Tuberculosis remains a serious AIDS-defining illness in the HAART era, and remains problematic to treat, according to a variety of presentations and publications appearing this week.
In a study published in the January 4, 2002 edition of the journal AIDS, clinicians in London report on the treatment of tuberculosis in 188 HIV-positive patients diagnosed with TB between 1996 and 1999. The study reviewed a cohort of patients treated at 12 hospitals in London, and was not randomised. 64% were heterosexuals exposed to HIV outside the UK, an 41% were unaware of their HIV status at the time of TB diagnosis. Almost half presented with extrapulmonary TB (TB outside the lung).
They found that individuals were presenting with TB at low CD4 cell counts (median of 94), and that individuals diagnosed with CD4 cell counts below 100 cells/mm3 were more likely to develop subsequent AIDS-defining illnesses (39% developed a subsequent illness during the period of TB therapy). The authors of the study recommended that anyone with a CD4 cell count below 100 at the time they are diagnosed with TB should begin HAART immediately, regardless of an increased risk of adverse events.
Over half (54%) were not prescribed antiretroviral therapy during their TB therapy, while 18% were already on antiretroviral treatment when they were diagnosed with TB. The remainder began highly active antiretroviral treatment an average of two months after starting TB treatment, with numbers almost evenly split between those who started a PI-containing regimen and those who started an NNRTI-containing regimen.
Patients receiving TB therapy and HAART at the same time were around 90% more likely to experience adverse events (OR 1.88), and women were twice as likely to experience adverse events as men (OR 2.03). Adverse events led to the discontinuation or interruption of TB and/or HIV therapy, and consequent extensions of TB therapy beyond the normal six month period. Adverse events related to TB therapy were most likely to occur in the first two months, leading the authors to recommend that it may be better to delay the introduction of HAART for two months after beginning TB treatment in patients with CD4 cell counts above 100.
Peripheral neuropathy occurred at a higher rate in TB patients than previously seen in HIV patients commencing HAART; 21% developed peripheral neuropathy, of whom just over half (56%) were taking antiretrovirals. However, there was no significant difference in the risk of developing peripheral neuropathy when those taking isoniazid with or without d4T were compared (although a trend towards a higher risk in the d4T group was apparent).
In a presentation at the 41st Annual Interscience Conference on Antimicrobial and Antiviral Chemotherapy (ICAAC) this week in Chicago, Dr Larry Teeter of Baylor College of Medicine in Houston, Texas, reported that alone amongst AIDS-defining infections, TB incidence has remained stable since 1996, with HIV-positive patients being diagnosed with TB with a median CD4 cell count of 174 cells/mm3 in Houston.
A Spanish group reported that multi-drug tuberculosis may occur more frequently in HIV-positive people with low CD4 cell counts. The group conducted a retrospective analysis of an MDRTB outbreak that occurred in 1994 in Madrid. Of 266 HIV patients exposed to people with MDRTB, 7.5% developed MDRTB, and these individuals were significantly more likely to have a CD4 cell count below 100 cells/mm3 at the time of exposure (p=0.035) (Cobo).
A small French cohort study (n=50) reported that patients who received NNRTIs as HIV therapy while on TB treatment had significantly better viral load control than patients who received protease inhibitors, but the control over viral load exerted by the HAART regimen had no impact on the rate of TB cure (Martinez).
References
Cobo J et al. Impact of CD4 count at the time of exposure to multi-drug resistant tuberculosis (MDRTB) in the risk of developing MDRTB among HIV-infected subjects. 41st ICAAC, Chicago, abstract 246, 2001.
Dean GL et al. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS 16: 75-83, 2002.
Martinez V et al. HIV infection and tuberculosis: PIs or NNRTIs? 41st ICAAC, Chicago, abstract 245, 2001.
Teeter LD et al. The effect of highly active antiretroviral therapy (HAART) on tuberculosis incidence in Houston, TX. 41st ICAAC, Chicago, abstract 244, 2001.