In a brief July editorial, "Freedom of Choice," UK-based AIDS Treatment Update
editor Edwin Bernard captures the essence of the present day therapeutic conundrum. "It's ironic," he writes, "that whilst the main focus of this summer's XV International AIDS Conference in Bangkok was on finding ways to get everyone who needs therapy onto HAART, treatment interruption has become a hot topic in well-resourced countries, as concerns over resistance and side effects are increasingly recognised as issues in managing HIV disease."
Whereas at last summer's IAS conference in Paris, two key week on, week off (WOWO) intermittent treatment studies (the Dutch Staccato study and the NIH's own WOWO trial) led to disappointment, this year there has been renewed interest in the concept of pulsed therapy driven by CD4 cell count measures (cycling on and off ART according to pre-defined CD4 count thresholds), due in part to promising preliminary results from the Italian BASTA trial and publicity surrounding the ongoing SMART trial, which is currently enrolling study volunteers in 22 countries worldwide. There was even an admittedly symbolic renaissance of exploration into induction/maintenance approaches.
The BASTA study has patients go off therapy at a CD4 cell count of 800 and then back on at a threshold of 400. The stop/re-start threshold for SMART (www.smart-trial.org) are lower: off treatment once the CD4 cell count rises above 350; re-start if it falls below 250. Edwin's excellent overview of these two key studies can be found at aidsmap.com (www.aidsmap.com/en/docs/1233FABB-86F6-4AF4-955E-4EB5F149F882.asp).
New or updated results from CD4-guided pulse therapy studies (and one intermittent treatment protocol) presented at Bangkok include:
- Ananworanich J, Siangphoe U, Cardiello P, et al. A randomized trial of continuous, CD4-guided and one week on -- one week off HAART in 74 patients with chronic HIV infection: week 108 results. Abstract WeOrB1283.
- Cohen CJ, Morris A, Bazner S, et al. The FOTO Study: A pilot study of short-cycle treatment interruption, taking antiretroviral medications for Five days On, Two days Off (FOTO), for those with viral load suppression. Abstract TuPeB4575.
- Mussini C, Cozzi-Lepri A, Borghi V, et al. A multicentre study on CD4 count-guided treatment interruptions. Abstract TuPeB4569.
- Ruiz L, Gomez G, Domingo P, et al. A multicenter randomized controlled clinical trial of continuous vs. intermittent HAART guided by CD4+ T cell counts and plasma HIV RNA levels: two-year follow-up. Abstract TuPeB4567.
Intriguing results from studies exploring a second therapy-sparing treatment approach, "induction/maintenance," include:
- Arribas JR, Pulido F, Lorenzo A, et al. Simplification to lopinavir/r single-drug HAART: 24 weeks results of a randomized, controlled, open label, pilot clinical trial (OK Study). Abstract TuPeB4486.
- Girard PM, Cabie A, Michelet C, et al. EFV/TDF vs EFV/3TC/TDF as maintenance regimen in virologically controlled patients under HAART: a 6-month analysis of the COOL Trial. Abstract TuPeB4493.
- Markowitz M, Hill-Zabala C, Lang J, et al. Maintenance with Trizivir (TZV) or TZV + efavirenz (EFV) for 48 weeks following a 48-week induction with TZV + EFV in antiretroviral-naive HIV-1 infected subjects. Abstract LbOrB14.
- Ruane P, Luber A, Gaultier C, et al. Maintenance therapy using lopinavir/ritonavir (LPV/r) alone with well-controlled HIV Infection. Abstract TuPeB4577.
- van Raalte R, Heere B, Regez R, et al. Induction-maintenance strategy re-evaluated: initial boosted-PI in combination with triple NRTI, followed by triple NRTI maintenance. Abstract TuPeB4597.