• Worldwide, the reported prevalence of TB in AIDS patients has ranged from 4% to 44% in different populations.
  
• Compared to non-HIV-infected patients, HIV/TB-infected patients have higher rates of primary disease (37%/6 months vs. 5%/2 years), reactivation disease (7-10% /year vs. 5-8% / lifetime), skin test anergy, and extrapulmonary TB (50%). TB may influence the natural history of HIV by activating macrophages leading to increased HIV expression and rapid progression to AIDS if latent TB is untreated.
  
• Overall, patients with higher CD4 count often present in "classic" fashion whereas those with low CD4 count are more likely to present atypically.

Diagnosis

• Acid Fast Bacilli stain
• Culture
• The sputum smears of ~50% of HIV-infected patients with pulmonary TB are negative by AFB stain, a rate higher than that encountered in HIV negative patients. Bronchoscopy increases the recovery of positive smears and cultures.
• PCR of sputum (50-100% sensitive, 95-100% specific).

HIV-infected patients with pulmonary TB may present with atypical chest x-ray. Lobar infiltrates + hilar adenopathy or diffuse interstitial infiltrate, resembling PCP, may be seen. Chest films are normal in ~10-20% of AIDS-associated pulmonary TB, whereas cavitary disease is much less common, possibly reflecting the overall immune dysfunction of patients with advanced HIV infection.

Prophylaxis

• Chemoprophylaxis of TB, primary or secondary, is currently a controversial issue in the Indian context.
• In the developed world, primary chemoprophylaxis is indicated for all HIV infected individuals with a PPD >5 mm and no active TB. Isoniazid for 6-12 months or rifampicin/pyrizanimide for 2 months can be used for this purpose. The long-term effectiveness of these regimens are not known.
• In India, data regarding incidence of tuberculosis amongst HIV infected individuals and its relation to PPD is lacking.

Treatment

• Initial treatment with 4 drugs (INH 300 mg PO QD, rifampin 600 mg PO QD, ethambutol 15 mg/kg/d, and PZA 25 mg/kg/d) until results of culture and susceptibility are available. In areas where INH resistance rate is > 4%, add streptomycin to the initial treatment regimen until susceptibility results are available.
• If TB isolate is fully susceptible, INH and rifampin should be continued for 9 months, or at least 6 months beyond the last positive culture. However, the optimal length of therapy for HIV-infected TB patients has not been established. It is especially important to assess the clinical and bacteriologic response when treating patients infected with HIV;treatment should be prolonged beyond 6 months if the response is slow or suboptimal.

• Combination preparations may be considered to increase compliance and thus decrease the emergence of resistance.
• Dose schedules depend on the site of infection, but, in general, only meningitis, osteomyelitis, and military TB need prolonged therapy. Treatment of disease at other extrapulmonary sites (lymph nodes, pleura) follows the recommendations for pulmonary TB.
• Chronic suppressive therapy for a patient who has successfully completed a recommended regimen of TB treatment is not necessary.

• Clinical suspicion of MDRTB should be considered when in a proven case of TB the patient is not responding to the WHO retreatment regime and there is reasonable evidence that the patient has been adherent.
• However, diagnosis is entirely laboratory-based where culture and sensitivity patterns may be studied.
• Treatment of MDRTB is complex, since the second-line drugs are less effective, expensive and more toxic. Irrational use of second-line reserve drugs may lead to emergence of incurable TB.
  
  
• Basic principles of rational use of second-line drugs include:

  • In designing a regimen do not aim to keep drugs in reserve. Adding less drugs will further lead to development of resistance to second-line drugs.

  • Prescribe drugs, which the patient has not had previously.

  • If susceptibility test results are not available use at least three new drugs never used and pyrazinamide for 3 months and then two best tolerated drugs for the remaining 18 months (Table 3).

  • If susceptibility test results are available it is easier to devise a regime. However all treatment regimes need to be continued for 18 months.

• P. carinii was originally considered a protozoan, but is now considered to be more closely related to fungi. It is thought that infection is transmitted from human to human or from environmental reservoirs to humans.
• P. carinii most commonly involves the lung and extrapulmonary pneumocystosis is rare. Typically, the patient presents with cough with or without scanty expectoration, breathlessness, chest pain and fever. Usually the tempo of development and progression of these symptoms is sub-acute spanning over a month or more.
• Chest examination is mostly normal. However, diffuse rales may be encountered.
• The chest X-ray may provide a clue to the diagnosis of PCP. Classically, PCP presents with diffuse bilateral, symmetrical reticular or granular opacities (Fig. 1). Except pleural effusions and intrathoracic adenopathy, all radiographic patterns of lung involvement have been described with PCP. These include focal infiltrates, lobar/segmental consolidation, nodular shadows and cavitation.
• Diagnosis of PCP relies on demonstrating the organism in sputum or bronchoalveolar lavage (BAL) specimens. However, most often PCP is associated with dry cough.
• For initial treatment of PCP, Trimethoprim-Sulphamethoxazole (TMP-SMX) is the drug of choice. The dose is 2 DS tablets tid for 21 days.
• After recovery from an initial episode of PCP, life long secondary prophylaxis with TMP-SMX is indicated.

