HIV infection and pulmonary disease

1. HIV infection and pulmonary disease

3. Outline • HIV infection and Bacterial pulmonary infection • HIV infection and Pneumocystic carinii pneumonia • HIV infection and Tuberculosis

4. AIDS and bacterial pulmonary infection

5. Major causes of bacterial pneumonia in HIV infected patients Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are the most commonly isolated bacteria, with S. pneumoniae accounting for the majority of cases in which a bacterial pathogen is isolated.~ Bacterial pneumonia in patients with the acquired immunodeficiency syndrome. Polsky B; Gold JW; Whimbey E; et al. Ann Intern Med 1986 Jan;104(1):38-41. ~ Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. Rimland D; Navin TR; Lennox JL; et al. AIDS 2002 Jan 4;16(1):85-95.

6. Factors associated with Pseudomonas pneumonia include prior hospitalization, antibiotic exposure, neutropenia, and advanced immunosuppression. ~ Pulmonary complications of HIV infection: autopsy findings. Afessa B; Green W; Chiao J; Frederick W. Chest 1998 May;113(5):1225-9. ~ Incidence and determinants of Pseudomonas aeruginosa infection among persons with HIV: association with hospital exposure. Sorvillo F; Beall G; Turner PA; Beer VL; Kovacs AA; Kerndt PR. Am J Infect Control 2001 Apr;29(2):79-84. ~ • Pseudomonal infection in AIDS patients is associated with a 33 percent in-hospital mortality rate, poor one-year survival rates, and relapse of infection. ~ Serious Pseudomonas aeruginosa infections in patients infected with human immunodeficiency virus: a case-control study. Fichtenbaum CJ; Woeltje KF; Powderly WG. Clin Infect Dis 1994 Sep;19(3):417-22. ~ Pseudomonas aeruginosa bacteremia in patients infected with human immunodeficiency virus type 1. Vidal F; Mensa J; Martinez JA; et al. Eur J Clin Microbiol Infect Dis 1999 Jul;18(7):473-7.

7. Pathophysiologic mechanisms underlie the susceptibility to infection with encapsulated, pyogenic organisms • Deficiencies in humoral immunity, including HIV–related B lymphocyte dysfunction with impaired antibody responses to S. pneumoniae and P. aeruginosa, and depressed IgA and IgG2 subclass antibody levels. • Decreased serum opsonic activity against pneumococcal capsular polysaccharides • Alveolar macrophage and neutrophil dysfunction.

8. Smoking, which is associated with a five-fold increase in the risk of invasive pneumococcal disease in HIV-infected individuals, remains an important, modifiable risk factor in the HAART era. ~ Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Grau I; Pallares R; Tubau F; et al. Arch Intern Med 2005 Jul 11;165(13):1533-40. • HIV-infected smokers experience decreases in the percentage and absolute numbers of pulmonary CD4+ lymphocytes and suppression of IL-1 beta and TNF-alpha production within the lung, which may contribute to risk of infection.

9. Nosocomial pneumonia in HIV–infected patients is most commonly caused by S. aureus and gram-negative organisms, including P. aeruginosa, K. pneumoniae, and Enterobacter species. • These infections almost always occur late in the course of HIV infection and in patients with additional host factors predisposing to bacterial infections, such as neutropenia. ~ Murray, JF, Felton, CP, Garay, SM, et al. Pulmonary complications of the acquired immunodeficiency syndrome. Report of a National Heart, Lung, and Blood Institute workshop. N Engl J Med 1984; 310:1682. ~ Bacterial infections in adult patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Witt DJ; Craven DE; McCabe WR Am J Med 1987 May;82(5):900-6.

10. Clinical symptoms • The clinical presentation of bacterial pneumonia in the HIV (+) patient is similar to that in patients not infected with HIV. • Most patients have an abrupt onset of fever, chills, cough with sputum production, dyspnea, and pleuritic chest pain. • Leukocytosis (+), excepts severe immunosuppression.

11. Bacteremia is frequently associated with pneumonia, with rates as high as 75 % reported with S. pneumoniae infection. • Pretreatment blood cultures yielded positive results for a probable pathogen in 5%–14% in large series of nonselected patients hospitalized with CAP. ~from ATS CAP guideline 2007

12. Radiologic findings • The most common chest roentgenographic manifestation of bacterial pneumonia in the HIV–infected patient is segmental or lobar consolidation, although diffuse reticulonodular infiltrates and patchy lobar infiltrates may also be seen.

14. Pneumococcal pneumonia (left 2) Staphylococcal pneumonia (up) H.Influenza pneumonia (R’t up) K.P pneumonia (Right lower)

15. Diagnosis • Sputum culture • Blood culture • S. pneumonia can be isolated in blood cultures in up to 60 percent of HIV-infected patients with pneumococcal pneumonia. ~Janoff, EN, Breiman, RF, Daley, CL, Hopewell, PC. Pneumococcal disease during HIV infection: Epidemiologic, clinical. and immunologic perspectives. Ann Intern Med 1992; 117:314.

16. Treatment • Outpatients • Inpatients • -- General ward admissions • -- ICU admissions

19. Prevention • Pneumococcal vaccine • H. influenzae vaccine • -- HIB vaccine is not recommended for adults infected with HIV • Prophylactic antibiotics • -- Trimethoprim–sulfamethoxazole has been shown to decrease the risk for bacterial infections.

