EACS 2017: New European Guidelines Cover HIV, Hepatitis C, and Related Conditions

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Everyone with HIV and hepatitis C virus (HCV) coinfection should receive direct-acting antiviral therapy for hepatitis C and should receive the same treatment regimens for hepatitis C as people with HCV monoinfection, new European guidelines issued at the 16th European AIDS Conference recommend.

[Produced in collaboration with aidsmap.com]

The guidelines, formulated by the European AIDS Clinical Society (EACS), are intended to set a standard of care for the entire European region including Eastern Europe. The guidelines are revised every 2 years and updated in between as new evidence arises.

The full guidelines document is available to download from the EACS website or as an app. The guidelines also include links to video tutorials on aspects of diagnosis and consultation.

Viral Hepatitis

The guidelines now recommend that people with HIV/HCV coinfection should receive the same direct-acting antiviral treatment for hepatitis C as people with HCV monoinfection. There is no need for longer courses of treatment, and the only HIV-specific consideration that should drive the selection of a regimen is the potential for drug-drug interactions.

In people who do not clear hepatitis C after a first course of direct-acting antiviral treatment, the guidelines recommend assembling a regimen after resistance testing.

Interferon-based therapy is no longer recommended for treatment of primary HCV infection.

A new algorithm guides physicians in determining when to treat acute HCV infection. Treatment should be initiated if HCV RNA has not fallen by at least 2 logs at 4 four weeks after diagnosis or if the patient still has detectable HCV RNA 12 weeks after diagnosis despite a 2-log reduction at week 4.

Antiretroviral Therapy

There are no changes in the first-line antiretroviral regimens recommended in the 2017 guidelines, except for a downgrading of atazanavir/ritonavir.

EACS continues to recommend that first-line treatment should be based on tenofovir and emtricitabine or abacavir and lamivudine, with the use of tenofovir alafenamide (TAF) preferred over tenofovir disoproxil fumarate (TDF) in cases where there is an established or high risk of chronic kidney disease; co-medication with nephrotoxic drugs or prior TDF toxicity; osteoporosis, progressive osteopenia or bone loss risk factors; or a history of fragility fractures.

All integrase inhibitors, the non-nucleoside reverse transcriptase inhibitor rilpivirine (Edurant) and the boosted protease inhibitor darunavir (Prezista) are the preferred third agents for first-line treatment. Atazanavir/ritonavir has been downgraded to an alternative option due to the frequency of kidney toxicity in people taking the drugs.

The combination of dolutegravir (Tivicay) and rilpivirine (coformulated in the new Juluca combination pill in the U.S.) has been added as a switch option, but the guidelines stress that dolutegravir monotherapy should not be used as a switch option due to the high risk of viral rebound and cross-class drug resistance.

Solid Organ Transplantation

A new section on solid organ transplantation has been added to the guidelines. The guidelines panel states that people living with HIV should be considered for organ transplantation using the same indications as for HIV-negative people.

Non-Alcoholic Fatty Liver Disease

New guidance on the management of non-alcoholic fatty liver disease has been added, following findings showing that around half of people with HIV referred for investigation after abnormal liver function tests turn out to have NAFLD.

NAFLD consists of a spectrum of liver damage caused by metabolic disorders and lifestyle factors highly prevalent in people living with HIV, including obesity, high cholesterol and triglyceride levels, diabetes, and other metabolic disorders. These disorders lead to fat accumulation in the liver and may eventually progress to the development of fibrosis -- non-alcoholic steatohepatitis (NASH) -- and inflammation -- and cirrhosis in a minority of people. The high prevalence of NAFLD in people living with HIV (up to 30%-40% in US cohorts) means that the prevalence of fibrosis and cirrhosis in people without risk factors for viral hepatitis or chronic alcohol abuse will also be higher in this population.

Diagnosis of NAFLD in people with abnormal liver function and no viral hepatitis or history of excessive alcohol use should be carried out by ultrasound, with biopsies to confirm NASH in more advanced cases. Ultrasound imaging of the liver should also be considered for people with metabolic syndrome and no other risk factors for fibrosis and normal liver enzymes, with repeat follow-up every 2 to 5 years depending on the presence of steatosis (fat accumulation in the liver).

Lifestyle modification to reduce weight and metabolic risk factors is the cornerstone of treatment. Lipid-neutral antiretroviral regimens should also be considered as a means of modifying metabolic risk factors.

Chronic Lung Disease

The guidelines include new recommendations on chronic lung disease including chronic obstructive pulmonary disease (COPD).

