Abstract
The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB.
Highlights
The global epidemics of HIV/AIDS and tuberculosis (TB) both remain huge challenges to international public health, causing illness and death in millions of people worldwide each year (Table 1) [1]
The global co-epidemic has been further compounded in recent years by the emergence of the growing challenge of multi-drug resistant TB (MDR-TB) [5,6]
The World Health Organization (WHO) DOTS TB control strategy used in isolation provides far from optimum case
Summary
The global epidemics of HIV/AIDS and tuberculosis (TB) both remain huge challenges to international public health, causing illness and death in millions of people worldwide each year (Table 1) [1]. Both observational and randomized controlled trials conducted in sub-Saharan Africa have shown that this simple intervention is associated with a substantial reduction in mortality among patients with HIV-associated TB (range, 19% to 46%) [40,41,42,43,44] (Table 4) This beneficial effect was observed in a range of settings with high or low rates of bacterial resistance to the drug and is additive in reducing early mortality when combined with ART [45]. Adequate plasma concentrations of lopinavir are achieved in adults by doubling the dose of lopinavir/ritonavir in the tablet formulation (to 800/200 mg twice daily); this is the simplest approach, especially in settings where the separate ritonavir is not available [71] These approaches are associated with high rates of hepatotoxicity in studies of healthy volunteers, these seem to be much safer in HIV infected patients [71,72,73,74,75,76]. TB treatment is associated with a spectrum of cutaneous adverse reactions including morbiliform rashes,
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