Isoniazid, d-drugs, weight, boost neuropathy risk in African trial

Isoniazid, stavudine (d4T), didanosine (ddI), higher weight, and older age all raised the risk of peripheral neuropathy in adults starting antiretroviral therapy (ART) in Uganda and Zimbabwe. Gender and pre-ART CD4 count did not affect chances of neuropathy in these DART trial participants.

Peripheral neuropathy—numbness, tingling, or pain usually starting in the toes—may be caused by HIV infection or some medications, including older nucleosides used to treat HIV. To determine neuropathy prevalence, incidence, and predictors in Ugandan and Zimbabwean adults starting a zidovudine-based antiretroviral regimen, DART trial investigators conducted this study.

DART was an open-label, multicenter, randomized trial of adults with symptomatic HIV infection starting their first antiretroviral regimen. Among 3316 trial participants, 421 self-reported peripheral neuropathy before starting ART for a prevalence of 13%.

Among 2895 people without neuropathy when the trial began, 354 (12%) took stavudine (as substitution for zidovudine) and 518 (18%) took isoniazid (a standard TB drug) during a median follow-up of 4.9 years. During follow-up neuropathy developed in 290 people (11%) for an incidence of 2.12 per 100 person-years (meaning neuropathy developed in about 2 of every 100 people every year). Eighteen people (0.1%) had grade 3 or 4 neuropathy.

Statistical analysis that accounted for several neuropathy risk factors identified five independent predictors of neuropathy at the following adjusted hazard ratios (aHR) (and 95% confidence intervals):

• Current stavudine: aHR 4.16 (3.06 to 5.66)
• Current didanosine: aHR 1.60 (1.19 to 2.14)
• Current isoniazid: aHR 1.59 (1.02 to 2.47)
• Higher pre-ART weight: aHR 1.07 per 5 kg (1.01 to 1.13)
• Older age: aHR 1.29 per 10 years (1.12 to 1.49)

Neither gender nor pre-ART CD4 count affected chances of peripheral neuropathy in this analysis.

“The incidence of peripheral neuropathy may now be lower in ART programmes, as stavudine and didanosine are no longer recommended,” the authors note.

They suggest that “all patients receiving isoniazid, either as part of antituberculosis chemotherapy or TB-preventive therapy, should receive pyridoxine as recommended in national guidelines.”

Source: Sylvia Kiwuwa-Muyingo, Bernard Kikaire, Ivan Mambule, Helen Musana, Godfrey Musoro, Charles F. Gilks, Jonathan B. Levin, Anne Sarah Walker. Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial. AIDS. 2014; 28: 2579-2588.

For the study abstract

(Downloading the complete article requires a subscription to AIDS or an online payment; the abstract is free.)

For more on peripheral neuropathy with HIV

Source: IAS

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By Mark Mascolini

Published: Dec. 24, 2014, 10:46 p.m.

Last updated: Dec. 24, 2014, 11:47 p.m.

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