HIV infection and pulmonary disease

1
HIV infection and pulmonary disease

• Chest ???

2
(No Transcript)
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

• Bacterial pneumonia occurs more frequently in HIV
  seropositive patients, with an annual incidence
  ranging from 5.5 to 29 per 100 compared with 0.9
  to 10 per 100 in HIV seronegative patients.
  Pulmonary Complications of HIV Infection Study
  Group. Hirschtick RE Glassroth J Jordan MC et
  al.N Engl J Med 1995 Sep 28333(13)845-51.
• Bacteria have been reported to account for 3 to
  45 percent of all respiratory infections in
  HIVinfected hosts. 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 May82(5)900-6.

6
(No Transcript)
7

• Among HIVinfected patients, injection drug users
  (IDU), inner city inhabitants, smokers, and
  persons from developing countries are at highest
  risk for bacterial pneumonias. Bacterial
  pneumonia in persons infected with the human
  immunodeficiency virus. Pulmonary Complications
  of HIV Infection Study Group. Hirschtick RE
  Glassroth J Jordan MC et al.N Engl J Med 1995
  Sep 28333(13)845-51. 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 May82(5)900-6.
• The incidence of bacterial pneumonia decreased
  progressively from 1993 to 1996 and 1997 (22.7
  versus 12.3 and 9.1 episodes/100 person-years,
  respectively).

8

• In a multivariate model, use of HAART was
  associated with a 45 percent reduction in the
  risk for bacterial pneumonia.
• Depressed CD4 counts, a prior episode of
  Pneumocystis carinii pneumonia (PCP), and
  injection drug use remained significant risk
  factors for pneumonia regardless of
  antiretroviral therapy. Effect of
  antiretroviral therapy on the incidence of
  bacterial pneumonia in patients with advanced HIV
  infection. Sullivan JH Moore RD Keruly JC
  Chaisson RE. Am J Respir Crit Care Med 2000
  Jul162(1)64-7.

9
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 Jan104(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 416(1)85-95.
10

• 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
  May113(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
  Apr29(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 Sep19(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 Jul18(7)473-7.

11
Pathophysiologic mechanisms underlie the
susceptibility to infection with encapsulated,
pyogenic organisms

• Deficiencies in humoral immunity, including
  HIVrelated 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.

12

• 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
  11165(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.

13

• Nosocomial pneumonia in HIVinfected 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 3101682.
  
  
  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 May82(5)900-6.

14

• 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.

15

• 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 514 in
  large series of nonselected patients hospitalized
  with CAP. from ATS CAP guideline 2007

16

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

17
(No Transcript)
18
Pneumococcal pneumonia (left 2) Staphylococcal
pneumonia (up) H.Influenza pneumonia (Rt
up) K.P pneumonia (Right lower)
19

• 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 117314.

20

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

21
(No Transcript)
22
(No Transcript)
23

• Prevention
• Pneumococcal vaccine
• H. influenzae vaccine
• -- HIB vaccine is not recommended for adults
  infected with HIV
• Prophylactic antibiotics
• -- Trimethoprimsulfamethoxazole has been shown
  to decrease the risk for bacterial infections.
  Hirschtick, R, Glassroth, J, Jordan, M, et al.
  Bacterial pneumonia in persons infected with the
  human immunodeficiency virus. N Engl J Med 1995
  333845.

24

• Macrolide antibiotics are also effective in
  preventing bacterial infections in patients who
  are receiving these agents as prophylaxis for
  Mycobacterium avium complex disease. Havlir, DV,
  Dube, MP, Sattler, FR, et al. Prophylaxis against
  disseminated Mycobacterium avium complex with
  weekly azithromycin, daily rifabutin, or both.
  Califronia Collaborative Treatment Group. N Engl
  J Med 1996 335392.

25
HIV infection and Pneumocystis carinii infection
26

• 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
  10350(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 17261.

