1. HIV & TB

2. Worldwide TB is the most important opportunistic infection in HIV patients – its the commonest killer. Around 20 million people worldwide are co infected with HIV and TB. Dual infection of HIV and TB is very low in Australia (sub Saharan Africa > 70%). < 5% of AIDS patients in Australia develop active TB. 1-7% of the HIV infected people with latent TB, will go on to develop active TB each year – a risk that is 4-25x higher than in non-HIV patients. TB affects the course of HIV infection: in vitro cytokines released because of Mycoplasma TB enhances HIV replication. HIV patients newly infected with Mycoplasma TB are more likely to develop symptomatic primary infection.

3. Clinical manifestation depends on: – CD4 status (level of immunosuppresion) – Whether the TB is from recently acquired TB or from a reactivation of latent TB. HIV patients with preserved CD4 counts usually present with pulmonary TB. Atypical manifestations, extra pulmonary or disseminated TB are more common in: – HIV patients with primary TB – Those with reactivated TB – Impaired immunity ( * CD4 count < 200 per microlitre) CharacteristicLate HIV infection * Early HIV infection Pulmonary : extra pulmonary disease 50:5080:20 Clinical presentationOften resembles primary TB Often resembles post-primary TB Chest radiograph Intrathoracic lymphadenopathy CommonRare Lower lobe involvement CommonRare CavitationRareCommon Tuberculin responseRareCommon Sputum smear positivity Less commonCommon Adverse drug reactions CommonRare Relapse after treatment CommonRare

4. Tuberculin skin test should be part of the routine tests of every newly diagnosed HIV infection – test for latent TB. Also all newly diagnosed patients with TB should be asked for HIV risk factors, and tested for HIV. A Mantoux rxn of > 5mm is considered to indicated TB infection in people with HIV. Occasionally patients with pulmonary TB can have normal CXR - unusual. Diagnosis can be tricky particularly in advanced HIV: – Frequently negative sputum smear findings – Atypical radiographic findings – Higher prevalence of extra-pulmonary TB at inaccessible sites – Resemblance to other opportunistic pulmonary infections Mycobacterium culture is most useful in Dx in such cases

5. Rx of TB in HIV patients is complicated – only managed by expert doctors. Rifampicin has pharmacokinetic interactions with protease inhibitors (PI) – via hepatic cytochrome p450. There are also overlapping toxicities between HAART and anti-TB drugs: in particular hepatotoxicity, peripheral neuropathy and GI side effects. In HIV patients not on HAART, standard TB therapy is good. With those on HAART: – Rifabutin is used instead of rifampicin. – Or rifampicin could be used with efavirenz, or with ritonavir plus saquinavir. – Isonazid, ethambutol and pyrazinamide are used in standard doses. MDR occurs in about 6% of cases of TB in HIV patients (2 nd line Rx – aminoglycosides or quinolones). Paradoxical treatment rxn – patients who begin HAART and anti-TB drugs at same times can develop fever, lymph gland enlargment or pulmonary infiltration week later – due to heightened immune response to mycoplasma TB secondary to HAART therapy.