Clinical Context
The European AIDS Clinical Society (EACS), a nonprofit group of European physicians, clinicians, and researchers, has reviewed the clinical management of HIV. The statement describes EACS recommendations for initial assessment, antiretroviral therapy treatment, prevention and management of noninfectious comorbidities, and management and treatment of chronic hepatitis B and C coinfections in patients who are HIV-positive.
Study Synopsis and Perspective
The latest guidelines of the EACS, released here at the society's 13th European AIDS Conference, give special emphasis to comorbid conditions that may occur in patients infected with HIV.
"The contemporary challenge in HIV medicine is no longer to suppress the virus but actually to maintain health of patients with HIV, and the major focus now and the dominating reason for why people are still getting sick, even for those who are in care, is the development of various co-morbidities," said Jens Lundgren, MD, DMSc, professor in the Department of International Health, Immunology and Microbiology at the University of Copenhagen, Denmark, director of the Copenhagen HIV Program in Denmark, and chairman of the section on comorbidities of the guidelines committee.
Fortunately, suppression of HIV has become so effective that comorbid conditions are a real concern. "HIV physicians are great in treating the virus but may not have the skill set necessarily to deal with the prevention and treatment of the co-morbidities," he noted. "We have involved experts in the fields of the organ diseases, and therefore we believe that we are providing contemporary guidance on that."
This focus on comorbid conditions constitutes a major revision to the previous set of guidelines, issued in 2009. The most recent set, version 6, is available at www.europeanaidsclinicalsociety.org in English and several other languages. Guidelines have been issued every 2 years at the biennial EACS conference.
Organization of Guidelines
The goal of the design of the guidelines was to make them easy to use in routine clinical practice yet comprehensive enough to address the patient as a whole. The guidelines are organized in 4 sections:
- Assessment of HIV-infected patients at initial and subsequent visits;
- Antiretroviral treatment of HIV-infected patients;
- Prevention and management of noninfectious comorbid conditions with HIV; and
- Clinical management and treatment of chronic hepatitis B and C co-infection in HIV-infected adults.
Dr. Lundgren advised that clinicians cannot use the same approach in treating comorbid conditions with HIV as they do in the general population since HIV affects the risk for diseases in various organs. "Equally, the medicines that you use to prevent and treat these comorbidities interact with the drugs that we are using to treat the HIV virus itself," he said at a news conference that Medscape Medical News attended. "Therefore, it's quite important that when you care for people with HIV that you have a comprehensive look at the person rather than just focusing on the virus itself."
Beginning on page 10 of the printed English version is a 6-page chart delineating a standard of care for the assessment of HIV-infected patients at initial and subsequent visits through interviews and laboratory tests. It deals with history (including medical, psychosocial, and sexual and reproductive health), HIV disease, co-infections, and noninfectious comorbid conditions.
A Web version in development (links at www.europeanaidsclinicalsociety.org) will expand on the print versions with additional information, tables, and links to resources on lifestyle interventions, antidepressant drugs, renal tests, drug dosage adjustments for renal impairment, other drugs and dosing with comorbid conditions, drug dependency and addiction, management of metabolic disorders, and activities of daily living.
Specific Features
The guidelines help clinicians assess patients' readiness to initiate treatment with antiretroviral drugs based on behaviors, cognitive problems, level of health literacy, health insurance and access to drugs, and social support and disclosure. Then they make 3 levels of recommendation for initiating therapy according to the CD4 cell count and the presence of various health conditions and comorbid conditions. The recommendations are:
- R: recommended
- C: consider (some level of uncertainty; more evidence from randomized trials is needed)
- D: deferral of therapy
Significant attention is given to adverse effects and drug-drug interactions.
Noninfectious Comorbid Conditions in HIV
Tables or flow charts lead clinicians through cancer screening, including for hepatocellular carcinoma in the presence of cirrhosis; prevention of cardiovascular disease; hypertension diagnosis and management; and treatment of diabetes, depression, bone, and kidney disease.
Dr. Lundgren said all patients should be scored for their risk for cardiovascular disease with an HIV-specific risk equation, and one should consider modifying antiretroviral therapy if the 10-year risk for a cardiovascular event is greater than 20%.
An update from the 2009 guidelines concerns lipid-lowering therapy, which is now recommended only if the 10-year risk is greater than 20% in primary prevention.