27

• 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 15560.
• -- HIV transmission category, age, smoking
  history, and use of antiretroviral therapy did
  not predict development of PCP.

28

• changes in the incidence of PCP
• -- primary prophylaxis against the infection in
  patients with CD4 cell counts lt200/microL
• -- widespread adoption of highly active
  antiretroviral therapy (HAART).
• Hoover, DR, Saah, AJ, Bacellar, H, et al.
  Clinical manifestations of AIDS in the era of
  pneumocystis prophylaxis. Multicenter AIDS Cohort
  Study. N Engl J Med 1993 3291922.
• Wolff, AJ, O'Donnell, AE. Pulmonary
  manifestations of HIV infection in the era of
  highly active antiretroviral therapy. Chest 2001
  1201888.
• San-Andres, FJ, Rubio, R, Castilla, J, et al.
  Incidence of acquired immunodeficiency
  syndrome-associated opportunistic diseases and
  the effect of treatment on a cohort of 1115
  patients infected with human immunodeficiency
  virus, 1989-1997. Clin Infect Dis 2003 361177.

29

• 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 ). Early predictors of in-hospital
  mortality for Pneumocystis carinii pneumonia in
  the acquired immunodeficiency syndrome. Kales
  CP Murren JR Torres RA Crocco JA. Arch Intern
  Med 1987 Aug147(8)1413-7.
• Although fewer patients are receiving aerosolized
  pentamidine as PCP prophylaxis, atypical
  manifestations and extrapulmonary PCP are
  considerations in those receiving this agent.

30

• Radiologic findings
• The most common radiographic abnormalities are
  diffuse, bilateral interstitial or alveolar
  infiltrates. DeLorenzo, LJ, Huang, CT, Maguire,
  GP, Stone, DJ. Roentgenographic patterns of
  Pneumocystis carinii pneumonia in 104 patients
  with AIDS. Chest 1987 91323.
• HRCT 51 patients with suspected PCP and normal,
  equivocal, or nonspecific chest x-ray findings
  HRCT had a sensitivity of 100 percent and a
  specificity of 89 percent when the presence of
  patchy or nodular ground-glass attenuation was
  used to indicate possible PCP. Hartman, TE,
  Primack, SL, Muller, NL, Staples, CA. Diagnosis
  of thoracic complications in AIDS accuracy of
  CT. AJR Am J Roentgenol 1994 162547.

31
(No Transcript)
32

• 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 lt200 cells/mm3
• LDH the mean LDH of PCP survivors was 340 IU,
  while the mean level of non-survivors was 447 IU.
  Zaman, MK, White, DA. Serum lactate
  dehydrogenase levels and Pneumocystis carinii
  pneumonia Diagnostic and prognostic
  significance. Am Rev Respir Dis 1988 137796.

33

• Clinical course
• Patients with PCP frequently worsen, with an
  increase in the alveolar-arterial oxygen
  gradient, two to three days after starting
  anti-Pneumocystis therapy, presumably because of
  increased inflammation in the lungs as organisms
  are killed.
• This worsening can often be prevented or blunted
  with corticosteroids that are administered at the
  initiation of therapy.

34

• Diagnosis of PCP infection
• Sputum sensivity 55-92 specificity 100
  Zaman, MK, Wooten, OJ, Suprahmanya, B,
  et al. Rapid non-invasive diagnosis of
  Pneumocystis carinii from induced liquified
  sputum. Ann Intern Med 1988 1097.
  