Mycobacterium avium Complex (Mac)

• Frequently found in sputum. Occasionally causes invasive pulmonary disease.
• A late manifestation of AIDS. CD4 is the strongest predictor of disseminated MAC infection and occurs when there is marked immunosuppression.

Clinical Manifestations

• Fever, weight loss, diarrhea, night sweats, chills, abdominal pain, chronic malabsorption, hepatosplenomegaly, diffuse lymphadenopathy and occasionally adrenal insufficiency.

Diagnosis

• Clinical syndrome, blood cultures (lysis-centrifugation), cultures of stool, liver, lymph nodes or bone marrow biopsy. Biopsy specimens reveal poorly formed granulomas and sheets of acid fast organisms. Anemia, abnormal liver functions with increased alkaline phosphatase are common.

Treatment

• Colonization of the lungs or the GI tract with MAC in the absence of bacteremia should not be treated, although such patients may be candidates for prophylaxis. Routine, periodic screening of sputum or stool for MAC colonization is not useful in predicting dissemination, nor do we recommend routine (monthly) surveillance blood cultures.
• A life-long regimen combining clarithromycin 500 mg PO BID with ethambutol 15-20 mg/kg/d + rifabutin 300 mg PO QD is generally effective. Azithromycin can be used in patients who are intolerant of clarithromycin.
• Treatment may be started if patient has typical symptoms of disseminated MAC and should not be delayed pending culture results. Treatment improves symptoms, quality of life and survival in HIV patients.
• There is no benefit from avoiding specific foods or water sources to reduce exposure to MAC.

Prophylaxis

• Preventive therapy against MAC is recommended when the CD4 count is < 50/ml, in patients with no active disease due to MAC, TB, or any other mycobacteria. Assess potential risks/benefits individually. Prophylactic regimens include (in descending order of preference):

1. Azithromycin 1200 mg/wk PO.
2. Clarithromycin 500 mg PO BID
3. Rifabutin 300 mg PO QD

Bacterial Pneumonia

• Bacterial pneumonia is the most common form of pneumonia in HIV patients.
• S. pneumoniae is one of the most frequent invasive bacterial infections in HIV patients.
• Chest x-ray changes are often atypical, resembling PCP in 50% of cases. Sputum Gram stain and cultures obtained by sputum induction or BAL help establish the diagnosis.
• Treatment response to typical antibiotics is usually rapid and the clinical course and prognosis resemble those in normal hosts.
• Other bacterial pathogens that cause pneumonia include Hemophilus, Moraxella, Klebsiella, N. meningitides, Rhodococcus, S. aureus and Nocardia. An indolent, relapsing form of Pseudomonas pneumonia and bacteremia has been described in AIDS patients with low CD4 count.

Non-Infectious Pulmonary Disease

1. Kaposi’s Sarcoma (KS)

• Persistent dry cough, dyspnea, or hemoptysis, usually associated with skin lesions, although, pulmonary KS may occur without skin lesions. Chest x-ray shows patchy nodularity and pleural effusion, and CT scan may show multiple lesions. Bronchoscopy usually reveals endobronchial KS.
• Pulmonary KS can be differentiated from PCP and other pulmonary diseases by the typical chest x-ray changes, a normal gallium scan, and by the findings on bronchoscopy.
• Biopsy of pulmonary KS is usually avoided because of risk of bleeding, though the frequency of this complication is over-estimated. Biopsy is often negative as the lesions are submucosal. KS is rare in absence of endobronchial lesions.
• Treatment:
  Systemic chemotherapy with vincristine, vinblastine, etoposide, bleomycin, paclitaxel, liposomal daunorubicin, or doxorubicin may be helpful. Radiotherapy may provide palliation if patients refuse or are intolerant of chemotherapy.

2. Non-Specific Interstitial Pneumonitis may resemble PCP clinically and radiographically in HIV patients who have normal CD4 count. Biopsy shows interstitial infiltrate of mature lymphocytes, plasma cells and macrophages. The disease is often self-limited, but steroids may help.
3. Lymphoid Interstitial Pneumonitis is frequently encountered in HIV-infected children but is uncommon in adults. Cough and progressive shortness of breath may be associated with parotid enlargement. Chest x-ray shows diffuse interstitial infiltrate. Diagnosis is made by transbronchial or open lung biopsy. Treatment with steroids may be effective.
4. Bullous lung disease and emphysema have been reported in HIV patients. Most patients have previous history of PCP, but some have no prior history of any opportunistic infections. Chest x-ray may show only subtle abnormalities, but CT scan demonstrates bullae, air cysts, and/or vascular destruction. PFTs show minimal airflow obstruction, but there is decreased D2CO.