Principles of Management of HIV-TB Co-infection

Introduction

I. Principles of Diagnosis in HIV-TB Co-infection

1. Tuberculin skin test (TST) unreliability: TST often gives false-negative results because the test depends on a competent immune response, which is impaired by HIV.
2. Atypical radiology: Chest X-ray shows less cavitation (cavities form due to immune-mediated tissue destruction; with HIV, the immune response is blunted). Lower-lobe or diffuse infiltrates, lymphadenopathy, and miliary patterns are more common.
3. Higher frequency of extrapulmonary TB: Disseminated TB, lymph node TB, CNS TB, and miliary TB are all more common.
4. Preferred diagnostic tool: Xpert MTB/RIF (CBNAAT) is recommended over conventional sputum microscopy as the initial diagnostic test in HIV-associated TB or suspected MDR-TB, as it simultaneously detects MTB and rifampicin resistance. Sputum culture with drug susceptibility testing (DST) should be performed when possible.
5. Intensified Case Finding (ICF): All PLHIV (persons living with HIV/AIDS) should be screened using an expanded four-symptom algorithm: current cough, weight loss, fever, or night sweats (not just cough alone).

• Park's Textbook of Preventive and Social Medicine
• Harrison's Principles of Internal Medicine, 22E

II. General Principles of Treatment

Key Principle: Treat Both Diseases

• Sustained reduction in HIV viral load
• Immunological reconstitution
• Decrease in AIDS-defining illnesses and mortality

Standard ATT Regimen in HIV-TB Co-infection

• Daily therapy is strongly preferred - intermittent (thrice-weekly or twice-weekly) regimens increase risk of relapse and acquired rifamycin resistance in HIV-infected individuals and should be avoided.
• Continuation phase is extended to 7 months if: cavitation is present on CXR, culture conversion is prolonged (>2 months), or the patient is not on ART.
• CNS TB: Total treatment duration extended to 10 months.
• Harrison's Principles of Internal Medicine, 22E (Table 36-2)
• Fishman's Pulmonary Diseases and Disorders

III. Timing of ART Initiation

• Harrison's Principles of Internal Medicine, 22E
• Park's Textbook of Preventive and Social Medicine

IV. Drug-Drug Interactions: The Central Challenge

1. With Protease Inhibitors (PIs): Rifampicin dramatically reduces plasma levels of most PIs (e.g., lopinavir/ritonavir) by 75-95%, rendering them ineffective. PIs should not be used with rifampicin.
   • Alternative: Use rifabutin (lower CYP450 induction) instead of rifampicin if a PI-based regimen is necessary.
2. With NNRTIs (Non-nucleoside reverse transcriptase inhibitors):
   • Efavirenz (EFV): Preferred NNRTI with rifampicin; rifampicin reduces EFV levels by ~25%, but EFV at standard dose (600 mg OD) is generally acceptable.
   • Nevirapine: Rifampicin reduces nevirapine levels by ~55%; avoid this combination.
3. Preferred ART backbone with rifampicin-based ATT:
   • Efavirenz (EFV) + 2 NRTIs (e.g., tenofovir + lamivudine) is the first-line regimen of choice.
   • Dolutegravir at double dose (50 mg BD) can be used with rifampicin.
4. Overlapping toxicities to monitor:
   • Peripheral neuropathy (isoniazid + stavudine/zidovudine)
   • Hepatotoxicity (rifampicin, isoniazid, pyrazinamide + NVP, PIs)
   • GI intolerance
   • Reduced absorption of TB drugs in HIV-positive patients can lower serum drug concentrations, raising risk of relapse or acquired resistance.

• Fishman's Pulmonary Diseases and Disorders
• Harrison's Principles of Internal Medicine, 22E

V. Immune Reconstitution Inflammatory Syndrome (TB-IRIS)

Two Types:

1. Paradoxical TB-IRIS: Patient already on ATT, then starts ART → pre-existing TB lesions worsen.
2. Unmasking TB-IRIS: Patient has subclinical (undiagnosed) TB, starts ART → TB "unmasks" clinically.

Clinical Features:

• Fever, worsening lymphadenopathy, expanding pulmonary infiltrates, new pleural/pericardial effusions
• Typically appears within 1-8 weeks of ART initiation
• More common in those with CD4 <100/µL and high pre-ART viral load

Management of TB-IRIS:

• Do not stop ATT or ART
• NSAIDs for mild IRIS
• Corticosteroids (prednisolone) for moderate-severe IRIS: reduces morbidity significantly
  • Prophylactic prednisolone at the time of ART initiation in advanced HIV disease decreases risk of IRIS without increasing mortality or serious infections
• Surgical drainage if needed for suppurative lymph nodes
• Fishman's Pulmonary Diseases and Disorders
• Park's Textbook of Preventive and Social Medicine
• Goldman-Cecil Medicine (Table 358-4)

VI. Co-trimoxazole Preventive Therapy (CPT)

• Pneumocystis jirovecii pneumonia (PCP)
• Toxoplasmosis
• Bacterial infections

• Park's Textbook of Preventive and Social Medicine

VII. Isoniazid Preventive Therapy (IPT)

• All PLHIV with latent TB (positive TST/IGRA) should receive INH 300 mg daily for 6-9 months (IPT).
• Combination of IPT + ART reduces TB risk in PLHIV by up to 97% (Park's).
• Rule out active TB before initiating IPT.
• Rifampicin for 4 months is an alternative to 9-month INH for LTBI treatment - equally effective and better tolerated.

VIII. Management of MDR-TB in HIV

• Treatment of HIV-positive MDR-TB follows the same regimen as HIV-negative MDR-TB.
• However, treatment is more difficult and adverse events are far more common.
• Rigorous monitoring for adherence, early detection of adverse events, and minimizing "lost to follow-up" are essential.
• ART must still be given to all HIV-MDR-TB patients irrespective of CD4 count.

IX. The "Three I's" Strategy (WHO Framework)

1. Intensified Case Finding (ICF): Screen all PLHIV for TB at every visit
2. Isoniazid Preventive Therapy (IPT): Give IPT to PLHIV without active TB
3. Infection Control: Implement TB infection control in healthcare and congregate settings

Summary Table

• Harrison's Principles of Internal Medicine, 22E - Treatment of TB in HIV co-infection (p. 1463)
• Fishman's Pulmonary Diseases and Disorders - HIV Co-infection in TB management
• Park's Textbook of Preventive and Social Medicine - Tuberculosis and HIV chapter
• Goldman-Cecil Medicine - IRIS manifestations (Table 358-4)