HIV and LUNG

The lungs are one of the chief target organs for HIV-associated disease, and almost 70% of the patients suffer at least one respiratory complication during the course of their illness.

Bacterial Streptococcus pneumoniae Haemophilus influenzae No organism identified, but responsive to antibacterial therapy Mycobacterial Mycobacteria tuberculosis Fungal Pneumocystis jiroveci

Bacterial Pseudomonas aeruginosa Staphylococcus aureus (especially MRSA) Enterobacteriaceae Legionella spp. Nocardia spp. Rhodococcus equi Mycobacterial Mycobacterium kansasii Mycobacterium avium complex Fungal Cryptococcus neoformans Histoplasma capsulatum Coccidioides immitis Aspergillus spp. Blastomyces dermatitidis

Viral Influenza Cytomegalovirus Herpes simplex virus Adenovirus Respiratory syncytial virus Parainfluenza virus Parasitic Toxoplasma gondii Strongyloides stercoralis Microsporidia spp. Cryptosporidium parvum

Kaposis sarcoma Non-Hodgkins lymphoma Lung cancer Primary pulmonary hypertension Congestive heart failure Lymphocytic (or lymphoid) interstitial pneumonitis Emphysema Abacavir hypersensitivity

CD >400 : Increase risk of Bacterial infection MTB CD4 200-400 : Increase risk Recurrent BI MTB Lymphoma Cardiomyopathy

CD4 <200 : Increase risk of PCP Disseminated MTB CD4 <100 : Increase risk of PCP MTB & NTM CMV Fungal Infections Kaposi's sarcoma Lymphoma

Multiorganism infection usually Streptococcus pneumoniae, Hemophilus influenzae, Pseudomonas and Staphylococcus aureus.
Compared with HIV Negative cases, Bacterial Pneumonia is six to ten times common in HIV positive untreated patients. Bacteremia is 100 times more common in HIV infected persons irrespective of CD4 count.

Patients with bacterial pneumonia typically present with an acute onset of fever and productive cough.
The conventional chest X-ray (CXR) - reported accuracies of diagnosing 64% -----bacterial pneumonia 75%------ PCP 84% -----MTB Sputum for Gram stain Blood Culture

Treatment similar to non-HIV cases Beta Lactum Plus Macrolides preferred Duration is 7 days
Aviod R-flqs Reserved for MDR TB can be used only after ruling out PTB.

P. Jirovecii remains the second most common opportunistic and most common life-threatening pulmonary infection in AIDS
Radiographic changes are varied and may lag behind the symptoms

Nonproductive cough Progressive breathlessness With or without fever

X-ray may be normal in 10% cases

Second or third episode of PJP Advanced age Low hemoglobin Hypoxemia Ptx Co-existent Pulmonary Kaposi sarcoma Medical co-morbidity Requiring ICU or ventilator care

Mild -Pao2> 11.0 kpa or Sao2> 96%

Moderate -Pa02 8.0-11.0 Kpa or Sao2 92-96% Severe -Pao2 <8.0 Kpa or Sao2 <92%

X-ray Sputum for PJP cyst/ Tropozoa BAL for Cyst / Tropozoa Serum LDH ABG

Co-infection with CMV and other pathogens will be detected in more than half of Pneumocystis-infected patients.

Blood absolute CD4 count < 200/ L Blood CD4 count < 14% of total lymphocyte count Unexplained fever for > 3 weeks duration Persistent or recurrent oral/pharyngeal Candida History of another AIDS defining diagnosis e.g Kaposi Sarcoma

TMP-SMX Aerosolized Pentamidine Dapsone Atovaquone Azithromycin

Patients on CART with sustained increase in CD4 count > 200/ L and undetectable plasma HIV RNA for > 3 months.

Tuberculosis is most common opportunistic infection in HIV infected patients in India & worldwide.
Risk factor for reactivation LTBIHIV negative rate <1% per year (10% lifetime) HIV positive rate ~ 7-10% per year (apprx 100% lifetime).

Both the clinical & radiological features of T.B are dependant on the degree of immunosuppression
Typical Presentation vs Atypical Presentation depends on CD4 count

CD 4 Cell count 350 cells/mm3

ART Recommendation Recommend ART

Timing of ART in relation to treatment for Ds TB / MDR TB After 2 weeks, as soon as the treatment for DS TB & MDR TB is tolerated. Re-evaluate patient monthly for consideration of ART. CD4 testing is recommended every 3 months during treatment for MDR TB

> 350 cells/mm3

Defer ART

Not available

Recommend ART

After 2 weeks, as soon as the treatment for DS TB & MDR TB is tolerated.

Irrespective of CD4 cell counts, patients coinfected with HIV and TB should be started on ART as soon as possible after starting TB treatment (within 8 weeks after the start of TB treatment).

Multiple pills
Drug interactions Drug toxicities

IRIS

Use of Rifampicin with PI / NNRTI based ART is contraindicated. NRTI are not metabolized by hepatic cyto. P450 enzyme system hence they can safely be used with Rifampicin based ATT
2NRTI + EFV is recommended as the preferred 1st line.

 first line ATT (SHEZ)

with no interactions with ART and can be used safely : SHEZ x 2 months followed by SHZ x 7months

HIV and MDR/XDR TB: Perfect Storm Poor treatment outcomes and exceptionally high mortality rates
Rapid disease progression Delayed diagnosis Inadequate initial treatment

KwaZulu Natal outbreak: 52 of 53 (HIV + XDR TB) died within median 16 days of diagnosis

Use of CART leads to 50-90% reduction in HIV associated OI (TB) and Malignancies

Lawn SD, et al, Am J Respir Crit Care Med, 2008;177:680-685

ART: Immune Function inflammation in TB lesions Worsening Symp./Signs

11-35% pts on ART C/F: Fever / Adenopathy /Pul infiltrates Serositis

D/D: other OI S/E of drugs T/T failure of TB DR TB C/F of immune reconstitution: within days of ART Median time 11 days Risk factors:Severity of illness (risk with very low CD4) Potency of ART

Rarely requires stopping ATT / CART

Requires NSAID for symptomatic relief For life threatening states : short course steroids may be give to suppress inflammation while ATT and ART are continued

KS is the most common AIDS-related malignancy, male:female ratio is 50:1. KS Herpes virus or Human Herpes virus 8 has been identified as the probable cause

Pulmonary involvement occurs in up to 50% and is almost always preceded by cutaneous or visceral disease.
Hilar Adenopathy- 25%

Pleural Effusion 40%

FOB in > 50% cases multiple flat/raised red, purple endobronchial or endotracheal lesions
Biopsy cautious rarely needed ??

CART Chemotherapy

AIDS-related lymphoma (ARL) is the second most common malignancy. The incidence is increasing, possibly due to the longer life expectancy coupled with the longer latency period required for the development of neoplasms.

Non-Hodgkins Lymphoma (NHL) accounts for 90% and the majority of cases are associated with Epstein-Barr virus.
NHL is typically extranodal and usually disseminated at the time of diagnosis Thoracic involvement is reported in up to 40%.

Pulmonary Mass or coin Lesions

Mediastinal Lymphadenopathy Pleural Effusion

Restoration of immune function with antiretroviral therapy along with chemotherapy improves survival

Lung cancer appears to be two to four times common in HIV infected smokers. Presentation is usually with disseminated disease and prognosis is poor.

Despite the development of effective CART and better prophylaxis of OIs, pulmonary complications remains an important cause of morbidity and mortality.
High index of suspicion and timely therapy will prolong survival.

Thank you!