Side-effects

The most common side-effects of abacavir (Ziagen) are nausea, vomiting, lethargy, and fatigue. Other commonly reported side-effects are fever, headache, diarrhoea, and loss of appetite. In general, symptoms appear in the first few weeks of treatment, are mild to moderate in severity, and tend to resolve on their own.

Abacavir seems to be less damaging to mitochondria than some of the other nucleoside reverse transcriptase inhibitors (NRTIs), such as stavudine (d4T, Zerit) and zidovudine (AZT, Retrovir).¹ It is therefore less likely than some of the other NRTIs to cause side-effects related to mitochondrial damage, such as fat loss from under the skin.² A number of studies have examined the effects of switching from these drugs to abacavir, with most showing modest improvements in fat levels.^{3 4 5}

There is conflicting evidence as to whether abacavir increases the risk of myocardial infarction. Recent data on this issue are described below.

Lactic acidosis is a rare, but serious side-effect of all NRTIs including abacavir. Symptoms include an enlarged and tender liver, nausea, and malaise. Lactic acidosis usually develops within a few months of starting treatment with NRTIs. This side-effect seems to occur more commonly in women and in individuals with existing liver disease or who are obese.

Liver toxicity was reported in two women 10 to 12 weeks after switching to an abacavir-containing regimen. Neither had underlying risk factors for liver disease and both tested HLA-B*5701 negative before starting the drug. Laboratory values were normal at six weeks, but alanine aminotransferase (ALT) were well over five times the upper limit of normal a short time later. The one biopsy done found severe inflammation in one women. Hypersensitivity reaction and hepatitis were both ruled out as causative agents. Lab values returned to normal and Inflammation resolved after treatment with abacavir was stopped. The authors point out that even minor symptoms after starting therapy should be reported and investigated.⁶

Three case reports of changes in mental state in people starting abacavir have been reported. Although rare, symptoms include depression, suicidal thoughts, auditory hallucinations, psychosis, headaches and nightmares.^{7 8 9}

There is conflicting evidence regarding the impact of abacavir use on the risk of cardiovascular disease.

In 2009, D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) investigators presented information collected from over 33,000 participants from 11 prospective cohorts. They found that recent abacavir use (in the past six months) increased the risk of myocardial infarction by 68%; that risk rose with correspondingly longer time on abacavir.¹⁰

Results from SMART (Strategies for Management of Anti-Retroviral Therapy) study also found an excess risk of cardiovascular disease with abacavir use as compared to other NRTIs. Events included myocardial infarction; stroke, coronary artery disease, congestive heart failure, peripheral vascular disease, and death. Researchers believe that abacavir may cause vascular inflammation, increasing the risk of cardiovascular events, particularly in those already highly vulnerable.¹¹

A subsequent systematic review of studies looking at the relationship between antiretroviral drugs and cardiovascular disease found that the evidence of an association between recent exposure and cumulative exposure to abacavir and heart attack was mixed.¹² The lack of consistency in findings is due to differing inclusion criteria, varying ages of cohorts and lack of statistical power to measure significant differences in events. As a consequence of the uncertainty, the British HIV Association has concluded that abacavir should be avoided wherever possible by people with a high risk of cardiovascular disease.