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E. Jane Carter, MD Associate Professor of Medicine Alpert School of Medicine at Brown University TB HIV Technical Consultant- AMPATH Partnership Eldoret, kenya
Outline of talk
Basic terminology and pathophysiology Epidemiology of TB and HIV Why entertwined? Challenges of two diseases? Question and (Maybe) Answers
TB Transmission
Tuberculosis is spread through the air Index case must have the pulmonary form of the disease
Tb can cause disease anywhere in the body but only the pulmonary ( lung ) form is contagious to others
Stages of Tuberculosis
Exposure Infection Disease Contagion Not every exposure results in infection Asymptomatic state of being a germ carrier 1/10 carriers will develop disease Only pulmonary cases are contagious to others
Tuberculosis Treatment
TB infection can be cured by treatment with a single drug
IPT = isoniazid preventive therapy Length of therapy is long ( 9-36 months)
Global Burden
TB World Incidence
10
12
14
16
0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002
2003
2004 2005 2006 2007
Burden of TB
9.4 million new cases of TB disease per year
1.1 million cases of co-infection
2 million deaths
380,000 in PLWHA
1 infection per second Leading cause of death in PLWHA Leading cause of death in women of child bearing years globally
Contagion
TB HIV interactions
People who are infected with both HIV and latent TB have a much higher risk of developing active TB
Annual risk of developing active TB of 5-10% Lifetime risk of 50%
Clinical Concern
TB progresses faster in HIV-infected patients
More rapidly moves from infection to disease More rapidly develops severe forms of disease
The rate of progression is determined by the immunosuppression of the HIV patient TB is the earliest OI to occur in HIV, appearing at an increased rate even when the CD 4 count is still relatively preserved TB in HIV-infected patients is more likely to be fatal if undiagnosed or left untreated
Clinical Concerns
TB is harder to diagnose in HIV-infected patients
Patients become ill with lower organism burdens PLWA have increased extrapulmnary disease Diagnostic challenges
Contagious pulmonary cases are diagnosed by smear microscopy Early disease may not be diagnosed by microscopy and require culture Disease outside of the chest usually requires culture diagnosis
TB World Incidence
END result
Autopsies show undiagnosed TB caused death in 14-54% of PLHIV
TB fuels HIV
TB increases HIV load and hetergeneity, locally and systemically Increases cytokines linked to HIV activation Decreases cytokines that suppress HIV growth Studies have varied on the clinical outcomes of TB on HIV
Adverse survival has been shown for TB/HIV patients versus HIV alone HIV progression was not any faster when compared to other AIDS defining conditions (KS,PCP, esoph, candidiasis) TB occurs at all levels of CD4 depression
Treatment concerns
TB treatment involves for drugs HIV treatment involves 3 drugs Usually patients are on CPT as well to prevent other OIs Translates into a minimum of 8 drugs
Adherence Drug Interactions and Side Effects
Treatment of TB Disease
In order to effect a cure, TB must be treated with at least two drugs to which the organism is susceptible.
Two drugs the uncoupling of drugs leads to drug resistance
Treatment concerns
Because the treatment combinations are complex Questions were always should one treatment precede the other? TB treatment could never be delayed due to risk of death but when?
Mortality lower in all cd4 stratifications Adverse events in groups were not different
Timing of therapy
IN HIV ARV timing of ARV initiation was timed to level of immunosuppression 2009 WHO recommended ART for all TB patients but when is best time to start? NEJM Series of articles last week
For those with CD4 count < 50 immediate ART is beneficial in preventing death and further OIs
TB World Incidence
TB Drug resistance
Occurs by means of a genetic mutation The genetic mutations occurs spontaneously and randomly in the environment These mutations occur at know rates for each of the drugs The mutations are independent of each other
Therapeutic implications
Length of treatment Pansusceptible 6 months # of drugs Cure rate
99%
INH resistance
12 months
95%
18 months
2 (H/E)
95%
18-24 months
70%
70%
Enhanced Surveillance
Group 1 = per South Africa guidelines Group 2 =consecutive patients on TB ward Group 3 = consecutive TB suspects (9 months)
C. To decrease the burden of HIV in TB patients C.1. HIV testing and counselling C.2. HIV preventive methods C.3. Cotrimoxazole preventive therapy C.4. HIV/AIDS care and support C.5. Antiretroviral therapy to TB patients.
Questions?
Maybe there will be answers, maybe not yet..