Introduction And Pathogenesis

The interaction between Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis is termed a syndemic or a fatal combination.
People Living with HIV are approximately 18 times more likely to develop active tuberculosis compared to HIV-negative individuals.
Tuberculosis represents the leading cause of death among HIV-infected children.
Bidirectional Interaction: HIV depletes CD4+ T cells, preventing the formation of solid granulomas to contain the bacilli and increasing hematogenous dissemination. Conversely, active tuberculosis increases HIV viral replication, accelerating CD4 decline and progression to AIDS.

Clinical Manifestations

The clinical presentation depends significantly on the degree of underlying immunosuppression.

Disease Type	Clinical Characteristics
Pulmonary Tuberculosis	In early HIV, signs mimic uninfected children (upper lobe infiltrates, cavitation). In advanced HIV, atypical presentations manifest with lower lobe involvement, diffuse interstitial infiltrates, and miliary patterns with less cavitation. Symptoms like chronic cough, fever, and weight loss overlap with other opportunistic infections like Lymphoid Interstitial Pneumonitis.
Extrapulmonary Tuberculosis	Significantly more common in HIV-infected children. Common sites include peripheral lymph nodes (scrofula), pleura, abdomen, and disseminated miliary disease. Patients exhibit a heightened risk of Tuberculous Meningitis, which carries poor neurological outcomes.

Implement Intensified Case Finding for all children living with HIV using the 4-Symptom Screen: current cough, fever, poor weight gain or weight loss, and history of contact with a tuberculosis case.
The presence of any single symptom mandates a thorough evaluation for active disease.

Modality	Characteristics And Utility
Nucleic Acid Amplification Tests	Cartridge Based Nucleic Acid Amplification Test (GeneXpert) or TrueNat serves as the upfront diagnostic test of choice utilizing sputum, gastric aspirate, or bronchoalveolar lavage. Offers high sensitivity and simultaneously detects Rifampicin resistance.
Smear And Culture	Smear microscopy exhibits poor sensitivity due to the paucibacillary nature of the disease in this cohort. Liquid or solid culture remains the gold standard for drug susceptibility testing.
Immunodiagnosis	Tuberculin Skin Test utilizes a cut-off of $\ge$5 mm induration for positivity. High rates of false negatives (anergy) occur due to profound T-cell depletion. A negative test never rules out tuberculosis.

ATT Regimen: Administer the standard regimen utilizing 2 months of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol, followed by 4 months of Isoniazid and Rifampicin. Daily therapy is strictly mandatory, and Pyridoxine supplementation is required to prevent neuropathy.
ART Initiation: Initiate tuberculosis treatment first. Start ART within 2 weeks to 2 months of starting ATT.
Central Nervous System Exception: For Tuberculous Meningitis, strictly delay ART initiation until 4 to 8 weeks after starting ATT to prevent potentially fatal intracranial Immune Reconstitution Inflammatory Syndrome.

Rifampicin acts as a potent inducer of hepatic CYP450 enzymes, significantly lowering the levels of concurrently administered antiretrovirals.

Antiretroviral Drug	Pharmacological Adjustment Required With Rifampicin
Dolutegravir	Must double the dose to twice daily during tuberculosis treatment and continue for 2 weeks after stopping Rifampicin.
Lopinavir/Ritonavir	Requires super-boosting by changing the Lopinavir to Ritonavir ratio to 1:1.
Nevirapine	Avoid if possible; if utilized, the dose requires an increase by 20-30% bearing a high risk of hepatotoxicity.
Efavirenz	Generally safe; no dose adjustment is typically required.

Features a paradoxical worsening of pre-existing tuberculosis symptoms (Paradoxical IRIS) or unmasking of subclinical infection (Unmasking IRIS) following ART initiation.
Management dictates continuing both ART and ATT while treating severe inflammation with Non-Steroidal Anti-Inflammatory Drugs or Corticosteroids.

Tuberculosis Preventive Therapy (TPT): Isoniazid Preventive Therapy is indicated for all HIV-infected children >12 months without active disease, administered as 6 months of daily Isoniazid or 3 months of weekly Isoniazid plus Rifapentine.
Cotrimoxazole Preventive Therapy: Reduces overall mortality by preventing Pneumocystis pneumonia, malaria, and severe bacterial infections.
BCG Vaccination: Administer strictly at birth to asymptomatic HIV-exposed infants. It remains absolutely contraindicated in symptomatic HIV-infected infants due to the risk of disseminated BCG disease.