Drug-Resistant TB in HIV-Negative and HIV-Positive Patients
Drug-Resistant TB in HIV-Negative and HIV-Positive Patients
Background: Tuberculosis is a leading cause of morbidity and mortality worldwide. Patients with extensively drug-resistant tuberculosis (XDR-TB) have had high mortality rates, especially when coinfected with HIV.
Methods: A retrospective cohort study of the first 206 patients treated for XDR-TB in Eastern Cape Province, South Africa, October 2006 to January 2008, a province that has treated multidrug-resistant tuberculosis since 2000. All 206 patients were hospitalized for treatment until monthly sputum specimens were culture negative.
Results: Sixty-five patients diagnosed with XDR-TB died before XDR-TB treatment start. Among 195 patients starting treatment with a known HIV status, 108 (55.4%) were HIV positive, and 86 patients (44.1%) died during the first year of treatment. HIV-positive patients receiving antiretroviral treatment (ARVs) fared and HIV-negative patients, and more of both these groups survived than HIV-positive patients not on ARVs. However, HIV-negative patients experienced more serious adverse events requiring the withdrawal of medications than did HIV-positive patients, regardless of the use of ARVs.
Conclusions: Experience in Eastern Cape Province, South Africa, suggests that patients can be treated for both XDR-TB and HIV. We have also shown that such combination therapy can be well tolerated by patients.
Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Multidrug-resistant TB (MDR-TB) is an increasing threat, causing an estimated 489 000 cases worldwide in 2006. MDR-TB is defined as TB that is resistant to at least the 2 most important first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF). Treatment for MDR-TB is less effective, more toxic, and more costly than is treatment for drug-sensitive TB, requiring the use of less active second-line drugs (SLDs). Extensively drug-resistant (XDR) TB is additionally resistant to the 2 most important SLDs, a fluoroquinolone and any injectable SLD [amikacin (AMK), capreomycin (CAP), or kanamycin]. Since first described in 2005, XDR-TB has been diagnosed in 49 countries and accounts for an estimated 4.9% of MDR-TB cases.
Drug-resistant TB and HIV coinfection were described as a "perfect storm" of illness. The first outbreak of XDR-TB to gain public attention was in KwaZulu-Natal Province (KZN), South Africa, where all XDR-TB patients tested for HIV were positive and 52 of 53 cases died rapidly after diagnosis. Other reports have confirmed high overall mortality in XDR-TB patients, with significantly worse outcomes for HIV-positive-patients.
In 2006, Eastern Cape Province, located south and west of KZN, had a TB incidence of 705 of 100,000. In 2008, it had the single highest MDR-TB caseload in South Africa, however, second-line drug susceptibility testing (SLDST) to diagnose XDR-TB was not available until late 2006. Medications, outside of those used in the standardized treatment of MDR-TB, were also not available. Eastern Cape Province began treatment in October 2006 using a combination of drugs known to be effective against TB, both first-line drugs used in the treatment of MDR-TB [ethambutol (EMB), pyrazinamide (PZA)] and SLDs that were reintroduced to the province [para-amino salicylic acid (PAS), CAP]. In this study, we present the first province-wide follow-up of consecutive patients treated for XDR-TB in South Africa, so as to examine the effect of HIV infection on 12-month survival, and the possible effectiveness of treatment.
Abstract and Introduction
Abstract
Background: Tuberculosis is a leading cause of morbidity and mortality worldwide. Patients with extensively drug-resistant tuberculosis (XDR-TB) have had high mortality rates, especially when coinfected with HIV.
Methods: A retrospective cohort study of the first 206 patients treated for XDR-TB in Eastern Cape Province, South Africa, October 2006 to January 2008, a province that has treated multidrug-resistant tuberculosis since 2000. All 206 patients were hospitalized for treatment until monthly sputum specimens were culture negative.
Results: Sixty-five patients diagnosed with XDR-TB died before XDR-TB treatment start. Among 195 patients starting treatment with a known HIV status, 108 (55.4%) were HIV positive, and 86 patients (44.1%) died during the first year of treatment. HIV-positive patients receiving antiretroviral treatment (ARVs) fared and HIV-negative patients, and more of both these groups survived than HIV-positive patients not on ARVs. However, HIV-negative patients experienced more serious adverse events requiring the withdrawal of medications than did HIV-positive patients, regardless of the use of ARVs.
Conclusions: Experience in Eastern Cape Province, South Africa, suggests that patients can be treated for both XDR-TB and HIV. We have also shown that such combination therapy can be well tolerated by patients.
Introduction
Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Multidrug-resistant TB (MDR-TB) is an increasing threat, causing an estimated 489 000 cases worldwide in 2006. MDR-TB is defined as TB that is resistant to at least the 2 most important first-line anti-TB drugs, isoniazid (INH) and rifampicin (RIF). Treatment for MDR-TB is less effective, more toxic, and more costly than is treatment for drug-sensitive TB, requiring the use of less active second-line drugs (SLDs). Extensively drug-resistant (XDR) TB is additionally resistant to the 2 most important SLDs, a fluoroquinolone and any injectable SLD [amikacin (AMK), capreomycin (CAP), or kanamycin]. Since first described in 2005, XDR-TB has been diagnosed in 49 countries and accounts for an estimated 4.9% of MDR-TB cases.
Drug-resistant TB and HIV coinfection were described as a "perfect storm" of illness. The first outbreak of XDR-TB to gain public attention was in KwaZulu-Natal Province (KZN), South Africa, where all XDR-TB patients tested for HIV were positive and 52 of 53 cases died rapidly after diagnosis. Other reports have confirmed high overall mortality in XDR-TB patients, with significantly worse outcomes for HIV-positive-patients.
In 2006, Eastern Cape Province, located south and west of KZN, had a TB incidence of 705 of 100,000. In 2008, it had the single highest MDR-TB caseload in South Africa, however, second-line drug susceptibility testing (SLDST) to diagnose XDR-TB was not available until late 2006. Medications, outside of those used in the standardized treatment of MDR-TB, were also not available. Eastern Cape Province began treatment in October 2006 using a combination of drugs known to be effective against TB, both first-line drugs used in the treatment of MDR-TB [ethambutol (EMB), pyrazinamide (PZA)] and SLDs that were reintroduced to the province [para-amino salicylic acid (PAS), CAP]. In this study, we present the first province-wide follow-up of consecutive patients treated for XDR-TB in South Africa, so as to examine the effect of HIV infection on 12-month survival, and the possible effectiveness of treatment.
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