  
  Cruciani, M, Marcati, P,
  Malena, M, et al. Meta-analysis of diagnostic
  procedures for Pneumocystis carinii pneumonia in
  HIV-1-infected patients. Eur Respir J 2002
  20982.
• Bronchoalveolar lavage BAL alone has a
  diagnostic yield of 97 to 100 percent in
  HIV-infected patients. Jules-Elysee, K, Stover,
  DE, Zaman, MB, et al. Aerosolized pentamidine
  Effect on diagnosis and presentation of
  Pneumocystis carinii pneumonia. Ann Intern Med
  1990 112750.
• Transbronchial lung biopsy
• Fine needle aspiration
• PCR under investigation

35
Treatment
36

• Oral regiments TMP-SMX, TMP-dapsone, or
  clindamycin-primaquine for 21 days.
• Intravenous regiment TMP-SMX, Pentamidine,
  clindamycin-primaquine, trimetraxate.
• TMP-SMX is considered the regimen of choice for
  intravenous therapy of PCP.

37

• Isolation There is evidence that person to
  person transmission of PCP is more common than
  was previously thought. Kovacs, JA, Masur, H.
  Prophylaxis against opportunistic infections in
  patients with human immunodeficiency virus
  infection. N Engl J Med 2000 3421416.
• Pregnancy As in other patients, TMP-SMX is the
  preferred therapy in pregnant women other
  therapies such as TMP-dapsone may also be used.
  Benson, C, Kaplan, J, Masur, H, et. al. Treating
  opportunistic infections among HIV-infected
  adults and adolescents recommendations from CDC,
  the National Institutes of Health, and the HIV
  Medicine Association/Infectious Diseases Society
  of America. Clin Infect Dis 2005 40S131.

38

• 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. Adjunctive corticosteroids for
  Pneumocystis jiroveci pneumonia in patients with
  HIV-infection. Briel M Bucher H Boscacci R
  Furrer H. Cochrane Database Syst Rev. 2006 Jul
  193CD006150.

39

• Those recommendations that patients should
  receive corticosteroid therapy if, while
  breathing room air, an arterial blood gas
  measurement shows either
• -- A partial pressure of oxygen of 70 mmHg or
  less
• -- An alveolar-arterial (A-a) oxygen gradient of
  35 mmHg or more
• Consensus statement on the use of
  corticosteroids as adjunctive therapy for
  pneumocystis pneumonia in the acquired
  immunodeficiency syndrome. The National
  Institutes of Health-University of California
  Expert Panel for Corticosteroids as Adjunctive
  Therapy for Pneumocystis Pneumonia. N Engl J Med
  1990 3231500.

40

• Regimens of corticosteroids (21 days course)
• Prednisone 40 mg twice daily for five days
• followed by
• Prednisone 40 mg daily for five days
• followed by
• Prednisone 20 mg daily for 11 days

41

• 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).

42

• Prognosis
• The degree of hypoxemia at presentation is
  strongly related to the prognosis of PCP.
  Prognostic factors influencing the outcome in
  pneumocystis carinii pneumonia in patients with
  AIDS. Fernandez P Torres A Miro JM Vieigas C
  Mallolas J Zamora L Gatell JM Valls ME
  Riquelme R Rodriguez-Roisin R . Thorax. 1995
  Jun50(6)668-71.
• Other correlates with worse outcome include
  increasing age, prior episodes of PCP, an
  elevated serum lactate dehydrogenase
  concentration, low CD4 cell count, and the
  presence of cytomegalovirus in bronchoalveolar
  lavage fluid. Dworkin, MS, Hanson, DL, Navin,
  TR. Survival of patients with AIDS, after
  diagnosis of Pneumocystis carinii pneumonia, in
  the United States. J Infect Dis 2001 1831409.
  Benfield, TL, Helweg-Larsen, J, Bang, D, et al.
  Prognostic markers of short-term mortality in
  AIDS-associated Pneumocystis carinii pneumonia.
  Chest 2001 119844.

43
HIV infection and mycobacteria infection
44

• Interaction between HIV and tuberculosis
• HIV-infected patients are at increased risk of
  developing active TB from both reactivated latent
  and exogenous infection. Barnes, PF, Bloch, AB,
  Davidson, PT, Snider, DE. Tuberculosis in
  patients with human immunodeficiency virus
  infection. N Engl J Med 1991 3241644.
• An HIV seropositive status is also a risk factor
  for accelerated progression of TB, particularly
  in the setting of extensively drug-resistant
  (XDR) tuberculosis. Shuchman, M. Improving
  global health--Margaret Chan at the WHO. N Engl J
  Med 2007 356653.

