Exercise intolerance may be due to impact of HIV treatment on heart

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The lowered tolerance of exercise seen among people taking HIV treatment may be an early manifestation of silent cardiac dysfunction, says a research letter published in the November 30th issue of AIDS. The report’s authors recommend regular cardiac assessment of patients on therapy, which may reveal subclinical abnormalities and help clinicians take steps to help patients preserve a healthy heart.

Experts have proposed several reasons for the lower tolerance to aerobic exercise seen among people with HIV taking HIV treatment, including smoking, anaemia and a loss of fitness as a result of living with a chronic disease. Some anti-HIV drugs, specifically nucleoside reverse transcriptase inhibitors (NRTIs), are also implicated because of the oxidative stress they place on the body’s tissues, including muscle.

Earlier in 2008, French investigators added another possible cause when they reported lower exercise tolerance and signs of dysfunction of the heart's left ventricle among a group of HIV-positive men. In the follow up study reported here, investigators probed the connection further. The study recruited 16 HIV-positive men (white, BMI 2, age 30 – 50 years) who had been on HIV treatment for at least two years and had well controlled disease (average CD4 cell count 503 cells/mm3 and an undetectable viral load in two-thirds of participants). Investigators compared them to a group of 21 HIV-negative men matched for age, size, smoking habits and activity level.


control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.


An interruption of blood flow to the brain, caused by a broken or blocked blood vessel. A stroke results in sudden loss of brain function, such as loss of consciousness, paralysis, or changes in speech. Stroke is a medical emergency and can be life-threatening.


A shortage or change in the size or function of red blood cells. These cells carry oxygen to organs of the body. Symptoms can include shortness of breath, fatigue and lack of concentration.


Describes an infection or disease which is not severe enough to present definite or readily observable symptoms.


In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

The investigators performed an echocardiogram (ECG) on the participants while they were at rest. The HIV-positive participants showed more frequent signs of cardiac dysfunction, particularly problems of the left ventricle during diastole (when the ventricle is refilling after contraction). Abnormalities in relaxation or filling were seen in 56% of the HIV-positive group, versus 14% in the control group (p > 0.01).

When participants then underwent a maximal exercise test, none of the men, HIV positive or negative, showed clinical signs of myocardial ischemia, or lack of blood flow to heart muscle. However, HIV-positive men had significantly lower performance on several indicators of cardiac function, even though both groups had similar smoking and activity levels and mean haemoglobin values.

Maximum cardiac output was 14% lower (p ≤ 0.05) in the HIV-positive group than the control group. Maximal heart rate was 6% lower in the HIV-positive group (p

Instead, the investigators suggest that the silent cardiac dysfunction observed during resting ECGs is the likely cause of exercise intolerance. In the HIV-negative group, stroke volume, or how much blood the heart pumps out during a single contraction cycle, increased until moderate intensity exercise, then reached a plateau. In HIV-positive men, stroke volume increased and then gradually decreased as participants went from moderate exercise to exhaustion, indicating decreased performance. Importantly, the investigators say, this pattern was seen specifically in men who had earlier shown signs of resting left-ventricle dysfunction.

The investigators also noted that compared with the HIV-negative control group, oxygenation levels in thigh muscle tissue were significantly lower only in HIV-positive men with resting cardiac dysfunction. They argue that this lack of oxygen was due to the central cardiac dysfunction and not due to disrupted oxygen metabolism in the tissue because there were no differences in the amount of oxygen consumed by tissues during exercise in both HIV-positive and HIV-negative groups. A previous study had suggested that exercise intolerance in people on HIV treatment is due to dysfunction in peripheral muscle tissue.

While acknowledging that larger studies are needed to better understand the causes of cardiac dysfunction, the investigators encourage closer monitoring for their patients on HIV treatment. “Cardiovascular risk assessment and regular cardiac screening (including echocardiography, ECG and exercise testing) should be considered in multitreated HIV-positive patients for early detection, prevention and follow-up.”


Thoni GJ et al. Silent cardiac dysfunction and exercise intolerance in HIV+ men receiving combined antiretroviral therapies. AIDS 22: 2537–40, 2008.