Life Without NRTIs: A Simpler, More Effective Treatment Plan for HIV/AIDS Patients

By Karen Tolentino | UTS Staff Writer | SQ Online (2014-15)


Since the first outbreak of the HIV/AIDS epidemic in the early 1980s, the Antiviral Research Center (AVRC) at UC San Diego has been at the forefront of HIV/AIDS research, establishing the first longitudinal study of the complications of AIDS in 1984. Today, their work continues at the Owen Clinic, the AVRC’s outpatient treatment center for patients with HIV/AIDS, as well as in their clinical trials and research studies. The AVRC has been integral in a new study that seeks to prove that patients can discard an entire class of antiretroviral drugs from their daily regimens, which often consist of several different classes of medication. Before delving into specifics, it is necessary to provide some background on antiretroviral medication and the HIV virus.

The rapid rate at which HIV undergoes mutations and its high degree of variability make it difficult to develop a permanent cure. At best, the virus can be suppressed to nearly undetectable levels. HIV itself was first identified as a retrovirus in 1984, and the first drug to succeed in limiting HIV replication, azidothymidine, was developed in 1985. Azidothymidine, or AZT, is a type of drug called a nucleoside reverse transcriptase inhibitor (NRTI); it replaces a component of DNA called deoxythymidine, effectively preventing the HIV virus from using reverse transcriptase to integrate itself into nuclear DNA.

In the beginning of the HIV/AIDS epidemic, AZT was an effective therapy for many patients. However, because of the virus’s adaptive capabilities and poor regimen adherence, some strains of AZT-resistant HIV evolved. Patients who were solely prescribed AZT experienced a relapse in symptoms after some time spent taking the drug. Strains of HIV resistant to the NRTI class became more prevalent amongst the population. The limited effectiveness of AZT and of other NRTIs led to the development of several new classes of antiretroviral medications (ARVs), such as protease inhibitors and non-NRTIs. Consequently, many HIV patients today are put on a cycle of various ARVs to stop the development of another resistant strain, as research has shown that the HIV virus has trouble adapting when simultaneously bombarded by a number of therapeutic agents. This course of intensive treatment is known as Antiretroviral Therapy, or the ART program.

At the Owen Clinic, it is not unusual to see patients on regimens requiring that they take upwards of 20 to 30 pills a day. The large number of pills often leads to poor adherence to the regimen and, consequently, resistance to ART medications. A longer period of participation in the ART program leads to a higher likelihood that a patient will develop resistance to antiretroviral medication. Missing even one day of medication could allow the virus to adapt, negating the effects of further treatment. Regimen adherence is critical – a point that is repeatedly stressed during visits to the Owen Clinic.

Recently, the AVRC participated in a multi-center study with the Miriam Hospital in Providence, Rhode Island. The OPTIONS study was successful in proving that HIV/AIDS patients who have developed a resistance to the NRTI class of antiretroviral drugs could eliminate NRTIs from their regimens. Karen Tashima, MD, of Miriam Hospital served as study chair while Richard Haubrich, MD, of the AVRC served as co-chair. A total of 413 patients were part of the study, within the parameters that they were at least 16 years of age and showed some resistance to HIV medications. To ensure that they maintained viral suppression throughout the course of the study, a web utility was used to carefully review patient records and create a treatment plan. Half of the patients’ treatment plans included NRTIs, while the other half did not. The patients were part of the study for 96 weeks. Over the course of the study, patients’ viral loads – the amount of HIV virus in the bloodstream – were carefully monitored to ensure that they maintained the same levels of viral suppression. Overall, it was found that patients who took NRTIs and those who did not had similar viral loads at the end of the study.

The results show that NRTIs can be eliminated from treatment plans completely, reducing the number of pills that patients are required to take as part of the ART program. It is hoped that this breakthrough will promote regimen adherence while continuing to subdue HIV replication, prevent resistance to therapeutic agents and lower the cost of medication. The outcome could significantly change traditional approaches to HIV treatment.

The OPTIONS study has provided some insight into preventing viral replication and has raised curiosity regarding further immunologic research. According to Karen Tashima, “There is no question that the results show what we had set out to prove – a treatment-experienced patient will not lose virologic suppression by omitting NRTIs. We are so excited to show this data.”

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  • Fan, Hung, Ross F. Conner and Luis P. Villarreal. AIDS: Science and Society. Sudbury, MA: Jones and Bartlett, 2007. Print.
  • “HIV Therapy Just Got Easier: Fewer Drugs May Be Needed for Treatment-Experienced Patients.” AVRC. UC San Diego School of Medicine, n.d. Web. 06 Aug. 2014.