Rates and risk factors for nephrotoxicity and ototoxicity among tuberculosis patients in Tbilisi, Georgia.

SETTING: Treatment of multidrug-resistant tuberculosis (MDR-TB) is lengthy and utilizes second-line anti-TB drugs associated with frequent adverse drug reactions (ADRs).OBJECTIVE: To evaluate the prevalence of and risk factors for ADRs among patients with MDR- and extensively drug-resistant TB (XDR-TB).DESIGN: A retrospective chart review of patients initiating treatment for M/XDR-TB in 2010-2012 in Tbilisi, Georgia.RESULTS: Eighty (54%) and 38 (26%) of 147 patients developed nephrotoxicity per RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) classification and ototoxicity, respectively. Twenty-five (17%) patients required permanent interruption of injectables due to an ADR. Median hospital stay, total treatment duration and number of regimen changes were higher among those with nephrotoxicity and/or ototoxicity, compared to those without (P < 0.01). Multinomial logistic regression analysis identified increasing age (per year) as a risk factor for nephrotoxicity (aOR 1.08, 95%CI 1.03-1.12) and for both, nephro- and ototoxicity (aOR 1.11, 95%CI 1.05-1.17). Low baseline creatinine clearance (CrCl) was a significant risk factor for developing nephrotoxicity (aOR 1.05, 95%CI 1.02-1.07).CONCLUSION: Second-line injectable drug-related ADRs are common among M/XDR-TB patients. Patients with increasing age and low baseline CrCl should be monitored closely for injectable-related ADRs. Notably, our findings support WHO's latest recommendations on introduction of injectable free anti-TB treatment regimens.

Alcohol use and the management of multidrug-resistant tuberculosis in Tomsk, Russian Federation.

SETTING: Alcohol use increases the risk of multidrug-resistant tuberculosis (MDR-TB) and poses challenges for successful MDR-TB treatment, including the potential for additional adverse events. AIM: To investigate the association between alcohol consumption during MDR-TB treatment and adverse events and treatment outcomes in a cohort of patients in Tomsk, Russia. DESIGN: From 2000 to 2004, retrospective data were collected on 407 MDR-TB patients in Tomsk. Factors associated with treatment outcomes were assessed using logistic regression. RESULTS: Of the 407 patients, 253 (62.2%) consumed alcohol during treatment ('drinkers'), and 367 (90.2%) had at least one documented adverse advent. No significant differences were noted in frequency of adverse events in drinkers vs. non-drinkers. Drinkers had less favourable treatment outcomes (OR 0.28, 95%CI 0.18-0.45). Among drinkers, favourable treatment outcome was associated with adherence to at least 80% of prescribed doses (OR 2.89, 95%CI 1.30-6.43) and the occurrence of an adverse event requiring treatment interruption (OR 2.49, 95%CI 1.11-5.59). CONCLUSIONS: Alcohol use did not appear to increase the risk of adverse events during MDR-TB treatment; however, alcohol consumption was associated with poor outcome. Our findings suggest that individuals who drink alcohol should receive aggressive attention to optimise treatment adherence and manage adverse events.

Hepatotoxicity during treatment for multidrug-resistant tuberculosis: occurrence, management and outcome.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment program in Tomsk, Russia. OBJECTIVE: To describe the incidence and management of hepatotoxicity during treatment of MDR-TB, and to assess risk factors associated with its development and impact on treatment outcomes. DESIGN: A retrospective case series performed among 608 patients. RESULTS: Hepatotoxicity, using American Thoracic Society (2006) definitions, was observed in 91/568 patients (16.5%). The median time to the first hepatotoxic event was 196 days post treatment commencement. Baseline factors associated with hepatotoxicity included elevated alanine aminotransferase/aspartate aminotransferase/bilirubin (OR 53.9, 95%CI 6.30-438.7), and renal insufficiency (OR 19.6, 95%CI 2.71-141.6). High treatment adherence (OR 3.25, 95%CI 2.07-5.09) and starting treatment in prison (OR 1.77, 95%CI 1.04-3.01) were associated with treatment success. Smoking (OR 0.44, 95%CI 0.21-0.92) and bilateral cavitary disease (OR 0.51, 95%CI 0.34-0.77) were associated with worse outcomes. For alcohol users, developing hepatotoxicity was associated with better outcomes (OR 4.40, 95%CI 1.79-10.81) than not (OR 0.42, 95%CI 0.25-0.68). One or more medications were permanently stopped in 10/91 patients, but in no case was treatment entirely discontinued. CONCLUSION: MDR-TB treatment in the face of hepatotoxicity during therapy did not result in a statistically significant increase in poor outcomes.

