Peripheral artery disease

Peripheral artery disease is the second most common form of cardiovascular disease after coronary artery disease. Arteries in the lower limbs or supplying major organs become narrowed as a result of deposits of cholesterol. Blood supply to the limbs is reduced, leading to cramping or pain in the leg and hip muscles during activity, especially walking. As peripheral artery disease progresses, pain may become more persistent. In its most advanced form, peripheral artery disease can lead to tissue damage and gangrene in the limbs, possibly requiring amputation.

Numbness in the limbs, sores on the legs or feet, pale or blue skin on the legs or hair loss on the legs and feet are also symptoms of peripheral artery disease. The condition is more common in men and may progress for a long time without symptoms. Peripheral artery disease can be diagnosed by comparing the blood pressure at the ankle and the arm; lower blood pressure at the ankle, caused by a restricted blood supply, indicates peripheral artery disease.

People who develop peripheral artery disease are at high risk for a stroke or heart attack. Peripheral artery disease is already present in around one in twenty people in the 45-50 age group and the risk increases with age and in people with other risk factors for cardiovascular disease, especially smoking or diabetes.

Stopping smoking and taking regular exercise can improve the condition, as can reduction of cholesterol, blood sugar and blood pressure through lifestyle and dietary changes and medication.

A large study of US military veterans living with HIV presented at last month’s IAS Conference on HIV Science (IAS 2017) showed that people living with HIV with CD4 counts below 500 were at higher risk of developing peripheral artery disease than people without HIV of the same age and ethnic group, after taking into account smoking, lipid levels and other risk factors for cardiovascular disease.

The risk was approximately 24% higher for people with CD4 counts between 500 and 200 and 73% higher for people with CD4 counts below 200.

The findings underline the importance of starting treatment as soon as possible after diagnosis, especially in older people, as well as the protective effect of a high CD4 cell count.

Anal cancer

Anal cancer will be seen less frequently in the future among men who have sex with men who are living with HIV, due to universal treatment of HIV infection, Swiss researchers predict, based on an analysis of the incidence of the cancer and risk factors for anal cancer in Swiss men who have sex with men living with HIV.

Anal cancer is caused by cancer-causing strains of human papillomavirus (HPV), especially HPV-16. It is a rare cancer in the general population in comparison to lung cancer, bowel cancer and prostate cancer, the most common types of cancer diagnosed in men. But, incidence of anal cancer among HIV-negative gay men is 5 cases per 100,000 person-years, about five times higher than the rate observed in the general population. Anal cancer is even more common among HIV-positive gay men, with an estimated incidence between 78 and 168 cases per 100,000 person-years.

As a consequence, prevention, detection and treatment of anal cancer are important elements of HIV care.

Known risk factors for anal cancer in HIV-positive gay men are persistent infection with high-risk HPV strains, smoking and a low CD4 cell count.

More widespread use of antiretroviral treatment has resulted in improvements in CD4 cell counts and cases of anal cancer appear to have peaked among men who have sex with men with HIV. The Swiss researchers project that the incidence of anal cancer will fall from 82 cases per 100,000 person-years to 59 cases per 100,000 person-years in 2030. Universal HIV treatment and annual screening for anal cancer using anoscopy would reduce the incidence further, to 31 cases per 100,000 person-years in 2030.

The researchers say that based on incidence in their cohort, screening for anal cancer in men who have sex with men with HIV would be just as cost-effective as screening for cervical cancer in women, and the best methods for screening ought to be investigated further.

For more information, read NAM's factsheet 'Anal cancer'.

Switching to dolutegravir

Prolonged use of a boosted protease inhibitor may lead to higher lipid levels and an increase in cardiovascular disease risk, particularly in older people and those with other risk factors for cardiovascular disease such as hypertension or diabetes.

Integrase inhibitor treatment results in smaller increases in cholesterol but it has been unclear whether or not switching from a boosted protease inhibitor to the integrase inhibitor dolutegravir (Tivicay) can improve the lipid profile and potentially reduce the risk of cardiovascular disease.

A study presented at last month’s IAS 2017 conference showed that cholesterol levels fell in people at higher risk of heart disease who switched from a boosted protease inhibitor to dolutegravir. Forty-eight weeks after switching, those receiving dolutegravir had experienced reductions in total and LDL ('bad') cholesterol of 7 to 8%, whereas cholesterol levels remained unchanged in people taking a boosted protease inhibitor.

Boosted darunavir and lamivudine

Reducing the number of drugs used in HIV treatment has the potential to reduce long-term side-effects and to cut costs. Several preliminary studies have looked at the potential for cutting the number of drugs used in first-line treatment from three to two, by combining a powerful boosted protease inhibitor or integrase inhibitor with the cheap nucleoside reverse transcriptase inhibitor (NRTI) lamivudine.

At last month’s IAS 2017 conference early results from the ANDES study showed that a combination of darunavir/ritonavir and lamivudine was just as effective as the same combination plus tenofovir in previously untreated people.

The Argentinean researchers who designed the ANDES study were interested to test darunavir/ritonavir in a two-drug combination because a generic equivalent is already manufactured in Argentina. Generic versions of darunavir could become available in Europe after patents begin to expire in 2017.

Darunavir boosted by ritonavir or cobicistat is recommended as an option for first-line treatment in combination with two NRTIs in United States and European treatment guidelines due to its high barrier to resistance.

In the ANDES study, 97% of people taking a three-drug regimen and 95% of people taking the two-drug regimen had an undetectable viral load after 24 weeks on treatment. The study is ongoing and will recruit more people to compare the two regimens over a longer follow-up period.

At the same time, two large studies are testing a two-drug regimen of the integrase inhibitor dolutegravir combined with lamivudine against a three-drug regimen that also includes tenofovir. If these studies show that two-drug regimens are just as good as three-drug regimens in previously untreated people, treatment guidelines may shift to recommending two-drug regimens.