TB and HIV A Deadly Combination
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
TB and HIV • 14% of all TB cases in adults are attributable to HIV infection • Up to 500,000 die each year from HIV associated TB • ~80% of co-infections are found in Africa
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Diagnosis of TB in the Face of HIV Infection • Presentation and radiologic features often atypical • More likely to have a normal CXR • More likely to be smear negative but culture positive • Using liquid media cultures often posive within 7-28 days Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Clinical Presentation • Reactivation of latent disease is common especially with low CD4 counts • Primary infection may be at different site to reactivation site • Reactivation can develop years after primary infection • Progression may be rapid Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Diagnosis of TB in the Face of HIV Infection: • Culture and sensitivity remains Gold Standard • Liquid based culture systems preferable • Tuberculin Skin Tests • Can Identify latent infection • Sensitivity low in patients with low CD4 counts • Prior BCG vaccination may give false positive result
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Diagnosis of TB in the Face of HIV Infection: • Interferon Tests • May not perform well at very low CD4 counts but probably better than Tuberculin Skin Tests • Detect latent infection • Not affected by BCG • Not affected by previous infection with atypical TB, with exception of M kansasii
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Diagnosis of TB in the Face of HIV Infection: • Molecular Methods • Sensitivity and specificity of NAATs highly variable • Molecular probes for Rifampicin resistance are useful. 90%+ of isolates that are Rifampicin resistant are INH resistant
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Treatment of TB in Face of HIV Infection • 2 Phase Approach • Initial phase for 2 months INH, Rifampicin, Pyrazinamide, Ethambutol. • Continuation Phase for minimum of 4 months INH and Rifampicin • If MAI suspected Azithromycin or Clarithromycin is added to above regimens
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Treatment of TB in Face of HIV Infection • Prolonged Duration of Treatment: • Continuation phase prolonged in cavitating disease where patient remains culture positive at 2/12 • Where Pyrazinamide is not used in Initial phase • CNS disease
• Optimal duration of treatment in co-infected patients not defined Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Treatment Interruptions • Common due to poor adherence and side effects • Can resume treatment with no added doses if interruption <14 days in initial phase or <3 months in continuation phase • Can continue unless ALT or other transaminase >x3 ULN
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Treatment • Initiation of ART should not be delayed if possible. • Better outcome if started early • Toxicities may prevent early initiation and are common • May see worsening of symptoms (IRIS) with very early initiation Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Drug-Drug Interactions • NNRTIs and PIs metabolized via CYP3A4 • Rifa drugs induce CYP3A4 Rifampicin>Rifabutin • Absorption and distribution of PIs mediated through PgP an intestinal drug transporter • Activity of PgP increased by Rifampicin • Rifabutin metabolized via CYP A4 but not Rifampicin Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Drug –Drug Interactions • PIs may inhibit CYP3A4 • Efavfirenz induces CYP3A4 • Interactions are complex
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Drug Interactions â&#x20AC;˘ Rifampicin and Nevirapine both relatively inexpensive therefore use in resource poor countries is an attractive option But â&#x20AC;˘ Both hepatotoxic, therefore should not be used concomitantly
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital
Drug Interactions: Potential solutions • Rifabutin commonly used in 3 days a week regimen in combination with PI • Dose adjustment of Efavirenz when Rifa drug used • Aminoglycosides eg Amikacin can be used but long term toxicity common and monitoring required
Dr D Rowen. Dept GU/HIV Medicine Royal South Hants Hospital