Reports for NATAP

1st International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment

July 7-11, 2001 Buenos Aires, Argentina

STI vs. Continuous HAART during Chronic HIV Infection
     Written for NATAP by Michael Norton, PA

Abstract #56 – Franco Lori and colleagues – RIGHT Study 901

Entry Criteria
         - Antiretroviral Naïve
         - Chronically infected
         - CD4+ T-cells > 250 cells/mm3
         - VL > 5,000 copies/ml

Baseline Characteristics
        - N = 60
        - Gender given as "mostly Men"
        - Median VL = not given
        - Median CD4+ T-cell = not given

Design
        - Prospective study
        - Primary Objective: Safety and tolerability of scheduled STI
        - Secondary Objective: Compare STI results with HU containing regiment to traditional HAART of 2 nucs and PI.
        - 2 arms randomized to:
                o IDV, D4T, DDI
                o DDI, D4T, HU
        - Both arms started with 12 weeks of continuous therapy
        - After 12 weeks further randomization to:
                o 3 weeks on, 3 weeks off therapy x 4 cycles
                o continuous HAART
        - All patients stop therapy at 36 weeks

Results
        - Interim analysis @ 36 weeks of the first 30 patients to reach this time point
        - Looking at the continuous therapy group:
                o While on therapy, IDV group showed greater increases in cd4+ T-cells when compared to the HU group.
        - Looking at the STI group:
                o Each time both arms (HU & IDV) interrupted therapy viremia came back to baseline.
                o With each interruption, the time it took to reach baseline VL did not increase or lengthen, but remained the same.
                o Re-suppression after interruptions was achievable.
o HU STI group showed greater and steadier increase in CD4+ T-cells when compared to IDV STI group.
        - After discontinuing therapy after 36 weeks, all 4 arms went back to baseline viral load, and there was no difference in CD4+ T-cells.

Discussion
    During the Q & A, Lori stated that he would not recommend D4T with HU however he still recommends DDI with HU, especially in resource poor settings where this combination is less expensive. In response to another question, he stated that at this time there was no resistance data available from this study at this time.

Commentary
    This study as well as its interim analysis raises a number of questions about the current state of much of the presentations at the so-called scientific HIV/AIDS conferences. While being powered to answer the question of safety and tolerability or some other easy parameter, what is presented and focused on is efficacy and equivalency. To truly answer those questions takes much larger trials. Also the endless rush to have something at every conference to present, has led pharmaceutical companies and researchers alike to present data on an interim basis. These interim analyses often bias both the researchers as well as the audience.

     Looking particularly at this study, I could not tell you from what was presented, how many patients were in each arm for the comparison at 36 weeks. I am assuming, perhaps erroneously, that because this is a safety and tolerability study that the randomization was sequential,(one to IDV arm then one to HU arm, then after 12 weeks one to STI arm one to continual therapy arm), which would make the arms about even at 36 weeks. Separately, because the oral presentation, slides, and discussion focused on equivalency, I would at least like to know the median VL and T-cell of each arm at baseline.

     The flaws not withstanding, this study does make two points worth considering. While small, this is yet another observation of chronically infected, well suppressed patients, over a 1 year period of time, taking structured therapeutic interruptions without obvious identifiable risks. It also suggests that HU deserves further investigation as an agent if STI’s are to be employed.

(Editorial note: other studies have shown risks associated with STIs (cd4 decreases, viral load increases, opportunistic infections). As well, a number of studies show potential toxicity associated with hydroxyurea particularly in very treatment experienced patients. Certainly, if HU is used, close monitoring for toxicity and side effects should be performed).