence to increasingly difficult medication regimens among a population that has developed drug resistance most likely due to poor adherence in the first place?

"It is a challenging task," says Kathleen Squires, MD, associate professor of medicine at the Keck School of Medicine, University of Southern California (USC) in Los Angeles, and the medical director of the Rand Schrader Clinic in Los Angeles.

"With treatment-naïve patients, it won’t be as big a problem because now we can give once-a-day regimens," she adds. "But we do have a group of patients who harbor drug-resistant virus."

Medications have failed many treatment-experienced patients, perhaps because of toxicities or challenging regimens that caused patients to skip dosages, eventually leading to the development of drug resistance, Squires explains.

When this happens, it’s up to HIV clinicians to repair what’s broken.

"It’s a challenge for clinicians to tell patients, If you take this drug regimen, there is a reasonable possibility we can get somewhere; and that will translate to a better outcome for you in the long run,’" she continues. "But HIV infection is complicated to begin with, and for people who are dealing with other issues in their lives and dealing with viral loads and replication, it’s difficult."

HIV clinics can assist physicians with the task of improving adherence through a variety of strategies, including becoming involved in clinical trials designed to study HIV treatment adherence, Squires suggests.

"One of the main things we do for adherence and to make a full range of drugs available is we participate and collaborate with a number of groups on clinical trials to make those available to our patients," she says.

For example, the Rand Schrader Clinic, which treats about 3,000 HIV patients, has been involved in three studies of directly observed therapy (DOT) for HIV patients, Squires notes. Results from the studies soon will be available, she adds.

"If it looks successful, that would be expensive to incorporate in a clinic," Squires says. "But if it looks successful, we’ll apply for funding to incorporate that into our clinic."

Various strategies employed

The DOT, as demonstrated in one study, had two part-time employees who recruited 100 patients for the study, randomizing patients to one standard of care arm or to the DOT arm, she explains.

"It was arranged that either the patient would come into the clinic once a day to take one dose and then take the other dose home with them, or the worker would go out to the patient’s home," Squires says. "It was negotiated between the worker and the patient because some patients are reluctant to have people come to their homes."

At the time the trial began, there were no once-per-day HIV regimens, so patients were placed on drugs that had to be taken at least twice a day, she adds.

"Before the once-a-day regimens, the hope was that if you engaged a person in the DOT program, you are talking to them about the principles of why they need to take the drugs; and as the patient is having some success, this could be a positive experience to encourage adherence," Squires says.

DOT and modified DOT have been shown to have positive clinical outcomes in previous studies, including resulting in reducing HIV viral loads, decreasing opportunistic infections, and decreasing deaths from AIDS.1-3

However, at least one study of modified DOT found that while this adherence strategy improved health and virologic success among a population of HIV patients who had very low rates of adherence (from 40% to 70%), it also increased the rate of new drug-resistant mutations. The study assumed that modified DOT improved adherence to 90% of prescribed doses.3

Now that once-per-day regimens are available, it’s possible to tie DOT with other medical programs, such as drug-treatment programs for injection drug users, who could be observed taking their antiretroviral medications while they are receiving drug treatment, Squires notes.

Several studies have demonstrated success in using DOT with substance users and injection drug users, including HIV patients who are involved in a DOT program of coadministered methadone and HIV antiretroviral therapy.4-6

"It’s more possible to envision how you could do DOT on a longer-term basis," she says.

The Rand Schrader Clinic also improves adherence through the use of case managers who meet patients to discuss adherence and obstacles to taking antiretroviral drugs, Squires says.

"Patients are seen every three months by teams if they are doing well," she explains. "If they are failing their regimens, then they’re seen as often as needed to devise a new regimen for them."

Another adherence strategy is to use the USC School of Pharmacy students, staff pharmacists, and pharmacologist to help patients in the drug optimization clinic, Squires says.

"They see patients who are failing their drug regimens to see what’s going on in the individual patient’s case," she says. "Are they not taking drugs because they can’t tolerate side effects, or is it a problem with absorbing the drug and so forth?"

The patient’s individual needs are assessed, and staff help the patient better manage his or her antiretroviral therapy, Squires adds.


1. Foisy MM, Akai PS. Pharmaceutical care for HIV patients on directly observed therapy. Ann Pharmacother 2004; 38:550-556.

2. Harwell JI, Flanigan TP, Mitty JA, et al. Directly observed antiretroviral therapy to reduce genital tract and plasma HIV-1 RNA in women with poor adherence. AIDS 2003; 17:1,990-1,993.

3. Kagay CR, Porco TC, Liechty CA, et al. Modeling the impact of modified directly observed antiretroviral therapy on HIV suppression and resistance, disease progression, and death. Clin Infect Dis 2004; 38 Suppl 5:S414-420.

4. Conway B, Prasad J, Reynolds R, et al. Directly observed therapy for the management of HIV-infected patients in a methadone program. Clin Infect Dis 2004; 38 Suppl 5:S402-B.

5. Macalino GE, Mitty JA, Bazerman LB, et al. Modified directly observed therapy for the treatment of HIV-seropositive substance users: Lessons learned from a pilot study. Clin Infect Dis 2004; 38 Suppl 5:S393-397.

6. Clarke S, Keenan E, Ryan M, et al. Directly observed antiretroviral therapy for injection drug users with HIV infection. AIDS Read 2002; 12:305-307,312-316.