ABSTRACT
Otsuka has been engaged in anti-tuberculosis drug development efforts for over 30 years, and is the leading private sector funder of tuberculosis (TB) research and development. Delamanid (DLM), discovered by Otsuka's scientists, has been shown to provide benefit with respect to short-term surrogate markers and long-term treatment outcomes, and it has received regulatory approval for treatment of adult pulmonary multidrug-resistant TB (MDR-TB) as one of only two new anti-tuberculosis drugs in the last 40 years. Lack of drug-drug interactions with major antiretrovirals and efficacy against MDR-TB allow DLM's applicability in a wide range of MDR-TB patients. Current and future efforts are focused on replacing less safe and less efficacious second-line drugs with DLM, its contribution to all-oral and/or shortened treatment regimens, and, ultimately, inclusion in a pan-TB regimen. This manuscript provides a brief review of DLM.
Subject(s)
Antitubercular Agents/therapeutic use , Nitroimidazoles/therapeutic use , Oxazoles/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Clinical Protocols , Clinical Trials, Phase III as Topic , Humans , Randomized Controlled Trials as TopicABSTRACT
Suppression of hepatitis B virus (HBV)-DNA to undetectable levels is an important goal for HIV/HBV-co-infected patients receiving anti-HBV-active antiretroviral therapy (ART), and current guidelines recommend that this outcome should be reached by 1 year of treatment. However, the proportion of patients that fail to achieve an undetectable HBV DNA at this time point and its determinants remain unknown in clinical practice. The objective of this study was to determine the incidence and risk factors for incomplete HBV suppression following 1 year of tenofovir-based ART. We performed a cohort study among tenofovir-treated HIV/HBV-co-infected patients. Patients had HBV viraemia, initiated tenofovir-based ART and had HBV DNA measured at 1 year of therapy. The primary outcome was incomplete HBV suppression (HBV DNA ≥2.6 log IU/mL) at 1 year. Logistic regression determined odds ratio (ORs) of incomplete HBV suppression for risk factors of interest. Among 133 patients, 54% (95% CI, 46-63%) had incomplete HBV suppression at 1 year. Incomplete suppression was associated with higher baseline HBV DNA (OR, 1.46 per log IU/mL increase; 95% CI, 1.1-1.94) and detectable HIV viraemia at 1 year (OR, 2.52; 95% CI, 1.19-5.32). Among 66 patients with suppressed HIV RNA at 1 year, 28 (42%) failed to achieve an undetectable HBV DNA. Failure to suppress HBV DNA by 1 year occurred in a sizeable proportion of tenofovir-treated HIV/HBV-co-infected patients. Higher HBV DNA and detectable HIV viraemia were risk factors for incomplete HBV suppression.
Subject(s)
Anti-HIV Agents/therapeutic use , DNA, Viral/blood , HIV Infections/drug therapy , Hepatitis B virus/physiology , Hepatitis B/drug therapy , Adenine/analogs & derivatives , Adenine/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Cohort Studies , Coinfection , Drug Resistance, Viral , Female , HIV Infections/complications , HIV Infections/virology , Hepatitis B/complications , Hepatitis B/virology , Hepatitis B virus/genetics , Humans , Incidence , Lamivudine/therapeutic use , Male , Middle Aged , Organophosphonates/therapeutic use , Retrospective Studies , Risk Factors , Tenofovir , Viral Load , ViremiaABSTRACT
SETTING: The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. OBJECTIVE: To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. DESIGN: Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). RESULTS: A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). CONCLUSION: We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.
