Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents
Last Updated: June 17, 2013; Last Reviewed: May 7, 2013
Prior to 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,1,2 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.3 Subsequently, the widespread use of potent ART has had the most profound influence on reducing OI-related mortality in HIV-infected persons.3-10
Despite the availability of ART, OIs continue to cause considerable morbidity and mortality in the United States for three main reasons:
- Approximately 20% of HIV-infected persons in the United States are unaware of their HIV infection,11,12 and many present with an OI as the initial indicator of their disease;13
- Some individuals are aware of their HIV infection, but do not take ART due to psychosocial or economic factors; and
- Some patients are enrolled in HIV care and prescribed ART, but do not attain an adequate virologic and immunologic response due to inconsistent retention in care, poor adherence, unfavorable pharmacokinetics, or unexplained biologic factors.6,14,15
Recent analyses suggest that while 77% of HIV-infected persons who are retained in care and prescribed ART are virologically suppressed, only 20% to 28% of the total estimated HIV-infected population in the United States are virologically suppressed,11,16 with as few as 10% in some jurisdictions.17 Thus, while hospitalizations and deaths have decreased dramatically due to ART, OIs continue to cause substantial morbidity and mortality in HIV-infected persons.18-28 Clinicians must be knowledgeable about optimal strategies for diagnosis, prevention, and treatment of OIs to provide comprehensive, high quality care for these patients.
It is important to recognize that the relationship between OIs and HIV infection is bi-directional. HIV causes the immunosuppression that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs, as well as other co-infections that may be common in HIV-infected persons, such as sexually transmitted infections (STIs), can adversely affect the natural history of HIV infection by causing reversible increases in circulating viral load29-34 that could accelerate HIV progression and increase transmission of HIV.35 Thus, while chemoprophylaxis and vaccination directly prevent pathogen-specific morbidity and mortality, they may also contribute to reduced rate of progression of HIV disease. For instance, randomized trials have shown that chemoprophylaxis with trimethoprim-sulfamethoxazole can both decrease OI-related morbidity and improve survival. The survival benefit is likely to result, in part, from reduced progression of HIV infection.36-40 In turn, the reduced progression of HIV infection would reduce the risk of subsequent OIs.
History of These Guidelines
In 1989, the 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.41 This publication was followed by a guideline on prevention of Mycobacterium avium complex disease in 1993.42 In 1995 these guidelines were expanded to include the prevention of all HIV-related OIs and the Infectious Diseases Society of America (IDSA) joined as a co-sponsor.43 These prevention guidelines were revised in 1997, 1999, and 2002 and were published in Morbidity and Mortality Weekly Report (MMWR),44-46 Clinical Infectious Diseases,47-49 The Annals of Internal Medicine,50,51 American Family Physician,52,53 and Pediatrics;54 accompanying editorials appeared in the Journal of the American Medical Association (JAMA)2,55 and in Topics in HIV Medicine.56
In 2004 the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the IDSA published a new guideline including recommendations for treating OIs among HIV-infected adults and adolescents.57 Companion guidelines were published for HIV-infected children.58 Revised guidelines for both prevention and treatment of OIs in HIV-infected adults and adolescents59 and HIV-exposed/infected children60 were published in 2009.
Responses to these guidelines (e.g., numbers of requests for reprints, website contacts) demonstrate that these documents are valuable references for HIV health care providers. The inclusion of ratings that indicate both the strength of each recommendation and the quality of supporting evidence allows readers to assess the relative importance of each recommendation. The present revision includes recommendations for prevention and treatment of OIs in HIV-infected adults and adolescents; a revision of recommendations for HIV-exposed and infected children can also be found in https://aidsinfo.nih.gov.
These guidelines are intended for clinicians, other health care providers, HIV-infected patients, and policy makers in the United States; guidelines pertinent to other regions of the world, especially resource-limited countries, may differ with respect to the spectrum of OIs of interest and diagnostic and therapeutic capacities.
