Most ‘HAART-associated’ symptoms may not be attributable to drug therapy, study claims

Most clinical symptoms associated with highly active antiretroviral therapy (HAART) are as common in HIV-positive women on a stable HAART regimen as they are in HIV-positive women who have never taken HAART, according to a large cohort study presented in the August 16^th edition of Clinical Infectious Diseases. As all of the symptoms studied were more common in HIV-positive than HIV-negative women, the study suggests that the symptoms experienced by patients taking HAART may not be entirely attributable to drug treatment, but could be a direct consequence of HIV infection.

The study also showed that HIV-positive women changing their treatment regimen experienced more clinical symptoms than those on a stable regimen or who had never taken HAART, in agreement with previous findings.

Investigators examined the incidence of symptoms commonly associated with HAART in a group of patients enrolled in the Women’s Interagency HIV Study, a multicentre prospective cohort study based at six sites in the United States. Between April 2000 and April 2003, 364 HIV-negative and 1256 HIV-positive women completed a questionnaire at least once a year, which asked whether they had experienced any clinical symptoms in the previous six months.

The symptoms included were abdominal pain, diarrhoea, loss of appetite, nausea or vomiting, muscle pain, tiredness, fever, body fat redistribution, dizziness, headaches, paraesthesias (abnormal skin sensations), dryness of the mouth, kidney stones and rash. Each woman completed a mean of 4.7 questionnaires over the three-year study period.

The main findings were that:

• All 14 symptoms were more common in HIV-positive than HIV-negative women.
• Women who had been on a stable HAART regimen for at least six months had a higher risk of body fat redistribution and diarrhoea than HIV-positive women who had never taken HAART. Abdominal pain was less common in the stable HAART group. However, the occurrence of the eleven other symptoms was similar in the two groups, suggesting that they are not caused exclusively by HAART in HIV-positive women.
• Women who changed their HAART regimen had a higher occurrence of diarrhoea, nausea or vomiting, body fat redistribution, muscle pain and paraesthesias than HIV-positive women who had never used HAART. However, eight other symptoms occurred with similar frequency in the two groups, again suggesting their lack of a relationship to drug treatment.
• Among the women taking HAART, those with stable HAART regimens had the lowest risk of symptoms. This group reported less diarrhoea, loss of appetite, nausea or vomiting, fever, body fat redistribution, dizziness and dryness of the mouth than those who changed treatment.

The study’s authors argue that their findings “confirm the need to closely monitor the clinical symptoms of women on antiretroviral therapy,” particularly in those changing their drug regimen.

They conclude: “Our findings also reveal the need for caution in attributing clinical symptoms in HIV disease entirely to therapy use, given the high prevalence of symptoms among high-risk HIV-seronegative women and HAART-naïve HIV-seropositive women.”

However, the study did not stratify the participants according to the drugs being taken as part of their HAART regimens. It is therefore impossible to draw conclusions regarding the effect of individual drugs or drug classes, some of which may be associated with one or more of the symptoms analysed.

In the six months prior to each questionnaire, 49% of the HIV-negative women reported any clinical symptoms, in contrast to 67% of HIV-positive women not receiving therapy and 69% of those on HAART. Of the 14 symptoms included, all of which were significantly more common in the HIV-positive women (p

When the data from the women taking HAART were divided into those on a stable regimen in the last six months, those who had changed HAART regimen or those who had discontinued one or more drugs, the investigators discovered a significant effect of the use of HAART.

The women on a stable HAART regimen had a similar occurrence of symptoms to the HAART-naïve group (OR = 0.9; 95% CI: 0.7 – 1.1). In contrast, women who changed HAART regimen had a 1.4-times greater occurrence of any symptom (95% CI: 1.1 – 1.8) compared to those who had never taken HAART. Subsequent analysis revealed that this effect was significant for diarrhoea, nausea or vomiting, body fat redistribution, muscle pain and paraesthesias (p

The women who changed HAART regimen also had a greater occurrence of symptoms than those on a stable drug regimen (OR = 1.5; 95% CI: 1.2 – 1.9). This was found to be significant for diarrhoea, loss of appetite, nausea or vomiting, fever, body fat redistribution, dizziness, dry mouth and rash. A similar effect was seen in those who stopped HAART altogether (OR = 1.6; 95% CI: 1.3 – 1.9). “The highest prevalences for individual symptoms were observed among those who discontinued all medications and those who switched HAART regimen,” state the authors.

Although the authors point out that they cannot completely eliminate the effects of recall bias or clinical depression in their analysis, they argue that their study “attempts the most unbiased comparison possible of the prevalence of clinical symptoms in an observational cohort study.” Furthermore, to date, it is “the largest [study] to examine clinical symptoms in a cohort of HIV-seropositive and high-risk HIV-seronegative women.”