Diagnostic Markers and Treatment for HIV and Tuberculosis
HIV Diagnostic Markers
For HIV diagnosis, use the ELISA as the primary screening test followed by Western blot confirmation for any repeatedly reactive ELISA results. 1
Primary Diagnostic Approach
- ELISA (Enzyme-Linked Immunosorbent Assay) is the initial screening test for anti-HIV-1 antibodies, offering both high sensitivity and specificity at low cost 1
- Western blot serves as the confirmatory test following a repeatedly reactive ELISA, with false-positive results being extremely rare 1
- Rapid diagnostic tests (RDTs) are available but perform poorly compared to ELISA, with sensitivity of only 77.5% and should have reactive results confirmed by Western blot 2
Alternative Testing Methods
- Oral mucosal transudate and urine testing provide noninvasive options 1
- Rapid and home sample collection kits offer easier access to testing 1
Critical Caveat
Test results inconsistent with clinical or laboratory findings should be questioned, repeated, or supplemented, as false-positives can occur 1
Tuberculosis Diagnostic Markers
Collect at least three sputum specimens (including one early morning specimen) for acid-fast bacilli (AFB) smear microscopy and culture, and perform Xpert MTB/RIF molecular testing on at least one specimen. 3
Core Diagnostic Tests
- Sputum AFB smear microscopy and culture on at least three specimens, with at least one early morning sample 3
- Xpert MTB/RIF (or Xpert Ultra) rapid molecular test on at least one specimen to confirm TB and detect drug resistance 3, 4
- Mycobacterial culture in both liquid and solid media to confirm diagnosis, identify species, and allow comprehensive drug susceptibility testing 3
- Drug susceptibility testing (DST) for isoniazid, rifampin, and ethambutol on all initial positive cultures 5, 3
- Chest X-ray to assess disease extent, identify cavitation, and establish baseline for monitoring 3
Additional Evaluations
- HIV testing should be offered to all TB patients within 2 months of diagnosis due to high co-infection rates 5
- Baseline laboratory tests including complete blood count, liver function tests, and kidney function tests before initiating treatment 3
- Urine lipoarabinomannan (LAM) testing may be helpful in HIV-positive patients with disseminated disease 6, 7
Special Diagnostic Considerations
- Tuberculin skin test (TST) with purified protein derivative (PPD): ≥5 mm induration is positive in HIV-infected persons 5, 6
- TST should be performed as soon as possible after HIV diagnosis, as reliability diminishes with declining CD4+ counts 5
- A negative AFB smear does not exclude TB—approximately 30% of culture-confirmed cases have negative smears 3
- For patients unable to produce sputum, attempt sputum induction before bronchoscopy 3
Treatment Regimens for Tuberculosis
Initiate a four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months. 5, 8, 9
Standard TB Treatment (HIV-Negative Patients)
Initial Phase (2 months)
- Isoniazid 5 mg/kg (max 300 mg) daily 5
- Rifampin 10 mg/kg (max 600 mg) daily 5
- Pyrazinamide 15-30 mg/kg daily 5
- Ethambutol 15-20 mg/kg daily 5
Continuation Phase (4 months)
Critical Treatment Modifications
Patients with cavitation on chest X-ray AND positive cultures at 2 months require a 7-month continuation phase (total 9 months of treatment). 5
Directly Observed Therapy (DOT)
- All TB treatment should be given by directly observed therapy when operationally feasible 5, 8
- When using DOT, drugs may be given 5 days per week with doses adjusted accordingly 5
Treatment for HIV-TB Co-infection
For HIV-infected patients with TB, initiate the same four-drug TB regimen first, then start antiretroviral therapy within 2-8 weeks based on CD4 count. 5, 8, 10
TB Treatment Regimen for HIV Co-infection
- Initial phase: Isoniazid, rifabutin (preferred over rifampin), pyrazinamide, and ethambutol for 2 months 10