Another modification from the 2009 version concerns blood pressure. "For people diagnosed with hypertension with an age of less than 55 [years], the recommended initial medication is an [angiotensin-converting enzyme] inhibitor whereas for people who are above 55 or black patients of any age, the recommended first choice is a calcium-channel blocker," Dr. Lundgren said. If single-agent therapy is not sufficiently effective, a diuretic may be added. "This is a fairly substantial change in recommendations for management of hypertension compared to the 2009 [guidelines], and again, this is done out of the advice of colleagues expert in the hypertension field," he said.
He noted that there has been much discussion of what is the appropriate cut-off for the diagnosis of impaired glucose tolerance, and the guidelines panel agreed on a fasting plasma glucose level of 5.7 to 6.9 mmol/L (110 to 125 mg/dL), as recommended by the World Health Organization and the International Diabetes Federation in 2005.
For first-line treatment, the panel recommends first considering use of metformin or possibly sulfonylureas, depending on specific patient characteristics. HIV-specific factors can affect glycated hemoglobin values, so plasma glucose may be a better indicator of the need for treatment. As good practice would dictate, clinicians are urged to screen their diabetic patients for nephropathy, retinopathy, and polyneuropathy.
Screening for kidney disease is an evolving area, but Dr. Lundgren advised that "it is absolutely clear now that we do need HIV clinics to start to screen the urine for protein in order for you to be able to calculate the urine protein-to-creatinine ratio because this has major impact not only on the progression of the kidney disease but also on extra-renal complications for people with impairment of renal function... so we can no longer just take blood from patients."
It is also important to determine the estimated glomerular filtration rate, and there are various standard methods. A table in the guidelines has been simplified from the previous version for managing individual patients according to estimated glomerular filtration rate and the urinary protein-to-creatinine ratio.
The antiretroviral drugs tenofovir, indinavir, and atazanavir can be nephrotoxic, and a table presents management strategies in this still-evolving area. "The question at the moment is whether there is an immediate hit from using these drugs or whether there is a gradual deterioration of renal function," Dr. Lundgren said.
A section on vaccination lists rationales, dosing, and schedules in the setting of HIV infection, as well as the use of live vs attenuated vaccines, which ones to combine or not, and assessing effectiveness using antibody titers.
Recreation and Enjoyment of Life
The guidelines help clinicians make recommendations to their patients who want to travel. A table provides general precautions, advice on antiretroviral therapy, and the need for extra awareness because of their heightened susceptibility to food and insect-borne diseases. It also refers people to www.hivtravel.org for advice on travel restrictions.
A new section gives clinicians systematic guidance on assessing and treating sexual dysfunction in people living with HIV, including taking a general sexual history, determining the nature of the complaint, identifying the cause of the problem, and making the appropriate referral.
EACS sponsored development of the guidelines and did not receive any industry support. Dr. Lundgren has disclosed no relevant financial relationships. He chaired the comorbidity section on the guidelines committee.
13th European AIDS Conference, Belgrade, Serbia. Guidelines presented at a special session. No abstract. Presented October 14, 2011.
Related Link
AIDSinfo , a service of the U.S. Department of Health and Human Services (HHS), offers a clinical guidelines portal with links to all applicable US HIV/AIDS-related guidelines for adults and adolescents, children, and perinatal patients.
AIDSinfo , a service of the U.S. Department of Health and Human Services (HHS), offers a clinical guidelines portal with links to all applicable US HIV/AIDS-related guidelines for adults and adolescents, children, and perinatal patients.
Study Highlights
- The latest guidelines of the EACS indicate that the initial history of an HIV patient includes medical, psychosocial, and sexual and reproductive health.
- Initial laboratory tests include confirmation of HIV Ab positive test, plasma HIV RNA, genotypic resistance test and subtype, CD4 absolute count and percentage, and R5 tropism and HLA B5701 if available.
- Initial assessment of coinfections includes a sexually transmitted infection screen, syphilis serology, hepatitis A serology, hepatitis B and C screens, chest X-ray and purified protein derivative for tuberculosis, and serology for varicella zoster virus, measles, rubella, toxoplasma, cytomegalovirus, leishmania, and tropic parasites.
- Initial assessment of noninfectious comorbidities includes blood count, hemoglobinopathies, glucose-6-phosphate dehydrogenase, body mass index, Framingham risk assessment score, electrocardiogram, blood pressure, lipid screen, plasma glucose, alanine aminotransferase/aspartate aminotransferase, alkaline phosphatase, bilirubin, estimated glomerular filtration rate, urine dipstick, bone profile, fracture risk assessment if older than 40 years, 25 OH vitamin D, screening for neurocognitive impairment, depression, and cancers.
