Highlights from Recent Conferences -- HIV Viral Load, Resistance Testing, and Adherence

Harvey S. Bartnof, MD

Drug Resistance Testing May Improve Outcome

• Access to drug resistance testing may improve HIV viral load outcome, but trial results provide conflicting data.

Although there are several commercially available HIV drug resistance tests, none are yet approved by the Food and Drug Administration (FDA). While these tests have improved in the last year or so, their reproducibility is still in question. The tests are also extremely expensive. There has been controversy within the HIV/AIDS research community as to whether resistance testing results would enhance clinical outcome, that is, whether use of the tests would lead to a longer time before HIV viral load detection or increase in people taking HAART. Many ongoing trials are attempting to answer this very question. The interim results of two different studies reported recently yielded opposite results, underlining the lack of a clear answer in this area.

In a late-breaker session at the Glasgow meeting, researchers from the Archet Hospital in France presented interim data suggesting some clinical benefits from using genotypic resistance tests. A total of 108 participants were enrolled in a trial after their combination anti-HIV regimens failed. All were moderately treatment-experienced. After drug failure, a new drug combination was prescribed by the physician based on the clinician's judgment plus either clinical guidelines or the results of HIV genotypic resistance testing. Genotypic testing measures the specific gene mutations in a person's HIV strains.

An interim analysis was done after six. The results indicated a significantly greater decrease in HIV RNA viral load for the genotypic testing group compared to the clinician judgment/guidelines group. Access to genotypic resistance testing results led to a mean decrease in viral load of 1.1 log copies/mL, compared to a decrease of only 0.4 log copies/mL without such test results. Initial decreases in HIV viral load have been linked with a more favorable sustained viral load outcome. This and several other studies of resistance testing are currently ongoing. The results of such trials would have to indicate significant clinical benefit before third party payers are likely to reimburse for the tests.

In contrast to the French study, researchers from the Centers for Disease Control and Prevention (CDC) found that using genotypic resistance testing was not associated with an improved outcome for a group of 96 participants whose antiretroviral therapy was failing. This study was somewhat less rigorous due to its being a historical study. Successful modification of the anti-HIV regimen after 3-12 weeks included adding at least two new drugs, adding a drug from a previously unused class of agents, and adding any new NNRTI.

Durant, J. and others. Can HIV genotype determination be useful for individualized adaptation of antiretroviral therapy?: the French Viradapt study. 4th ICDTHI. Abstract OP7.1

Weidle, P.J. and others. Factors associated with the successful modification of antiretroviral therapy. 36th IDSA. Abstract 445Sa.

Early Viral Load Response May Predict Later Response

• Viral load response at 8-12 weeks may predict response at one year.

Approximately half of patients started on HAART do not achieve an undetectable viral load at one year, using a test with a limit of quantitation of 500 copies/mL. Researchers have attempted to determine whether earlier viral load response could predict undetectable viral load at one year. Then, perhaps, those whose regimen was predicted to fail at one year could change therapy earlier in another attempt to achieve an undetectable viral load.

Julio Montaner, MD, and colleagues from the AIDS Research Program in Vancouver analyzed results from 355 participants enrolled in the AVANTI 2, AVANTI 3, and INCAS trials. They found that the plasma viral load as early as twelve weeks after starting HAART was a very good predictor of outcome at one year. However, the best predictor was the viral load at 28 weeks.

A separate report on this topic was authored by researchers from the Instituto di Salud Carlos III in Madrid. A total of 100 participants were included in their study. The researchers found that the HIV plasma viral load level after three months predicts the viral load outcome at one year. They suggest that therapy intensification (adding new anti-HIV drugs) should be investigated at the third month of therapy for persons not achieving a viral load below 50 copies/mL.

De Mendoza, C. and others. Rate of rebound in plasma viremia and emergence of drug resistance at one year in patients achieving < 50 copies/mL compared to those having 50-500 copies/mL at the 3rd month of being under HAART. 4th ICDTHI. Abstract P120.

Montaner, J.S. and others. How early can we predict 52 week virologic success in antiretroviral naive patients? 4th ICDTHI. Abstract OP6.2.2.

Volberding, P. Case presentation: clinical management issues in antiretroviral-experienced patients. Current Challenges in HIV Disease Conference. International AIDS Society-USA. October 28, 1998.

High HIV Viral Load Linked to Poor Adherence

• Non-adherence is linked with the development of drug-resistant HIV strains.

An interesting report regarding adherence was presented by researchers from the Collaborations in HIV Outcomes Research-U.S. (CHORUS) team. CHORUS is a large observational database from four U.S. urban locations. The analysis included 1,616 persons with HIV/AIDS, including 8% women, 13% African-Americans, and 7% Hispanics.

The main finding of the report was a significant association between detectable HIV RNA viral load and non-adherence to therapy, as reported by HIV positive participants. The study design did not allow the authors to conclude whether persons with detectable viral loads may be less adherent, or whether poor adherence leads to disease progression with viral load increases. Stated another way, the "chicken or the egg" question applies: which came first, non-adherence or high viral load? The results indicate either that sicker patients are more likely to miss doses of their anti-HIV therapy, or that those patients who missed doses of their medication are more likely to have detectable HIV viral loads.

Berge, J. and others. Relationship between demographic and clinical disease characteristics and medication adherence among patients in CHORUS. 38th ICAAC. Abstract I-212.

Adherence Benefits with Two-Way Pagers

The most common reason for people to miss a dose of medication is, "I forgot". A few reports have indicated that using timer devices can help remind people not to forget a medication dose. These may include wristwatch alarms and standard pagers ("beepers"). Now, researchers from the University of Washington in Seattle have reported improved adherence using two-way, interactive alphanumeric pagers. These pagers can print letters in addition to numbers. There is also a device that allows the person with the pager to immediately respond by pressing a button that correlates with a message or choices on a menu.

The experimental trial included twelve participants who used the pagers for three months or longer. Paging programs were individualized based upon the person's anti-HIV regimen. The paging mechanism was delivered by a computer and modem-based system. The computer kept a record of all outgoing pages and responses by the participants. People were reminded of medication doses, times, food requirements, and fluid needs. They were also asked about missed doses and side effects.

The results showed that 83% of the participants used the device for the full three months. Satisfaction with the system was high. Two people stopped due to "technical problems." An average of 38 pages were sent to each participant each week. Participants responded to 87% of the questions sent to the pager, with average response times of 4-21 minutes. When asked about side effects, 29% indicated that they had experienced at least one. When asked about missed doses in the previous 24 hours, 8% indicated a missed or late dose.

The advantages of this system are many, even considering the expense of such sophisticated pagers. Physicians and their healthcare teams can receive immediate feedback regarding side effects. For people who do not respond to a page, a person-to-person telephone call can be made to determine specific problems. People with side effects can be called to determine if strategies can be instituted to alleviate them or if a change in therapy is necessary. Specific information about adherence and adverse effects can be measured more accurately, since recalling specific details days, weeks, or months later can be difficult. When the bill for anti-HIV therapy is $12,000-$15,000 annually, the additional cost of a sophisticated $150 pager plus airtime seems trivial. The authors indicate that a larger trial with the devices will be necessary to confirm the preliminary findings.

Grohskopf, L.A. and others. Feasibility of a two-way electronic pager to enhance adherence with highly active antiretroviral therapy (HAART). 36th IDSA. Abstract 489Sa.

DT 19990110
DOCN BE990114