Treatment Outcomes of Patients with HIV and Tuberculosis

In a retrospective study of 700 patients with culture-positive tuberculosis (TB), relapse rates were found to be significantly higher in HIV-infected patients compared to HIV-uninfected patients following a rifamycin-based regimen. Furthermore, TB relapse rates were higher in HIV-infected patients who received intermittent or standard 6-month therapy when compared to those receiving daily or longer treatment.

The results appear in the first issue for June 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.Payam Nahid, M.D., M.P.H., of the University of California, San Francisco General Hospital, and eight associates reviewed TB cases reported to the San Francisco Tuberculosis Control Program from January 1, 1990, through December 31, 2001. As a rationale for their study, the researchers state that the optimal duration of TB therapy in HIV-infected subjects is unknown and may differ from HIV-uninfected individuals.According to the authors, the current preferred regimen for treating drug-susceptible TB in HIV-uninfected patients is a 6-month, rifamycine-based regimen that includes pyrazinamide during the first two months. Current guidelines for the treatment of TB do not distinguish between those infected with the virus that causes AIDS and those who are uninfected in terms of the optimum length of treatment when using rifamycine.”Standard 6-month therapy may be insufficient to prevent relapse in patients with HIV,” said Dr. Nahid.The TB relapse rate for HIV-infected patients was found to be 6.6 percent versus 0.8 percent in uninfected/unknown patients. This finding was in contrast to other studies that did not find any significant difference between HIV-infected and HIV-uninfected/unknown patients. However, this finding was corroborated by a similar study that also used molecular genotyping as a relapse indicator. HIV-infected patients who received 6 months of rifamycin-based TB treatment or who were treated intermittently (one to three times per week), were four times more likely to have a reoccurrence than those r who took their medicine daily or who were treated for longer periods.The study also found that the use of highly active antiretroviral therapy (HAART) during TB treatment was associated with a faster Mycobacterium tuberculosis negative culture conversion, and an improved survival rate. Prior studies by others have shown HAART treatment beneficial in preventing TB in HIV-infected individuals, but reported no beneficial TB treatment outcomes. HIV-infected patients were significantly more likely to develop drug resistance (4.2 percent in HIV-infected versus 0.5 percent in HIV-uninfected) to rifampin , and to experience adverse reactions to TB regimens. The investigators noted that there is a need for large randomized clinical trials to establish the optimal duration for TB therapy in HIV-infected patients, and the timing of HAART treatment in patients with HIV-related TB. According to an editorial commenting on the research in the same issue of the journal, future HIV-related TB treatment regimens and relapse studies should broaden their focus to include rates of acquired drug resistance. The editorial cites a report published in the Lancet of an extensively drug resistant TB strain found in a HIV co-infected South African patient as particularly worrisome. Citing the journal article, the editorialists also cast the HAART findings (quicker reduction of mycobacterial burden) as relevant in deterring TB drug resistance. They suggest that short-course, intermittent regimens may be necessary in areas where resources are limited, and that additional research on regimens (including the use of second line drugs) suitable for field use must continue.Study Explains Why Patients with Obstructive Sleep Apnoea Are At Higher Risk for Cardiovascular DiseaseResearchers have found that patients with obstructive sleep apnoea (OSA) have higher levels of a type of dead cells (apoptotic cells) from the lining (endothelium) of their blood vessels circulating in their bloodstream than people who do not have OSA. The finding may help explain why those with OSA are at higher risk for cardiovascular disease (CVD).According to the researchers, “levels of apoptotic endothelial cells are correlated with abnormal endothelial vasorelaxation, a precursor of atherosclerosis-related events,” and that treatment with nasal continuous positive airway pressure (nasal CPAP) can reduce levels of circulating apoptotic endothelial cells in OSA patients.These findings appear in the June 1 issue of the American Journal of Respiratory and Critical Care Medicine, a publication of the American Thoracic Society.Lead researcher Ali El Sohl, M.D., M.P.H., said the study was done “to explain why patients with OSA had a higher risk of cardiovascular morbidity and mortality.” He added that “the increased levels of circulating apoptotic endothelial cells would mean less production of nitric oxide that is crucial to artery vasodilatation. The less nitric oxide, the higher potentially is the risk of hypertension and acute heart attack. CPAP treatment would likely restore the physiologic function of the lining of the blood vessels.”For the study, 14 men with OSA were recruited from the Sleep Clinic at the Erie County Medical Center, a hospital affiliated with the University of Buffalo, in New York. The patients were nonsmokers without any coexisting diseases, and they did not use medications. Ten healthy nonsmokers were recruited from a wellness clinic at the same hospital to serve as controls.The OSA patients were given polysomnographic testing to verify the diagnosis. This involved evaluating brain waves, electrical activity of muscles, eye movements, breathing rates, blood pressure, blood oxygen saturation and heart rhythm, as well as direct observation of patients during sleep.The men were comparable in age, blood pressure and metabolic profiles, but the OSA patients had a higher body-mass index, though the difference was not statistically significant. The OSA patients also had more apoptotic cells circulating in their bloodstreams and had vasomotor dysfunction.The OSA patients were given nasal CPAP treatment for eight weeks. Use of CPAP ranged from four to seven hours per night. At the end of the study, the patients’ vascular reactivity and circulating endothelial apoptotic cells were reevaluated and compared to the controls.There were no significant differences in body measurements and metabolism in the men from baseline, but most of the patients who received CPAP had reduced circulating endothelial apoptotic cells and had marked improvements in brachial artery vascular reactivity.The study had some limitations. Women were excluded to keep the study population homogeneous. Said Dr. El Sohl, “a follow-up study would be required to look at this phenomenon in women and in particular the hormonal effect on apoptosis in OSA.” The researchers “did not perform a thorough assessment for excluding coronary disease.”More research is needed before these results can be applied clinically, according to Dr. El Sohl. While CPAP is currently used to treat OSA, looking for circulating apoptotic endothelial cells as a marker to fine-tune the therapy is one potential application. This may potentially reduce OSA patients’ risk of CVD. Dr. El Sohl mentioned that statins, angiotensin converting enzyme inhibitors, and vitamin C reduce enthothelial apoptosis, but it is not known if these agents could help patients with OSA.According to Dr. El Sohl, further research will investigate if the improvements in vascular function correlate with actual improvements in the sleep patterns of patients with OSA(Source: American Thoracic Society : American Journal of Respiratory and Critical Care Medicine : June 2007)