HIV AIDS opportunistic infections: Difference between revisions

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==Guidelines==
==Guidelines==
*HIV-infected adults and adolescents, including pregnant women and those on ART, should receive chemoprophylaxis against PCP if they have a CD4+ count of <200 cells/µL ('''AI''') or a history of oropharyngeal candidiasis ('''AII''').
*HIV-infected adults and adolescents, including pregnant women and those on ART, should receive chemoprophylaxis against PCP if they have a CD4+ count of <200 cells/µL ('''AI''') or a history of oropharyngeal candidiasis ('''AII''').<ref name="pmid1967190">{{cite journal |author=Phair J, Muñoz A, Detels R, Kaslow R, Rinaldo C, Saah A |title=The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group |journal=N. Engl. J. Med. |volume=322 |issue=3 |pages=161–5 |year=1990 |month=January |pmid=1967190 |doi=10.1056/NEJM199001183220304 |url=http://dx.doi.org/10.1056/NEJM199001183220304 |accessdate=2012-04-06}}</ref>


==Related Chapters==
==Related Chapters==

Revision as of 18:52, 6 April 2012

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief:, Ujjwal Rastogi, MBBS [2]

Overview

Before the widespread use of potent combination antiretroviral therapy (ART), opportunistic infections (OIs), which have been defined as infections that are more frequent or more severe because of immunosuppression in HIV-infected persons, were the principal cause of morbidity and mortality in this population. In the early 1990s, the use of chemoprophylaxis, immunization, and better strategies for managing acute OIs contributed to improved quality of life and improved survival.[1] However, the widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable.

Etiology

Despite the availability of ART in the United States and other industrialized countries, OIs continue to cause considerable morbidity and mortality for three primary reasons:

  • Many patients are unaware of their HIV infection and seek medical care when an OI becomes the initial indicator of their disease.
  • Certain patients are aware of their HIV infection, but do not take ART because of psychosocial or economic factors.
  • Certain patients are prescribed ART, but fail to attain adequate virologic and immunologic response because of factors related to adherence, pharmacokinetics, or unexplained biologic factors.[2][3]

Thus, although hospitalizations and deaths have decreased since the implementation of ART, OIs remain a leading cause of morbidity and mortality in HIV-infected persons.[4][5][6]

Pathophysiology

Recognizing that the relation between OIs and HIV infection is bidirectional is important. HIV leads to immunosuppression that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs and other coinfections that might be common in HIV-infected persons, such as sexually transmitted infections, can also have adverse effects on the natural history of HIV infection. Certain OIs are associated with reversible increases in circulating viral load and these increases could lead to accelerated HIV progression or increased transmission of HIV. Thus, although chemoprophylaxis and vaccination directly prevent pathogen-specific morbidity and mortality, they might also contribute to reduced rate of progression of HIV disease. For instance, randomized trials using trimethoprim-sulfamethoxazole (TMP-SMX) have documented that chemoprophylaxis can both decrease OI-related morbidity and improve survival.

Historical Perspective

The first guidelines for Prophylaxis against Pneumocystis carinii Pneumonia for persons infected with the human immunodeficiency virus became the first HIV-related treatment guideline published by the U.S. Public Health Service in 1989. This report was followed by guideline on prevention of Mycobacterium avium complex (MAC) disease in 1993.

Treatment

Initiation of ART in the Setting of an Acute OI (Treatment-Naïve Patients)

When an acute OI is present, initiation of ART is usually expected to improve immune function and contribute to faster resolution of the OI.

Initiation of ART has been documented to be effective for OIs for which effective therapy does not exist; cryptosporidiosis, microsporidiosis, and progressive multifocal leukoencephalopathy (PML) might resolve or at least stabilize after the institution of effective ART. For kaposi's sarcoma (KS), initiation of ART has been documented to lead to resolution of lesions in the absence of specific therapy for the sarcoma.[7]

Benefits of ART in preventing OI:

The initiation of ART in the setting of an acute OI also has preventive benefit; a second OI is less likely to occur if ART is started promptly rather than delaying the initiation of ART.

Disadvantages:

Starting ART in the setting of an acute OI has several potential disadvantages.

  • Severely ill patients might not absorb ART drugs, leading to subtherapeutic serum levels and the development of antiretroviral drug resistance.
  • ART toxicities might be confused with disease manifestations or toxicities associated with drugs used for treating patients with an OI. Drug-drug interactions among ART and anti-OI drugs might be difficult to manage.
  • Renal or hepatic dysfunction during acute OIs might make dosing of ART drugs difficult to estimate.
  • IRIS events can occur and cause manifestations that are difficult to distinguish from other clinical conditions.

