New HIV guidelines offer adverse effects data
New guidelines available on-line or in booklet
The "Guidelines for Using Antiretroviral Agents Among HIV-Infected Adults and Adolescents" have been updated with additional information linking the use of antiretroviral therapy to chronic diseases and adverse events. The guidelines, which are recommendations of the Panel on Clinical Practices for Treatment of HIV, were prepared by the National Center for HIV, STD, and TB Prevention and the Division of HIV/AIDS Prevention - Surveillance and Epidemiology, Centers for Disease Control and Prevention of Atlanta. Representatives from the National Institutes of Health in Bethesda, MD, and Johns Hopkins University in Baltimore also were involved in updating the guidelines.
Here are some of the new aspects of the updated guidelines:
• New studies offer additional information about when clinicians should initiate antiretroviral therapy among asymptomatic patients. One such collaborative analysis of data from 13 cohort studies conducted in North America and Europe showed that there is a 15.8% 3-year probability of progression to AIDS or death among drug-naive patients who do not have AIDS-defining illness, whose viral load is less than 100,000 copies/mL, and for whom therapy was initiated when their CD4+ T-cell counts were 0-49 cells/mm3. This rate dropped to 9.3% for those whose CD4+ T-cell counts were 100-199, to 4.7% among those whose CD4+ T-cell counts were 200-349, and to 3.4% among those with CD4+ T-cell counts of 350 or higher. (See table.)
| Risks and Benefits of Delayed vs. Early Therapy Initiation for the Asymptomatic HIV-infected Patient | |
| Benefits of delayed therapy initiation | |
| • | Avoid negative effects on quality of life (i.e., inconvenience) |
| • | Avoid drug-related adverse events |
| • | Delay in experiencing drug resistance |
| • | Preserve maximum number of available and future drug options when HIV disease risk is highest |
| Risks of delayed therapy initiation | |
| • | Possible risk for irreversible immune system depletion |
| • | Possible increased difficulty in suppressing viral replication |
| • | Possible increased risk for HIV transmission |
| Benefits of early therapy initiation | |
| • | Control of viral replication easier to achieve and maintain |
| • | Delay or prevention of immune system compromise |
| • | Lower risk for resistance with complete viral suppression |
| • | Possible decreased risk for HIV transmission* |
| Risks of early therapy initiation | |
| • | Drug-related reduction in quality of life |
| • | Greater cumulative drug-related adverse events |
| • | Earlier development of drug resistance, if viral suppression is suboptimal |
| • | Limitation of future antiretroviral treatment options |
| *The risk for viral transmission still exists; antiretroviral therapy cannot substitute for primary HIV prevention measures (e.g., use of condoms and safer sex practices). | |
| Source: "Guidelines for Using Antiretroviral Agents Among HIV-Infected Adults and Adolescents," updated 2002. | |
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• A protease inhibitor (PI)-sparing regimen of abacavir plus two nucleoside reverse transcriptase inhibitors (NRTIs) has been shown to produce a similar viral load suppression and CD4+ T-cell response as PI-containing regimens and the other PI-sparing regimen of efavirenz plus two NRTIs. The guidelines caution that whether these PI-sparing regimens will provide comparable efficacy with regard to clinical outcomes still is unknown.
• Evidence continues to mount that NRTIs can lead to chronic compensated hyperlactatemia. Also, severe lactic acidosis with or without pancreatitis have been reported during the later stages of pregnancy or among postpartum women who were on an antiretroviral therapy of stavudine and didanosine plus other agents during the later stages of pregnancy. There were three reported deaths from this adverse effect.
• The guidelines carry further information about the connections between HIV treatment and hepatitis. Among the non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine has the greatest potential for causing clinical hepatitis. Reports show a 12.5% incidence of hepatotoxicity among patients initiating nevirapine, with clinical hepatitis diagnosed for 1.1% of these patients. Clinicians may watch for signs of unexplained onset and persistence of abdominal distention, nausea, abdominal pain, vomiting, diarrhea, anorexia, dyspnea, generalized weakness, ascending neuromuscular weakness, myalgias, paresthesias, weight loss, and hepatomegaly.
• The guidelines also discuss the potential for hyperglycemia resulting from peripheral and hepatic insulin resistance, relative insulin deficiency, an impaired ability of the liver to extract insulin, and a longer exposure to antiretroviral medications. Reports have put the incidence of hyperglycemia with or without diabetes at 3% to 17% of patients in multiple retrospective studies. The reports found that the symptoms of hyperglycemia were reported at a median of 60 days after initiation of PI therapy. Some of those who discontinued therapy found that their hyperglycemia was resolved, and other patients continued with PI therapy and began treatment with oral hypoglycemic agents or insulin. According to the guidelines, "Clinicians are advised to monitor closely their HIV-infected patients with pre-existing diabetes when PIs are prescribed and to be aware of the risk for drug-related, new-onset diabetes among patients without a history of diabetes."
Warning signs should be monitored, such as polydipsia, polyphagia, and polyuria. The guidelines say some clinicians recommend routine fasting blood glucose measurements at quarterly intervals during the first year of PI therapy for those without a previous history of diabetes, and there should be closer monitoring of pregnant women receiving PI-containing regimens. Lacking data, the guidelines make no recommendations on whether a clinician should continue or discontinue drug therapy among patients with new-onset or worsening diabetes. However, the guidelines note that most experienced clinicians recommend continuation of antiretroviral therapy in the absence of severe diabetes.
• Evidence from recent research suggests that dyslipidemias, which have been associated primarily with PIs, may be a drug-specific rather than class-specific toxicity. The guidelines say dyslipidemia frequently is severe enough to consider therapeutic interventions, and it’s possible that lipid elevations may be associated with accelerated atherosclerosis and cardiovascular complications among HIV-infected patients.
• The NNRTI class of drugs is the class most commonly associated with skin rashes within the first weeks of therapy. These tend to be mild to moderate, and some clinicians recommend managing the rash with antihistamine for symptomatic relief without drug discontinuation. Recent research shows that female patients may have a seven-fold higher risk for developing grade 3 or 4 skin rashes than male patients. Based on recent data, the guidelines do not recommend using systemic corticosteroid or antihistamine therapy at the time of the initiation of nevirapine to prevent the skin rash, because this has not proven effective and may even result in a higher incidence of skin rash.
To obtain the entire guidelines, references, and tables, contact the HIV/AIDS Treatment Information Service (ATIS). Telephone: (800) 448-0440. Fax: (301) 519-6616. Web site: www.hivatis. org. The information also is available at these web sites: www.cdcnpin.org, http://hiv-web.lanl.gov, or www.cdc.gov/mmwr/preview/mmwrhtml/rr5107a1.htm.
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