Low CD4 count can exacerbate COPD, but it is the high prevalence of smoking among people with HIV that makes chronic lung disease a growing problem as the HIV-positive population ages.

EACS recommends that all people with HIV should be screened for chronic lung disease if they are age 40 or over or if they have smoked for the equivalent of 10 years. Regular wheezing, cough, or shortness of breath on exertion should prompt further investigation to diagnose COPD. If symptoms do not improve with use of a single bronchodilator, further treatment should be tailored to symptoms.

There is no evidence that use of oral glucocorticoids has benefit in COPD, and inhaled glucocorticoids should not be used with boosted antiretroviral regimens. Influenza and pneumococcal vaccinations are proven to reduce the incidence of lower respiratory tract infections. Smoking cessation is a lifesaving intervention for this population.

HPV

Human papillomavirus vaccination is now recommended for everyone living with HIV under age 26 and all men who have sex with men up to the age of 40. HPV is a sexually transmitted virus that causes genital warts, and some types can leads to the development of cervical, anal, and oropharyngeal cancers. Anal cancer, rare in the general population, is becoming more common among people living with HIV, especially men who have sex with men.

Deborah Konopnicki of St. Pierre University Hospital in Brussels presented a review of the evidence supporting vaccination against HPV in people living with HIV at last month’s European AIDS Conference in Milan.

Screening for HPV-related cancers is inconsistent, and for anal cancer, the choice of screening technique is still a matter of debate, she said. As for oropharyngeal cancers caused by HPV, whether to screen for these conditions is still unclear.

Greater use of preventive vaccines has the potential to reduce HPV-associated morbidity. Vaccination of girls and young women has resulted in significant reductions in HPV-associated morbidity in Australia, Denmark, and Scotland, within 10 years of the first vaccination programs.

Only one study, the ACTG 5298 study, has looked at the effect of vaccination on protection against HPV infection in HIV-positive adults. That study found that in a predominantly male population with a median age of 47 years, vaccination did not reduce persistent infection with HPV.

This finding led EACS to recommend that HPV vaccination should be offered to people with HIV age 26 and under. EACS has also followed the British HIV Association in recommending vaccination for all men who have sex with men with HIV under the age of 40. Previous guidance issued in 2015 recommended that doctors should follow national guidance on HPV vaccination.

Although EACS states that the efficacy of the vaccine is questionable in people who have already been exposed to HPV, Konopnicki said it is still plausible that vaccination could improve protection against HPV-associated disease.

The ACTG A5240 study showed that among women who were already seropositive for any of the HPV types included in the quadrivalent vaccine (Gardasil), vaccination resulted in a substantial increase in HPV antibody titers (+1.5 log10 IU/ml).

There is also some evidence from studies in HIV-negative women and men who have sex with men that vaccination after the treatment of HPV-associated cervical or anal lesions is associated with reductions in recurrence of lesions.

Two ongoing studies are likely to provide further information on the role of vaccination in preventing recurrence in people living with HIV.

Vaccination results in greater antibody responses in women living with HIV who already have undetectable HIV viral load at the time of the first vaccination, probably because viral suppression permits immune restoration.

EACS recommends the 9-valent HPV vaccine (Gardasil 9), active against nine common types of HPV, if available). Konopnicki noted that there is no evidence in people with HIV to support anything less than a 3-dose vaccination schedule, although several studies of young women have shown that a single dose is just as immunogenic as multiple doses.

Anal Cancer

Research from Austria presented at the conference by Robert Zangerle of the Medical University in Innsbruck showed that by 2015, anal cancer had already affected at least 1 in 40 men who have sex with men receiving care in clinics affiliated to the Austrian HIV Cohort Study. Zangerle said that the rate was already "alarmingly high."

The cohort covers around three-quarters of people receiving HIV care in Austria (7511 people). Between 2003 and 2015, 46 cases of anal cancer were diagnosed, 63% in men who have sex with men. The overall incidence was 52.5 cases per 100,000 person-years of follow-up, but was higher among men who have sex with men (95.1 per 100,000 person-years) and lower among women (36.5 per 100,000 person-years).

By 2015, 0.8% of men who have sex with men in care who were under the age of 50 had ever been diagnosed with anal cancer, but the cumulative prevalence rose to 2.6% among gay and bi men over the age of 50, and 1.6% among women with HIV age 50 and over. In summary, the Austrian cohort study found that 1 in 40 gay and bi men with HIV age 50 and over had already been diagnosed with anal cancer. The median age of the over-50 age group was 56 years, suggesting that anal cancer could continue to be a significant cause of disease as these men age.

11/30/17

Source

European AIDS Clinical Society. EACS Guidelines 9.0. 2017.