New HIV Guidelines Address Broad Range of Medical Conditions

Daniel M. Keller, PhD

October 24, 2013

BRUSSELS — Updated guidelines from the European AIDS Clinical Society (EACS) are a roadmap for the assessment and treatment of people infected with HIV. They go beyond HIV, and address the prevention and management of comorbidities, the management of chronic infection with hepatitis viruses, and the treatment of opportunistic infections.

Three experts presented the updated guidelines here at the 14th European AIDS Conference to a nearly packed auditorium.

One hot area is when to start antiretroviral therapy, said Nathan Clumeck, MD, from the Saint-Pierre University Hospital in Brussels, who is head of the antiretroviral section of the guidelines and cochair of the conference. It is "surprising to still be asking the question after so many years."

He referred to recent American and French guidelines that recommend beginning antiretrovirals for all HIV-infected people, and noted that the strength of the American recommendation is that it varies with CD4+ lymphocyte count and takes into account clinical condition, such as pregnancy, past AIDS-defining illness, hepatitis virus coinfection, risk for HIV transmission, and older age.

The EACS update differs from some other major guidelines because it takes a nuanced position on antiretrovirals.

The guidelines state that antiretrovirals should be considered and actively discussed with any person infected with HIV, even if that person is asymptomatic and has a CD4 count above 500/mm³. This clinical equipoise is intended to balance the benefits of viral suppression against the risks for adverse drug reactions.

In addition, they state that symptomatic infections or certain clinical conditions warrant a recommendation for therapy, not just a consideration.

The update addresses the public health issue of treatment as prevention to reduce the possibility of transmitting HIV to sexual partners. However, panelists at a news conference said they agreed that clinicians must serve the patient over the community at large, and that the patient's condition and desires must be primary.

The antiretroviral section of the guidelines includes information on adverse effects, interactions with other drugs (such as antidepressants, antihypertensives, and analgesics), dose adjustments for impaired hepatic or renal function, and administration of drugs for people with swallowing difficulties.

There is also information on switch strategies, which takes into account dosing simplification, better adherence, and prevention of or improvement in metabolic abnormalities. In addition, the guidelines lay out a strategy for antiretroviral initiation in patients coinfected with HIV and tuberculosis, based on CD4 count and drug–drug interactions, and provides a table of such interactions.

Managing Comorbidities

The aim of the section on the prevention and management of comorbidities was to provide recommendations based on levels of evidence and guidelines from outside HIV medicine, but "to not write a medical textbook," said George Behrens, MD, from the Hannover Medical School in Germany, who presented that section.

"We really welcome any comment you may want to make, whether positive or negative," he said, noting that the guidelines are a work in progress. The guidelines take into account differences in healthcare systems across Europe, but it was impossible to consider all aspects of the operation of all the systems, he explained.

Two new topics are addressed in the updated guidelines: the approach to fracture reduction and the sexual and reproductive health of men and women infected with HIV.

Dr. Behrens noted that bone disease and bone health are "very complex" issues. Tenofovir can exacerbate the decreased bone mass related to HIV, although how this affects fracture risk has not been established. Besides the intake of sufficient calcium and vitamin D and the appropriate use of bisphosphonates, the guidelines put reducing fall risks at the top of the list of measures to avoid fractures.

Reproductive health issues addressed include the sexual transmission of HIV, approaches to reproduction for serodiscordant couples who want to have children, screening and treatment of sexually transmitted infections, and sexual dysfunction.

The guidelines also deal with the general medical management of comorbidities.

It is recommended that treatment for hypertension begin with an ACE inhibitor, angiotensin-receptor blocker, or calcium-channel blocker, depending on patient age and ethnicity. Most patients will require more than 1 drug for adequate blood pressure control.

The diagnosis and management of diabetes are also addressed, especially in light of comorbidities and antiretroviral therapy. The guidelines note that glycated hemoglobin levels can be unreliable in the presence of hemoglobinopathies, high erythrocyte turnover, severe liver or kidney dysfunction, or older age, and when abacavir is used.

Finally, Dr. Behrens showed a rather extensive algorithm for the diagnosis and management of HIV-associated neurocognitive impairment in people without obvious confounding conditions. The algorithm begins with a 3-question screening test, and proceeds to more extensive neuropsychologic testing, brain imaging, and cerebrospinal fluid examination.

He said that future guidelines will likely address cancers and lung diseases.

Managing Hepatitis

Jürgen Rockstroh, MD, head of the HIV outpatient clinic at the University of Bonn in Germany, addressed the management of patients with hepatitis B virus and HIV coinfection. He presented an algorithm for treatment indications based on the usual tests for hepatitis B. However, when actual treatments are prescribed, other factors are taken into consideration, he noted, such as CD4 count, the specific antiretroviral administered, and whether the patient has symptomatic HIV disease.

He then discussed diagnostic procedures for people with hepatitis C virus and HIV coinfection, including serology, liver fibrosis assessment, and hepatitis C and IL28b genotypes. He noted that the new standard of treatment for newly diagnosed genotype 1 is a regimen of the direct-acting antiviral drugs boceprevir and telaprevir in combination with pegylated-interferon and ribavirin. These drugs are associated with toxic effects, so treatment can be delayed if fibrosis is absent or minimal because newer direct-acting antiviral drugs are expected soon. In addition, the guidelines contain a management strategy based on a 3 × 3 matrix of responder status (naïve, relapser, or nonresponder) and degree of fibrosis.

Dr. Rockstroh also discussed the treatment of other hepatitis C genotypes. Genotypes 2 and 3 respond well to pegylated interferon and ribavirin. Genotype 4 is similar to genotype 1, in that it is not sensitive to the current direct-acting antiviral drugs, but it appears to be susceptible to the next-generation drugs. With these agents, expected as soon as next year, "hepatitis C treatment will be easier to administer with better response rates," he noted, and a shorter treatment duration will probably become standard.

Dr. Clumeck reports financial relationships with Abbott Laboratories, Boehringer Ingelheim, Gilead Sciences, GlaxoSmithKline, MSD, Pfizer, Roche, and Janssen. Dr. Behrens reports financial relationships with Abbott, Boehringer Ingelheim, BMS, MSD, Gilead, and Janssen. Dr. Rockstroh reports financial relationships with Bionor, BMS, Boehringer Ingelheim, GlaxoSmithKline, ViiV, Abbott, Gilead, Pfizer, Merck, Tibotec, Roche, Novartis, and Janssen.

14th European AIDS Conference. Presented October 18, 2013.

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