Expanding global HIV treatment: case studies from the field.

In the last 25 years, human immunodeficiency virus (HIV) has become the leading infectious killer of adults globally, with an estimated 44 million people infected with the virus worldwide. Most of these individuals live in poor regions of the world, particularly sub-Saharan Africa. Although a great deal of work has been done in identifying and treating individuals with the disease, there has been little action to date to address the complex socioeconomic factors that lie at the heart of this global pandemic. Understanding and responding to such factors is of paramount importance if HIV infection is to be managed in a meaningful way. This article explores the social context of people living with HIV in three different geographic and epidemiologic settings and highlights the social factors that shape and define an individual's risk of acquiring HIV. It also discusses unique programs aimed at addressing the complex realities of the world in which HIV thrives. These programs can act as models of HIV prevention and treatment.

Treating multidrug-resistant tuberculosis in Tomsk, Russia: developing programs that address the linkage between poverty and disease.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are diseases of poverty. Because Mycobacterium tuberculosis exists predominantly in a social space often defined by poverty and its comorbidities--overcrowded or congregate living conditions, substance dependence or abuse, and lack of access to proper health services, to name a few--the biology of this organism and of TB drug resistance is intimately linked to the social world in which patients live. This association is demonstrated in Russia, where political changes in the 1990s resulted in increased socioeconomic inequality and a breakdown in health services. The effect on TB and MDR-TB is reflected both in terms of a rise in TB and MDR-TB incidence and increased morbidity and mortality associated with the disease. We present the case example of Tomsk Oblast to delineate how poverty contributed to a growing MDR-TB epidemic and increasing socioeconomic barriers to successful care, even when available. The MDR-TB pilot project implemented in Tomsk addressed both programmatic and socioeconomic factors associated with unfavorable outcomes. The result has been a strengthening of the overall TB control program in the region and improved case-holding for the most vulnerable patients. The model of MDR-TB care in Tomsk is applicable for other resource-poor settings facing challenges to TB and MDR-TB control.

Adverse reactions among patients being treated for MDR-TB in Tomsk, Russia.

BACKGROUND AND SIGNIFICANCE: Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging because of the toxicity of second-line medications. Little is known about whether adverse events impact treatment outcome. METHODS: We conducted a retrospective case series of 244 MDR-TB patients enrolled in Tomsk between 10 September 2000 and 10 September 2002. Adverse reactions were determined by laboratory data and/or clinical criteria. A multiple logistic regression model was performed to determine whether the occurrence of adverse reactions was associated with poor treatment outcome. RESULTS: In this cohort, 76.0% were cured, 6.6% failed, 4.9% died and 11.5% defaulted. Adverse events were observed in 73.3% of patients, occurring in 74.8% of patients who were adherent (taking at least 80% of prescribed doses) and 59.1% of non-adherent individuals (P = 0.11). The impact of adverse events on outcome was modified by non-adherence; among adherent patients, the occurrence of any adverse reaction was associated with treatment cure (adjusted odds ratio 3.24, 95% confidence interval 1.56-6.70). CONCLUSION: Adverse reactions occurred frequently in MDR-TB patients in Tomsk, Russia, but did not negatively impact treatment outcome. The occurrence of adverse reactions among adherent patients was associated with treatment cure.

Improved case detection of active tuberculosis associated with an antiretroviral treatment program in Lesotho.

Tuberculosis (TB) remains the leading infectious killer of adults with human immunodeficiency virus (HIV) globally. Lesotho has the third highest prevalence of HIV and the fourth highest prevalence of TB worldwide, and the majority of TB patients are co-infected with HIV. This paper describes an antiretroviral treatment (ART) program instituted in a health center in a mountain region of Lesotho. Although the main goal of the program was to increase HIV detection and initiate ART for patients, the program also resulted in a ten-fold increase in the detection of TB among patients with and without HIV.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in countries of the former Soviet Union in both the civilian and prison sectors. OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this program between 10 September 2000 and 10 September 2002. The program involves both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome was defined as death, default and treatment failure. RESULTS: Among the 244 patients who received treatment, 77% were cured, 5% died, 7% failed, and 12% defaulted. In a multivariable analysis, alcohol consumption during treatment and the presence of both cavitary and bilateral disease were found to be the strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has resulted in high cure rates and low rates of default. However, alcohol use among patients with MDR-TB is associated with poor treatment outcomes. Better understanding and programmatic alcohol interventions are needed if large-scale treatment of MDR-TB is to be successful in areas with high rates of alcohol use disorders.

