Starting HIV treatment doesn't increase neuropathy rate in Thai study

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A small Thai study has found identical rates of neuropathy between patients taking HIV treatment and those yet to start antiretroviral therapy. The study is published in the December 1st edition of the Journal of Acquired Immune Deficiency Syndromes.

Most of the patients being treated with antiretroviral drugs were taking d4T (stavudine, Zerit), making this finding surprising.

There are two major causes of neuropathy in patients with HIV. The first is a weak immune system and it is estimated that 30% of HIV-positive individuals will develop neuropathy unless they receive treatment with antiretroviral drugs. However, neuropathy can also be a side-effect of some nucleoside reverse transcriptase inhibitors (NRTIs), most notably d4T, a drug that is widely used in resource-limited settings. Previous research in Thailand suggested that 7% of patients taking a d4T-containing regimen developed neuropathy within two years of starting HIV treatment.

Glossary

neuropathy

Damage to the nerves.

treatment-naive

A person who has never taken treatment for a condition.

naive

In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

treatment-experienced

A person who has previously taken treatment for a condition. Treatment-experienced people may have taken several different regimens before and may have a strain of HIV that is resistant to multiple drug classes.

AIDS defining condition

Any HIV-related illness included in the list of diagnostic criteria for AIDS, which in the presence of HIV infection result in an AIDS diagnosis. They include opportunistic infections and cancers that are life-threatening in a person with HIV.

To gain a better understanding of the prevalence and risk factors of neuropathy, investigators from the Phramongkutkloa Medical Centre in Bangkok designed a cross-sectional study involving 100 HIV-positive patients, 63 of whom were taking HIV treatment. Recruitment took place between January and July 2006.

Information was obtained from their medical records about the presence of other illnesses, history of AIDS-defining illnesses, use of antiretroviral drugs, CD4 cell counts and viral load.

A number of tests were conducted to see if patients had sensory impairment associated with neuropathy and neuropathy-associated symptoms such as numbness and pain.

Median CD4 cell count was 132 cells/mm3 and 37% of patients had been diagnosed with an AIDS-defining illness, the most common being tuberculosis (19%).

Of the 63 patients taking antiretroviral therapy, 61 were taking a d4T-containing regime.

Unsurprisingly, patients taking antiretroviral therapy had a higher CD4 cell count (213 cells/mm3 vs. 44 cells/mm3, p

Symptoms suggestive of neuropathy were present in an identical proportion of treatment-experienced and treatment-naive patients (35%). However, none of the treatment-naive patients reported neuropathic pain but this symptom was reported by seven of the patients taking anti-HIV drugs.

Further more, a similar proportion of patients taking HIV treatment (28%) and treatment-naive patients (32%) had possible sensory impairment associated with neuropathy. When the investigators used the strictest-possible definition of sensory impairment they once again found that a similar proportion of treatment-experienced and treatment-naive patients had this condition (9.5% vs 10.6%).

A lower CD4 cell count was associated with an increased risk of neuropathy overall.

“It is interesting to note a lack of divergence in probably HIV-associated sensory neuropathy rates by antiretroviral status,” write the investigators. They add, “this finding is unexpected considering the high frequency of dNRTI use (94%), a factor expected to increase rates of antiretroviral toxic neuropathy.”

The investigators hypothesise that in their cohort “the tendency for dNRTI to induce neuropathy may have been outweighed by the favorable effects of immunologic benefit with potent antiretroviral therapy, particularly because our cohort had severe immunosuppression.”

An association between a low CD4 cell count and a higher risk of neuropathy in antiretroviral-treated patients has also been found in other research. The investigators therefore suggest “immunologic parameters continue to be important as a risk factor for HIV sensory neuropathy after use of potent antiretroviral medications.”

They conclude by calling for more research to determine rates of neuropathy after the initiation of antiretroviral regimens.

References

Sithinamsuwan, P. et al. Frequency and characteristics of HIV-associated sensory neuropathy among HIV patients in Bangkok, Thailand. J Acquir Immune Defic Syndr 49: 456-58, 2008.