mental health AIDS

Spring 2006 Newsletter / Volume 7, Issue 3

HIV Treatment News

Medical Care

The National Institute of Allergy and Infectious Diseases (NIAID) halted enrollment in a major international HIV/AIDS trial comparing continuous antiretroviral therapy with episodic drug treatment guided by levels of CD4+ cells. 1 This trial, termed Strategies for Management of Anti-Retroviral Therapy (SMART), involved 318 clinical sites located in 33 countries. At the time enrollment was stopped, 5,472 participants had entered the study.

The analysis revealed that participants on CD4+ cell-guided episodic treatment faced more than twice the risk of disease progression [i.e., the development of clinical AIDS or death] relative to participants on continuous [antiretroviral therapy]. Furthermore, there was an increase in major complications such as cardiovascular, kidney and liver diseases in … participants on the drug conservation arm. These complications have been associated with [antiretroviral therapy], and it was hoped that they would be seen less frequently in those patients receiving less drug. (NIAID, 2006)

Although the risk-to-benefit ratio of an episodic drug treatment strategy over the longer term remains unclear, local study investigators were advised to reinitiate continuous antiretroviral therapy with participants in the drug conservation arm of the study.

As described in the Winter 2006 issue of mental health AIDS, Clifford et al. (2005) conducted a 24-week randomized, controlled study to better characterize the severity and longevity of side effects associated with the use of efavirenz (EFV or Sustiva®). The investigators found that recipients of EFV were more likely to discontinue their prescribed regimen because of neurological or psychological complications than were those who did not receive EFV. Additionally, recipients of EFV reported more sleep disturbances and "bad dreams" during their first week on an EFV-based regimen than did those not receiving EFV. Importantly, no significant differences in depression, anxiety, sleep disturbance, cognitive performance, or neurological symptoms were found between these two groups at weeks 4, 12, and 24.

Others (e.g., Dawson & Woods, 2005) have, however, identified late-onset neuropsychiatric complications in individuals taking EFV. In an effort to predict long-term central nervous system (CNS) toxicity and related neuropsychiatric adverse events associated with the use of EFV, Spanish investigators (Gutiérrez et al., 2005) monitored 17 individuals taking an EFV-containing regimen for a minimum of 6 months at baseline over a subsequent 18-month study period. In this longer timeframe,

[p]atients experiencing neuropsychiatric symptoms during [EFV] therapy usually had drug plasma concentrations > 2.74 μg/mL. This cutoff point was found to have the best discriminatory power to evaluate the risk of CNS toxicity ... . Indeed, patients who had [EFV] plasma concentrations above this value at any time point during the study were much more likely than others to report neuropsychiatric symptoms. Conversely, patients with [EFV] concentrations below this value seem to have a low risk for developing CNS-related adverse events during long-term [EFV] therapy. (p. 1652)

Gutiérrez and colleagues conclude that their findings "confirm that CNS toxicity associated with long-term therapy with [EFV] is related to [EFV] plasma levels, and ... suggest that patients who achieve higher plasma levels may be at increased risk of developing long-term delayed neuropsychiatric adverse events" (p. 1652).

Finally, Purkayastha, Wasi, and Shuter (2005) conducted a study to identify factors associated with sustained virologic suppression among persons receiving care in an urban HIV clinic. The investigators compared characteristics of 64 "case" patients, who demonstrated sustained virologic suppression through at least three viral load measurements taken during 2002, with the characteristics of 64 "control" patients, who did not demonstrate sustained suppression. The investigators found that those "receiving regular follow-up and ... [highly active antiretroviral therapy (HAART)] throughout 2002, on average, demonstrated reasonably good immunologic and virologic parameters regardless of case or control status. Patients with sustained virologic suppression had significantly higher CD4 + lymphocytes at the end of 2002 than patients without sustained ... suppression. Being a nonsmoker, having a risk behavior for HIV acquisition other than heterosexual contact or IDU, and being seropositive for hepatitis C were associated with sustained virologic suppression" (p. 792) in this urban clinic sample.

Indicates this file is in Adobe PDF format and requires the Adobe Acrobat Reader program.

Disclaimer Privacy Policy Accessibility Department of Health and Human Services