Clinical and programmatic considerations in the treatment of MDR-TB in children: a series of 16 patients from Lima, Peru.

SETTING: Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB. OBJECTIVE: To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs. RESULTS: Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy. CONCLUSIONS: Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

Peripheral neuropathy associated with treatment for multidrug-resistant tuberculosis.

OBJECTIVE: To review the incidence and management of peripheral neuropathy in patients receiving therapy for MDR-TB. METHODS: A case series with retrospective chart review of 75 patients who initiated individualized therapy for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru, between 1 August 1996 and 31 January 1999. RESULTS: All patients had confirmed MDR-TB and were receiving individualized therapy, comprised of an average of six drugs. Ten (13%) of these patients presented with symptoms of peripheral neuropathy, confirmed by electromyography. All symptoms were reported in the lower extremities, and all were sensory in nature. Median time to presentation from initiation of MDR-TB therapy was 9.1 months. No significant risk factors associated with development of peripheral neuropathy were identified. Management strategies depended on the severity of symptoms and included the treatment of contributing co-morbidities, medications for neuropathic pain, and adjustment of doses of possible offending agents. All patients responded to management; three patients were left with mild residual symptoms. Patients whose neuropathy resolved had symptoms for a median of 7 months. CONCLUSIONS: Peripheral neuropathy was encountered in 13% of our cohort of MDR-TB patients. The diagnosis of peripheral neuropathy can be based on clinical presentation alone, and effective management of this side-effect is possible without sacrificing MDR-TB treatment efficacy.

Occurrence of serious adverse effects in patients receiving community-based therapy for multidrug-resistant tuberculosis.

SETTING: A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in an urban shantytown of Lima, Peru. OBJECTIVES: To ascertain the occurrence of serious adverse effects associated with therapy for MDR-TB in northern Lima, Peru, where therapy was individualized according to drug-susceptibility testing of patients' infecting strains and delivered through a community-based program. DESIGN: A retrospective record review of 60 patients who had received individualized therapy for MDR-TB between September 1996 and October 1998. RESULTS: Although adverse effects were common, they occurred less frequently than previously reported in the literature and were rarely life-threatening. Effects occurring most frequently in this population included: mild gastritis (100%), dermatological effects (43.3%), peripheral neuropathy (16.7%), depression (18.3%), and anxiety (11.7%). These effects never resulted in the discontinuation of anti-tuberculosis therapy, and only occasionally resulted in the suspension of an agent (11.7%). CONCLUSION: In young patients with little comorbid disease, multidrug, long-course regimens rarely caused life-threatening adverse effects. Common side effects may be managed successfully on an out-patient basis through a community-based treatment program in conjunction with MDR-TB experts, even in resource-poor settings. The very low rate of default in this cohort offers hope that strategies to manage the adverse effects may reduce the incidence of abandonment of therapy and increase rates of cure.

Effect of administering short-course, standardized regimens in individuals infected with drug-resistant Mycobacterium tuberculosis strains.

Presented here are the cases of three siblings with multidrug-resistant tuberculosis who demonstrated increased antituberculous-drug resistance during the periods in which they received standard regimens of directly observed, short-course chemotherapy that were administered before the susceptibility patterns of their Mycobacterium tuberculosis isolates had been checked. More specifically, they acquired resistance to drugs they received as part of ineffective standard treatment and retreatment regimens. Development of antituberculous-drug resistance through inadvertent, inadequate therapy appears to be the most likely explanation for the increased resistance seen in these three patients.

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.

"You have to be your own doctor": sociocultural influences on alternative therapy use among gay men with AIDS in west Hollywood.

This article considers the use of alternative therapies by gay men with AIDS in West Hollywood, California. In all, 89 different alternative therapies for HIV and AIDS treatment were uncovered during the course of the study. In addition to the high number of alternative therapies, a majority of the men in the study (69.2 percent) were currently using some type of alternative treatment. Sociocultural influences on the use of alternative therapies are explored, including AIDS activism. Because most of the men (92 percent) also use Western medicine as well, the interface of these two types of treatments is also explored.