When to start the therapy?

For above mentioned reasons, no consensus has been reached concerning the optimal time to start ART in the setting of a recently diagnosed OI. However, one recently completed randomized clinical trial has demonstrated a clinical and survival benefit of starting ART early, within the first 2 weeks, of initiation of treatment for an acute OI, excluding TB.[8]

Management of Acute OIs in Patients Receiving ART

OIs that occur after patients have been started on ART can be categorized into three groups.

  • The first group includes OIs that occur shortly after initiating ART (within 12 weeks).
    • These cases might be subclinical infections that have been unmasked by early immune reconstitution or simply OIs that occurred because of advanced immunosuppression and are not considered to represent early failure of ART. Many of these cases represent IRIS.[9][10]
    • When an OI occurs within 12 weeks of starting ART, treatment for the OI should be started and ART should be continued.
  • The second group includes OIs that occur >12 weeks after initiation of ART among patients with suppressed HIV ribonucleic acid. levels and sustained CD4+ counts >200 cells/µL[11][12] Determining whether these represent a form of IRIS rather than incomplete immunity with the occurrence of a new OI is difficult.
    • When an OI occurs despite complete virologic suppression (i.e., late OI), therapy for the OI should be initiated and ART should be continued.
    • If the CD4+ response to ART has been suboptimal, modification of the ART regimen may be considered, although no evidence exists to indicate that changing the ART regimen in this setting will improve the CD4+ response.
  • The third group includes OIs that occur among patients who are experiencing virologic and immunologic failure while on ART. These represent clinical failure of ART.
    • When an OI occurs in the setting of virologic failure, OI therapy should be started, antiretroviral resistance testing should be performed, and the ART regimen should be modified, if possible, to achieve better virologic control.

Special Considerations During Pregnancy

Physiologic changes during pregnancy can complicate the recognition of OIs and complicate pharmacokinetics. Factors to consider include the following:

  • Increased cardiac output by 30%--50% with concomitant increase in glomerular filtration rate and renal clearance.
  • Increased plasma volume by 45%--50% while red cell mass increases only by 20%--30%, leading to dilutional anemia.
  • Tidal volume and pulmonary blood flow increase, possibly leading to increased absorption of aerosolized medications. The tidal volume increase of 30%--40% should be considered if ventilatory assistance is required.
  • Placental transfer of drugs, increased renal clearance, altered gastrointestinal absorption, and metabolism by the fetus might affect maternal drug levels.
  • Limited pharmacokinetic data are available; use usual adult doses based on current weight, monitor levels if available, and consider the need to increase doses if the patient is not responding as expected.

Also in regards with risk in Fetus, pregnancy should not preclude usual diagnostic evaluation when an OI is suspected.[13][14][15] Experience with use of magnetic resonance imaging (MRI) in pregnancy is limited, but no adverse fetal effects have been noted.[13]

Guidelines

  • HIV-infected adults and adolescents, including pregnant women and those on ART, should receive chemoprophylaxis against PCP if they have a CD4+ count of <200 cells/µL (AI) or a history of oropharyngeal candidiasis (AII).[16]