- Continuation phase: Isoniazid and rifabutin for 4 months 10
- Rifabutin is preferred over rifampin due to fewer drug interactions with antiretroviral medications, particularly protease inhibitors 10, 6
Timing of Antiretroviral Therapy
- CD4 count <50 cells/mm³: Start ART within 2 weeks of TB treatment 10, 6
- CD4 count >50 cells/mm³: Start ART within 8 weeks of TB treatment 10, 6
Critical Restrictions for HIV-Infected Patients
- Never use once-weekly isoniazid-rifapentine continuation regimens (Regimens 1c and 2b) in HIV-infected patients due to unacceptably high relapse rates with rifamycin resistance 5
- Patients with CD4 counts <100 cells/mm³ should receive daily or three-times-weekly treatment, not twice-weekly regimens, due to risk of acquired rifampin resistance 5
Drug Interaction Management
- Rifampin interacts significantly with protease inhibitors and non-nucleoside reverse transcriptase inhibitors 5, 8
- Rifabutin 150 mg daily can be substituted for rifampin in patients requiring ritonavir or cobicistat-containing ART 6
- Doses of rifabutin and antiretroviral agents may require adjustment 5
Essential Supplementation
- Pyridoxine (vitamin B6) 25-50 mg daily should be given to all HIV-infected patients receiving isoniazid to reduce peripheral neuropathy risk 10, 6
Special Populations
Pregnant Women with HIV-TB Co-infection
- Use isoniazid, rifampin, pyrazinamide, and ethambutol 5
- Pyrazinamide benefits outweigh risks in HIV-infected pregnant women despite inadequate teratogenicity data 5
- Never use aminoglycosides (streptomycin, kanamycin, amikacin) or capreomycin due to fetal ototoxicity 5
Children with HIV-TB Co-infection
- Use the same four-drug regimen as adults 5
- Include ethambutol at 15 mg/kg even in young children who cannot be monitored for visual acuity, unless the strain is known to be susceptible to isoniazid and rifampin 5
- Isoniazid: 10-15 mg/kg daily (max 300 mg) 5
- Rifampin: 10-20 mg/kg daily (max 600 mg) 5
Extrapulmonary TB in HIV-Infected Patients
- Use the same 6-month regimen as for pulmonary TB 5
- TB meningitis, bone/joint TB require at least 9 months of rifamycin-based therapy 5
- Corticosteroids (prednisone 1-2 mg/kg/day for 1-2 weeks, then taper) may be used for severe paradoxical reactions, though evidence is limited 5
Monitoring and Follow-up
During Treatment
- Sputum microscopy and culture at 2 months to assess treatment response 5, 3
- Liver function tests monitored regularly due to increased hepatotoxicity risk in HIV-infected patients 10
- CD4 counts and HIV viral load at least every 3 months 10
- Drug-induced hepatitis defined as AST >3× upper limit of normal with symptoms, or >5× without symptoms 5
Management of Drug-Induced Hepatitis
If hepatitis occurs, immediately stop isoniazid, rifampin, and pyrazinamide 5
- Use two or more non-hepatotoxic drugs (ethambutol, streptomycin, amikacin/kanamycin, capreomycin, or fluoroquinolone) until cause identified 5
- Test for hepatitis A, B, and C viruses 5
- Restart first-line medications sequentially once AST <2× upper limit of normal and symptoms improved 5
Critical Pitfalls to Avoid
- Never add a single drug to a failing regimen—this leads to further drug resistance 8
- Never rely on negative AFB smears alone to exclude TB diagnosis 3
- Never use anergy testing as routine TB screening in HIV-infected persons—it is not useful for clinical decisions 5
- Never delay TB treatment while awaiting culture results in seriously ill patients 5
- Immune reconstitution inflammatory syndrome (IRIS) may occur after ART initiation, presenting as apparent worsening of TB symptoms—rule out treatment failure before diagnosing IRIS 5, 8, 6
- HIV-infected patients may present with atypical TB manifestations, including higher rates of extrapulmonary and disseminated disease with less cavitation 8, 6