Abstracts 316 and 372

• Abstract 316: Switching Off Protease Inhibitors: An Observational Study of Well Controlled HIV Patients Who Opted to Change to Efavirenz and/or Abacavir Based Regimens After Initial Treatment with Protease Inhibitors
  Authored by Malte R. Schutz and Scott McCallister
  
  
  
• Abstract 372: Long Term Efficacy of Protease Inhibitor (PI) Induced HIV-1 Suppression Followed by Switch to Non-PI Maintenance Antiretroviral Therapy
  Authored by William C. Woodward, Judy Lash, and Robert Eric Doerfler

The HIV protease inhibitors revolutionized antiretroviral therapy -- following their introduction and their use as part of three-drug combinations, the frequency of opportunistic infections and the death rate due to complications of AIDS declined dramatically. However, as a class, the currently available protease inhibitors may be difficult drugs for patients to take long-term. Taking protease inhibitors often means swallowing a relatively large numbers of pills, coordinating the pill taking with meals or times of the day when the stomach is empty, a high incidence of gastrointestinal side effects, and experiencing changes in body shape resulting from a redistribution of body fat. In addition, there is the growing concern that the elevated triglyceride and cholesterol levels, and the abnormal glucose and insulin metabolism that is associated with these drugs may place patients at an increased risk of developing cardiac disease and diabetes. Therefore, several studies are underway to determine whether viral loads stay suppressed in patients switching off protease inhibitors, and whether the changes in body fat and elevated lipid levels are reversible.

Two posters are reported here, describing the experiences of a total of 55 patients who switched therapy from a protease inhibitor inclusive combination to one including a non-nucleoside reverse transcriptase inhibitor or abacavir.

In an open-label, observational study, Malte Schutz and Scott McCallister switched the antiretroviral combinations of 34 patients who had a viral load < 400 copies/mL. Twenty-three of 25 patients who had an ultrasensitive viral load at the time of treatment switch had a viral load < 50 copies/mL. The mean CD4+ count at the time of switch was 440 (range 151 - 1223 cells/mm3). Approximately half of the patients had a previous antiretroviral combination before beginning the protease inhibitor inclusive combination that had brought their viral load down below quantifiable levels. Patients continued on their two nucleoside reverse transcriptase inhibitors and switched their protease inhibitor (mostly indinavir, nelfinavir, or ritonavir + saquinavir) to efavirenz, efavirenz plus abacavir, or abacavir) All 18 patients whose treatment was switched to efavirenz had a viral load < 50 copies/mL after a mean follow-up period of 29 weeks (range: 8 - 63 weeks). Seven of 8 patients who switched to efavirenz plus abacavir had a viral load < 50 copies/mL after a mean follow-up of 38 weeks (range: 20 - 50 weeks). The one patient with a quantifiable viral load had a viral load of 136 copies/mL after 36 weeks. In contrast, only 4 of 8 patients who were switched to abacavir maintained a viral load < 50 copies after a mean follow-up of 25 weeks (range: 8 - 39 weeks). Two of the patients with a quantifiable viral load had a viral load of 50 - 200 copies/mL, the other two had viral loads of 1,700 - 5,700 copies/mL.

In another open-label observational study, Chris Woodward and colleagues described 21 of their patients who switched from a combination with one or two protease inhibitors to a combination with nevirapine (20 patients) or efavirenz (1 patient). Approximately half of the patients switched the reverse transcriptase inhibitor component of therapy to ddI + 3TC, both given once daily. Patients taking ddI + 3TC also took nevirapine (or efavirenz) once daily. The other patients who continued their reverse transcriptase inhibitors took nevirapine twice daily. Eight of the patients had were antiretroviral naïve before starting their PI-containing combination. The viral load was < 50 copies/mL for 1 month - > 12 months prior to the switch. Two patients who switched to nevirapine experienced a viral load rebound. One patient on nevirapine died of liver disease and another patient taking nevirapine, ZDV, 3TC, ddI, and hydroxyurea was reported to have "died suddenly."

What do these studies tell us? It seems that in the majority of cases a patient can switch off a protease inhibitor onto another combination and maintain suppression of viral replication sufficient to keep their viral load < 50 copies/mL. Whether patients will have equal success after switching to efavirenz, nevirapine, or abacavir remains to be seen. The patient's previous antiretroviral experience, their viral load at the time of switch (I don't think a patient should ever be switched unless their viral load is documented at < 50 copies/mL prior to switching), the length of time their viral load is below quantifiable levels, and their CD4+ count may all be variables that predict a successful outcome. Further, controlled studies in which patients switch or continue are needed to determine what patients can safely switch therapy. Neither of these two studies reported on fat redistribution or lipid or glucose abnormalities. Whether these complications will be seen less frequently in patients treated with a non-nucleoside based antiretroviral combination, as opposed to a protease inhibitor, is not known. Patients who are tolerating their PI-containing combination well and who are not experiencing fat redistribution or changes in lipid or glucose levels are probably better off remaining on their current combination.