Related Chapters

Reference

  1. ↑ Walensky RP, Paltiel AD, Losina E, Mercincavage LM, Schackman BR, Sax PE, Weinstein MC, Freedberg KA (2006). "The survival benefits of AIDS treatment in the United States". J. Infect. Dis. 194 (1): 11–9. doi:10.1086/505147. PMID 16741877. Retrieved 2012-04-05. Unknown parameter |month= ignored (help)
  2. ↑ Perbost I, Malafronte B, Pradier C, Santo LD, Dunais B, Counillon E, Vinti H, Enel P, Fuzibet JG, Cassuto JP, Dellamonica P (2005). "In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection?". HIV Med. 6 (4): 232–9. doi:10.1111/j.1468-1293.2005.00282.x. PMID 16011527. Retrieved 2012-04-05. Unknown parameter |month= ignored (help)
  3. ↑ Palacios R, Hidalgo A, Reina C, de la Torre M, Márquez M, Santos J (2006). "Effect of antiretroviral therapy on admissions of HIV-infected patients to an intensive care unit". HIV Med. 7 (3): 193–6. doi:10.1111/j.1468-1293.2006.00353.x. PMID 16494634. Retrieved 2012-04-05. Unknown parameter |month= ignored (help)
  4. ↑ Gebo KA, Fleishman JA, Reilly ED, Moore RD (2005). "High rates of primary Mycobacterium avium complex and Pneumocystis jiroveci prophylaxis in the United States". Med Care. 43 (9 Suppl): III23–30. PMID 16116306. Retrieved 2012-04-05. Unknown parameter |month= ignored (help)
  5. ↑ Bonnet F, Lewden C, May T, Heripret L, Jougla E, Bevilacqua S, Costagliola D, Salmon D, Chêne G, Morlat P (2005). "Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France". Scand. J. Infect. Dis. 37 (6–7): 482–7. PMID 16089023. |access-date= requires |url= (help)
  6. ↑ Teshale EH, Hanson DL, Wolfe MI, Brooks JT, Kaplan JE, Bort Z, Sullivan PS (2007). "Reasons for lack of appropriate receipt of primary Pneumocystis jiroveci pneumonia prophylaxis among HIV-infected persons receiving treatment in the United States: 1994-2003". Clin. Infect. Dis. 44 (6): 879–83. doi:10.1086/511862. PMID 17304464. Retrieved 2012-04-05. Unknown parameter |month= ignored (help)
  7. ↑ Murdaca G, Campelli A, Setti M, Indiveri F, Puppo F (2002). "Complete remission of AIDS/Kaposi's sarcoma after treatment with a combination of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitor". AIDS. 16 (2): 304–5. PMID 11807324. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  8. ↑ Jacobson MA, Zegans M, Pavan PR, O'Donnell JJ, Sattler F, Rao N, Owens S, Pollard R (1997). "Cytomegalovirus retinitis after initiation of highly active antiretroviral therapy". Lancet. 349 (9063): 1443–5. doi:10.1016/S0140-6736(96)11431-8. PMID 9164318. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  9. ↑ Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, Costagliola D, D'Arminio Monforte A, de Wolf F, Reiss P, Lundgren JD, Justice AC, Staszewski S, Leport C, Hogg RS, Sabin CA, Gill MJ, Salzberger B, Sterne JA (2002). "Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies". Lancet. 360 (9327): 119–29. PMID 12126821. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  10. ↑ Race EM, Adelson-Mitty J, Kriegel GR, Barlam TF, Reimann KA, Letvin NL, Japour AJ (1998). "Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease". Lancet. 351 (9098): 252–5. doi:10.1016/S0140-6736(97)04352-3. PMID 9457095. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  11. ↑ Currier JS, Williams PL, Koletar SL, Cohn SE, Murphy RL, Heald AE, Hafner R, Bassily EL, Lederman HM, Knirsch C, Benson CA, Valdez H, Aberg JA, McCutchan JA (2000). "Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team". Ann. Intern. Med. 133 (7): 493–503. PMID 11015162. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  12. ↑ Cinti SK, Kaul DR, Sax PE, Crane LR, Kazanjian PH (2000). "Recurrence of Mycobacterium avium infection in patients receiving highly active antiretroviral therapy and antimycobacterial agents". Clin. Infect. Dis. 30 (3): 511–4. doi:10.1086/313705. PMID 10722436. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  13. ↑ 13.0 13.1 "ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158, September 1995). Guidelines for diagnostic imaging during pregnancy". Obstet Gynecol. 104 (3): 647–51. 2004. PMID 15339791. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  14. ↑ Toppenberg KS, Hill DA, Miller DP (1999). "Safety of radiographic imaging during pregnancy". Am Fam Physician. 59 (7): 1813–8, 1820. PMID 10208701. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  15. ↑ Adelstein SJ (1999). <236::AID-TERA9>3.0.CO;2-6 "Administered radionuclides in pregnancy". Teratology. 59 (4): 236–9. doi:10.1002/(SICI)1096-9926(199904)59:4<236::AID-TERA9>3.0.CO;2-6. PMID 10331526. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
  16. ↑ Phair J, Muñoz A, Detels R, Kaslow R, Rinaldo C, Saah A (1990). "The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1. Multicenter AIDS Cohort Study Group". N. Engl. J. Med. 322 (3): 161–5. doi:10.1056/NEJM199001183220304. PMID 1967190. Retrieved 2012-04-06. Unknown parameter |month= ignored (help)
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