20. HIV infection and Pneumocystis carinii infection

21. Pneumocystis jiroveci (formally carinii) pneumonia (PCP), is the most common opportunistic respiratory infection in patients infected with HIV. ~ Pneumocystis pneumonia. Thomas CF Jr; Limper AH N Engl J Med 2004 Jun 10;350(24):2487-98. • PCP remained the leading cause of death, which was associated with not receiving or failing to comply with HAART or PCP prophylaxis. ~Pulvirenti, J, Herrera, P, Venkataraman, P, Ahmed, N. Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era. AIDS Patient Care STDS 2003; 17:261.

22. Epidemiology • Transmission (?) • Incidence • -- 95% of patients who developed PCP had a CD4 count below 200 cells/mm3. ~Stansell, JD, Osmond, DH, Charlebois, E, et al. Predictors of pneumocystis carinii pneumonia in HIV-infected persons. Am J Respir Crit Care Med 1997; 155:60. • -- HIV transmission category, age, smoking history, and use of antiretroviral therapy did not predict development of PCP.

23. Clinical manifestations: • In HIV-infected patients, PCP is generally gradual in onset and characterized by fever (79 to 100 %), cough (95 %), and progressive dyspnea (95 %).

24. Radiologic findings • The most common radiographic abnormalities are diffuse, bilateral interstitial or alveolar infiltrates. • HRCT: patchy or nodular ground-glass attenuation was used to indicate possible PCP.

26. Other lab studies: • Gallium-67 citrate scanning: high sensitivity but low specificity, high cost, delay diagnosis • Diffusing capacity for carbon monoxide (DLCO) • Assessment of oxygenation at rest and with exercise • CD4: <200 cells/mm3 • LDH: the mean LDH of PCP survivors was 340 IU, while the mean level of non-survivors was 447 IU.

27. Diagnosis of PCP infection • Sputum: sensivity: 55-92%; specificity: ~100% • Bronchoalveolar lavage: BAL alone has a diagnostic yield of 97 to 100 percent in HIV-infected patients. • Transbronchial lung biopsy • Fine needle aspiration • PCR: under investigation

28. Treatment

29. Oral regimens: TMP-SMX, TMP-dapsone, or clindamycin-primaquine for 21 days. • Intravenous regimen: TMP-SMX, Pentamidine, clindamycin-primaquine, trimetraxate. • TMP-SMX is considered the regimen of choice

30. Use of corticosteroids • Patients with PCP typically worsen after two to three days of therapy, presumably due to increased inflammation in response to dying organisms. • Corticosteroids given in conjunction with anti-Pneumocystis therapy decrease the incidence of mortality and respiratory failure associated with severe PCP

31. Treatment failure • Patients who show initial worsening with therapy should start to show clinical improvement around the fifth day of therapy. • Patients who are not showing any improvement after five to seven days of therapy are considered to have treatment failure. • Patients with HIV and severe immunosuppression can have more than one opportunistic infection (OI).

32. HIV infection and mycobacteria infection

33. Interaction between HIV and tuberculosis • HIV-infected patients are at increased risk of developing active TB from both reactivated latent and exogenous infection • An HIV seropositive status is also a risk factor for accelerated progression of TB, particularly in the setting of extensively drug-resistant (XDR) tuberculosis.

34. TB infection is associated with significant increases in plasma HIV viremia • Generalized immune activation, which increases the proportion of CD4 cells that are preferential targets for HIV. • Increased expression of the HIV coreceptors CCR5 and CXCR4.

35. Clinical manifestation: • Extrapulmonary tuberculosis: about 30% • The most common sites of extrapulmonary involvement are blood and extrathoracic lymph nodes, followed by bone marrow, genitourinary tract, and the central nervous system.

36. Radiographic findings: • Patterns typical for primary TB — 36 percent. • Patterns compatible with post-primary (reactivation) TB — 29 percent. • A miliary pattern — 4 percent. • Abnormalities atypical for TB, such as diffuse infiltrates suggestive of PCP — 13 percent. • Minimal changes — 5 percent. • Normal chest radiographs — 14 percent.

37. Most of the patients with CD4 counts greater than 200 cells/mm3 showed post-primary patterns (55 percent). • Patients with fewer than 200 CD4 cells/mm3 were nearly as likely to have normal chest radiographs (21 percent) as they were to have post-primary patterns (23 percent).

38. Radiographic findings on HIV-infected patients with pulmonary tuberculosis

39. Diagnosis: • Tuberculin skin test: CD4 count • Sputum smear and culture for TB • Urine cultures • Stool cultures: helpful to diagnose MAC infection • Invasive tests • Nucleic acid-based amplification assays

40. Effecacy of TB treatment • Therapy for susceptible TB is typically as effective in the HIV-infected patient as it is in the general population. • Although most HIV-infected patients can be successfully treated with standard six-month treatment regimens, longer courses of treatment are indicated for some patients. • These include patients with cavitary disease who remain smear-positive after two months of induction therapy, as well as patients with CNS or skeletal involvement

41. We prefer a rifabutin-based regimen for six months as first-line therapy in HIV-infected patients who are also treated with PIs because of the extensive interactions between rifampin and many antiretroviral drugs.