- Patients should be assessed for readiness to start antiretroviral therapy.
- Antiretroviral therapy initiation in HIV-positive patients without prior antiretroviral therapy exposure is recommended for
- All with a CD4 count lower than 350 cells/µL
- A CD4 count of 350 cells/µL or higher plus symptomatic HIV, pregnancy before third trimester, HIV-associated kidney disease, HIV-associated neurocognitive impairment, Hodgkin's lymphoma, human papillomavirus–associated cancers, or hepatitis B requiring anti–hepatitis B treatment
- A CD4 count of 350 to 500 cells/µL plus hepatitis B not requiring anti–hepatitis B treatment or hepatitis C for which anti–hepatitis C treatment is being considered, given, or not feasible.
- The initial combination regimen for antiretroviral-naive adults is nonnucleoside reverse transcriptase inhibitors plus abacavir/lamivudine or tenofovir/fixed dose combination, ritonavir-boosted protease inhibitors plus abacavir/lamivudine or tenofovir/fixed dose combination, or integrase transfer inhibitors plus tenofovir/fixed dose combination.
- Considerations during pregnancy include frequent monitoring, teratogenic drug effects, gestation, and benefits vs risk for caesarean section delivery.
- In patients with tuberculosis, antiretroviral therapy can interact with antituberculosis therapy; the recommended antiretroviral is efavirenz/tenofovir/fixed dose combination.
- Antiretroviral drugs can have adverse effects that affect all body systems and can interact with cardiovascular, central nervous system, anti-infective, and miscellaneous drugs.
- If cardiovascular disease risk is 20% or higher, then antiretroviral therapy modification can be considered.
- Hypertension treatment depends on grading and possible interactions with antiretroviral therapy.
- Type 2 diabetes treatment with sulfonylureas has not been studied in patients who are HIV-positive.
- Dyslipidemia treatment with statins might be affected by antiretroviral therapy.
- Depression is more prevalent in the HIV-positive populations vs the general population (20% - 40% vs 7%), and screening is recommended.
- Osteopenia, osteoporosis, osteomalacia, and osteonecrosis are more prevalent in patients who are HIV-positive; antiretroviral therapy can be associated with bone mineral density loss and lower vitamin D.
- Renal disease management depends on estimated glomerular filtration rate results, proteinuria, and antiretroviral therapy–associated nephrotoxicity.
- Increased alanine aminotransferase/aspartate aminotransferase results require assessment for hepatoxic medications, alcohol intake, viral hepatitis, and other causes.
- Patients with cirrhosis have greater survival with antiretroviral therapy initiation and should be screened every 6 months with serum alpha-fetoprotein and hepatic ultrasound for hepatocellular carcinoma.
- Lipodystrophy requires modification of antiretroviral therapy.
- Travel precautions include medication documentation, dosage timing, and increased risk for infection.
- Vaccination precautions include possible low response and contraindication for live attenuated vaccines if CD4 levels are lower than 200 µL or there is AIDS.
- Patients with hyperlactatemia should avoid stavudine + didanosine treatment.
- Sexual dysfunction might require referral to specialists including a psychologist, urologist, cardiologist, or endocrinologist.
- Neurocognitive impairment might require central nervous system–active antiretroviral therapy.
- Hepatitis A, B, and C screening should occur in all patients.
Clinical Implications
- The recommendations for the initiation of antiretroviral therapy in patients who are HIV-positive without prior antiretroviral therapy exposure include an assessment of patients' readiness to begin antiretroviral therapy; all with a CD4 count lower than 350 cells/µL; a CD4 count 350 cells/µL or higher plus symptomatic HIV, pregnancy before third trimester, HIV-associated kidney disease, HIV-associated neurocognitive impairment, Hodgkin's lymphoma, human papillomavirus–associated cancers, or hepatitis B requiring anti–hepatitis B treatment; a CD4 count 350 to 500 cells/µL plus hepatitis B not requiring anti–hepatitis B treatment or hepatitis C for which anti–hepatitis C treatment is being considered, given, or not feasibleв
- Patients with HIV should be screened for the following conditions that can affect HIV management: pregnancy, tuberculosis, cancer, cardiovascular disease, hypertension, type 2 diabetes, dyslipidemia, depression, bone disease, vitamin D deficiency, kidney disease, increased alanine aminotransferase or aspartate aminotransferase, cirrhosis, lipodystrophy, travel, vaccination, hyperlactatemia, sexual dysfunction, neurocognitive impairment, and hepatitis A, B, and C.
