New guidelines on how to manage HIV metabolic complications

The International AIDS Society – USA has published comprehensive recommendations for assessing, monitoring and treating metabolic complications such as insulin resistance and abnormal body fat distribution that are occurring in association with HIV infection and antiretroviral therapy.

The recommendations, published in the November 4 issue of the Journal of Acquired Immune Deficiency Syndromes, identify five major areas of concern: insulin resistance with alterations in glucose metabolism, abnormalities in lipid metabolism, lactic acid disorders, bone disease, and abnormal body fat distribution.

In the article, the IAS-USA panel makes recommendations to clinicians regarding tests to identify and monitor metabolic complications in HIV-infected patients on antiretroviral therapy in each of the five areas. Approaches such as switching antiretroviral therapy, treatment of the complication with medication and behaviour change such as diet and exercise are evaluated and recommended for each complication.

To develop the recommendations, IAS-USA selected a twelve-member international panel of experts in HIV clinical care, antiretroviral therapy, and endocrine and metabolic disorders in 2000. The panel reviewed results of clinical, epidemiological, and basic science studies and data, including studies of similar abnormalities in non-HIV infected persons. For each metabolic complication, the panel reviewed all available evidence. The recommendations of the panel were determined by full group consensus.

In its 2001 Adult Antiretroviral treatment guidelines (pages 24-29), the British HIV Association made a range of recommendations regarding management of metabolic changes in HIV-positive individuals. Places where the IAS-USA guidelines differ from the BHIVA guidelines, or make recommendations on topics that are not covered in the BHIVA guidelines, are highlighted below.

Consensus recommendations on monitoring and intervention that differ from the 2001 BHIVA guidelines:

Insulin resistance

Measure fasting glucose before and during treatment (3-6 months after starting and at least annually thereafter).

Cholesterol

Fasting total, LDL and HDL cholesterol should be obtained prior to starting therapy, after 3-6 months on treatment and at least annually thereafter.

Recommend the use of total cholesterol: HDL cholesterol ratios where LDL cholesterol values cannot be obtained due to hypertriglyceridemia (>4.5mmol/L).

Framingham tables should be used to establish risk and individualise interventions. In addition the NCEP treatment recommendations, based on LDL cholesterol, should be used for considering when to intervene and to define the LDL and non-HDL cholesterol goals of intervention.

Triglycerides

Fasting triglycerides should be measured prior to starting treatment, 3-6 months after starting treatment, and at least annually thereafter.

Intervention threshold: > 5.6mmol/L (BHIVA recommendation 8mmol/L)

Where therapy for elevated triglycerides and LDL cholesterol is indicated, it is recommended that statin treatment should begin first, and fibrate treatment should only be added after four months if the response is sub-optimal, due to the risk of rhabdomyolysis.

Dietary intervention

Follow National Cholesterol Education Program dietary guidelines.

Body fat changes

Aerobic and resistance exercise should be encouraged for individuals with central or generalized fat accumulation, both for its potential to reduce central fat and its moderating effect on hypertriglyceridemia.

Dietary interventions should focus on reducing saturated fat, simple carbohydrate and alcohol intake.

Growth hormone cannot be recommended for routine use because the optimal dose and risk:benefit ratio have not been identified.

Testosterone and rosiglitazone cannot be recommended due to lack of evidence, but metformin may be effective in patients with central fat accumulation and glucose intolerance or insulin resistance, and may be a preferred modality when treatment of the latter is necessary.

Lactic acidemia

BHIVA guidelines define lactic acidosis as venous lactate > 5mmol/L and arterial pH less than or equal to 7.35.

IAS-USA guidelines define lactic acidosis as venous lactate >2mmol/L and arterial pH less than 7.3.

IAS-USA recommend that antiretroviral therapy should be discontinued in all patients with plasma lactate levels of 10mmol/L or above, and in those with symptomatic hyperlactatemia and plasma lactate levels above 5mmol/L. Therapy may be reintroduced after lactate levels normalize, but alternative nucleoside analogues should be included with caution, and lactate levels should be monitored every four weeks for at least three months.

BHIVA guidelines recommend that antiretrovirals should be stopped in all individuals with lactic acidosis, and supportive measures such as ensuring adequate perfusion and providing supportive oxygen should also be considered. BHIVA guidelines also strongly recommend that all clinicians and all patients must be familiarised with the symptoms of lactic acidosis and hyperlactatemia.

Bone disease

Routine screening for osteoporosis is not recommended, but X-ray of the femoral head or other bone where pain is present should be carried out. The contralateral joint should also be scanned because bilateral disease is common. Joint replacement and surgical resection of the affected bone is the only effective treatment. Assessment of risk factors for osteoporosis should be carried out if reduced bone mineral density is found, and dietary calcium and vitamin D intake should be assessed. If a fracture occurs, therapy with a biophosphonate should be considered.

Panel members

Chair: Morris Schambelan, Professor of Medicine,UCSF & Director of the General Clinical Research Center at San Francisco General Hospital Medical Center;

Co-chair: Constance A. Benson, MD, professor of medicine, Division of Infectious Diseases, the University of Colorado Health Sciences Center;

Andrew Carr, MD, associate professor of medicine, HIV, Immunology, and Infectious Diseases Clinical Service Unit, St. Vincent's Hospital, Sydney, Australia;

Judith S. Currier, MD, UCLA associate professor of medicine, associate chief, Division of Infectious Diseases, UCLA Medical Center;

Michael P. Dube, MD, associate professor of medicine, Indiana University School of Medicine; John G. Gerber, MD, professor of medicine and pharmacology, University of Colorado Health Sciences Center;

Steven K. Grinspoon, MD, associate professor of medicine, Harvard Medical School;

Carl Grunfeld, MD, PhD, UCSF professor of medicine, chief of the metabolism and endocrine sections at the San Francisco Veterans Affairs Medical Center;

Donald P. Kotler, MD, professor of medicine, St. Luke's-Roosevelt Hospital, Columbia University;

Kathleen Mulligan, PhD, UCSF associate professor of medicine at San Francisco General Hospital Medical Center;

William G. Powderly, MD, FRCPI, professor of medicine, chief, Division of Infectious Diseases, Washington University School of Medicine;

Michael S. Saag, MD, professor of medicine, The University of Alabama at Birmingham.