45

• TB infection is associated with significant
  increases in plasma HIV viremia Toossi, Z,
  Mayanja-Kizza, H, Hirsch, CS, et al. Impact of
  tuberculosis (TB) on HIV-1 activity in dually
  infected patients. Clin Exp Immunol 2001
  123233.
• -- Generalized immune activation, which increases
  the proportion of CD4 cells that are preferential
  targets for HIV. Vanham, G, Edmonds, K, Qing, L,
  et al. Generalized immune activation in pulmonary
  tuberculosis co-activation with HIV infection.
  Clin Exp Immunol 1996 10330.
• -- Increased expression of the HIV coreceptors
  CCR5 and CXCR4. Wolday, D, Tegbaru, B, Kassu, A,
  et al. Expression of chemokine receptors CCR5 and
  CXCR4 on CD4 T cells and plasma chemokine levels
  during treatment of active tuberculosis in
  HIV-1-coinfected patients. J Acquir Immune Defic
  Syndr 2005 39265.

46

• Impact of HAART
• HAART reduces the risk of developing TB. Lawn,
  SD, Bekker, LG, Wood, R. How effectively does
  HAART restore immune responses tonMycobacterium
  tuberculosis? Implications for tuberculosis
  control. AIDS 2005 191113.
• The greatest risk factor for the development of
  TB on HAART is the pretreatment level of
  immunodeficiency, as reflected by the baseline
  CD4 cell count the CD4 cell count at six months
  after initiation of HAART is also associated with
  an increased risk of TB. Girardi, E, Sabin, CA,
  d'Arminio Monforte, A, et al. Incidence of
  Tuberculosis among HIV-infected patients
  receiving highly active antiretroviral therapy in
  Europe and North America. Clin Infect Dis 2005
  411772.

47

• 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. Barnes,
  PF, Bloch, AB, Davidson, PT, Snider, DE.
  Tuberculosis in patients with human
  immunodeficiency virus infection. N Engl J Med
  1991 3241644. Jones, BA, Young, SMM,
  Antoniskis, D, et al. Relationship of the
  manifestations of tuberculosis to CD4 cell counts
  in patients with human immunodeficiency virus
  infection. Am Rev Respir Dis 1993 1481292.

48

• 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.
• Greenberg, SD, Frager, D, Suster, B, et al.
  Active pulmonary tuberculosis in patients with
  AIDS Spectrum of radiographic findings
  (including a normal appearance). Radiology 1994
  193115.

49

• 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).

50
Active pulmonary tuberculosis in patients with
AIDS Spectrum of radiographic findings
(including a normal appearance). Radiology 1994
193115.
51
Clinical and radiographic correlates of primary
andreactivation tuberculosis a molecular
epidemiology study. Geng, E, Kreiswirth, B,
Burzynski, J, Schluger, NW. JAMA 2005 2932740.
52
Radiographic findings on HIV-infected patients
with pulmonary tuberculosis
53

• 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

54

• 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

55

• Relapse rates after short-course (6-month)
  treatment of tuberculosis in HIV-infected and
  uninfected persons. AIDSVolume 13(14)1 October
  1999pp 1899-1904

56

• Virological Response to Highly Active
  Antiretroviral Therapy Is Unaffected by
  Antituberculosis Therapy. J Infect Dis 2006
  1931437
• No difference in virological response was seen
  between the patients with HIV and tuberculosis
  and the control group.
• Fourteen (13) of 111 patients with HIV infection
  and tuberculosis failed to achieve a virus load
  of lt 400 copies/mL within 6 months of starting
  HAART, compared with 13 (12) of 111 persons
  without tuberculosis (P.84)

57

• 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.