BIOL 2404 A&P Basics                      Case Study: Immune                Dr. Weis

Academic Medical Center                           Drug Therapy Study Report

Background:

Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long term use of multi drug regimens is difficult to sustain due to the high costs of the drug, number of medications, and overall lifestyle impact.  Simplifying antiretroviral treatment regimens would increase patients’ adherence and minimize toxicity.  This study investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART.

Study Summary:

Patient selection was based on a positive test for HIV-1 with at least 1000 HIV-1 RNA copies/ml in plasma, a 200 CD4 cells/μl, and no previous exposure to antiretroviral drugs.

Results:

Induction therapy for all patients included stavudine, lamivudine, saquinavir, and nelfinavir.  Patients were then randomly allocated maintenance therapy of two of these drugs or else placed on prolonged induction therapy using all four drugs.

At the conclusion of the study, those patients on prolonged induction therapy had a negative or lower detectible HIV-1 RNA than those patients on maintenance therapy. 

In addition, the initial viron-clearance rate was higher with prolonged induction therapy and continued to sustain undetectable plasma HIV-1 RNA concentration after 36 weeks.

Conclusion:

The induction regimen provided a rapid suppression of viral replication to below 50 copies/ml.  However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy.  It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.

Treatment failures exist for reasons that include patient noncompliance, drug pharmacokinetics, and resistance to one or more drugs in the treatment regimen due to viruses acquiring drug resistance mutations.  New genotypic* and phenotypic^ tests for identifying drug resistant strains of HIV can help clinicians determine the cause of drug failure and select alternative regimens for their patients with HIV.

Notes:

* Genotypic tests are designed to flag specific mutations in HIV’s genetic makeup that have been linked to drug resistance.

^ Phenotypic tests measure how well a patient’s strain of HIV will grow in the presence of anti-HIV drugs.