Guidelines Development Process
These guidelines were prepared by the Opportunistic Infections Working Group under the auspices of the Office of AIDS Research Advisory Council (OARAC) of the NIH. Briefly, six co-editors selected and appointed by their respective agencies (i.e., NIH, CDC, IDSA) convened working groups of clinicians and scientists with subject matter expertise in specific OIs. The co-editors appointed a leader for each working group, which reviewed the literature since the last publication of these guidelines, conferred over a period of several months, and produced draft revised recommendations. Issues requiring specific attention were reviewed and discussed by the co-editors and the leaders from each working group at the annual meeting of the IDSA in Vancouver, Canada, in October 2010. After further revision, the guidelines were reviewed by patient care advocates and by primary care providers with extensive experience in the management of HIV infection. The final document reflects further revision by the co-editors, the Office of AIDS Research (OAR), experts at CDC, and by the IDSA and affiliated HIV Medicine Association prior to final approval and publication on the AIDSinfo website. The names and affiliations of all contributors as well as their financial disclosures are provided in the Panel roster and Financial Disclosure section. The names of the patient advocates and primary HIV care providers who reviewed the document are listed in the Contributors (Appendix D).
|Goal of the guidelines
||Provide guidance to HIV care practitioners on the optimal prevention and management of HIV-related opportunistic infections (OIs) for adults and adolescents in the United States.
||The panel is composed of six co-editors who represent the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Disease Society of America (HIVMA/IDSA), plus more than 100 members who have expertise in HIV clinical care, infectious disease management, and research. Co-editors are appointed by their respective agencies or organizations. Panel members are selected from government, academia, and the healthcare community by the co-editors and assigned to a working group for one or more the guideline’s sections based on the member’s area of subject mater expertise. Each working group is chaired by a single panel member selected by the co-chairs. Members serve on the panel for a 4-year term, with an option to be reappointed for additional terms. The panel co-editors also select members from the community of persons affected by HIV disease (i.e., adults living with HIV infection, advocates for persons living with HIV infection) to review the entire guidelines document. The list of the current panel members and of the patient advocates and primary HIV care providers who reviewed the document can be found in Appendices C and D, respectively.
|Financial disclosure and management of conflicts of interest
||All members of the panel submit a written financial disclosure annually reporting any associations with manufacturers of drugs, vaccines, medical devices, or diagnostics used to manage HIV-related OIs. A list of these disclosures and their last update is available in Appendix C. The panel co-editors review each reported association for potential conflict of interest and determine the appropriate action: disqualification from the panel, disqualification/recusal from topic review and discussion; no disqualification needed. A conflict of interest is defined as any direct financial interest related to a product addressed in the section of the guideline to which a panel member contributes content. Financial interests include direct receipt by the panel member of payments, gratuities, consultancies, honoraria, employment, grants, support for travel or accommodation, or gifts from an entity having a commercial interest in that product. Financial interest also includes direct compensation for membership on an advisory board, data safety monitoring board, or speakers’ bureau. Compensation and support that filters through a panel member’s university or institution (e.g., grants, research funding) is not considered a conflict of interest.
|Users of the guidelines
||HIV treatment providers
||Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents—a working group of the Office of AIDS Research Advisory Council (OARAC).
||The Office of AIDS Research (OAR), NIH
||The recommendations in the guidelines are generally based on studies published in peer-reviewed journals. On some occasions, particularly when new information may affect patient safety, unpublished data presented at major conferences or information prepared by the U.S. Food and Drug Administration or manufacturers (e.g., warnings to the public) may be used as evidence to revise the guidelines. Panel members of each working group are responsible for conducting a systematic comprehensive review of the literature, for conducting updates of that review, and for bringing to their working group’s attention all relevant literature.
|Method of synthesizing data and formulating recommendations
||Each section of the guidelines is assigned to a working group of panel members with expertise in the area of interest. The members of the working group synthesize the available data. Recommendations are reviewed and updated by each working group after an assessment of the quality and impact of the existing and any new data. Aspects of evidence that are considered include but are not necessarily limited to the type of study (e.g., case series, prospective cohort, randomized controlled trial), the quality and appropriateness of the methods, and the number of subjects and effect sizes observed. Each revision of the guidelines is reviewed by patient care advocates and by primary care providers with extensive experience in the management of HIV infection to assess cultural sensitivity and operational utility. Finally, all material is reviewed by the co-editors, OAR, subject matter experts at CDC and the HIVMA/IDSA prior to final approval and publication.
||Recommendations are rated using a revised version of the previous rating system (see How to Use the Information in this Report and Rating System for Prevention and Treatment Recommendations, below) and accompanied, as needed, by explanatory text that reviews the evidence and the working group’s assessment. All proposals are discussed at teleconferences and by email and then assessed by the panel’s co-editors and reviewed by OAR, CDC, and the HIVMA/IDSA before being endorsed as official recommendations.
||These guidelines focus on prevention and treatment of HIV-related OIs for adults and adolescents. A separate guideline outlines similar recommendations for HIV-infected and exposed children. These guidelines are also available on the AIDSinfo website (https://aidsinfo.nih.gov).
||Each work group and the co-editors meet at least every 6 months by teleconference to review data that may warrant modification of the guidelines. Updates may be prompted by approvals of new drugs, vaccines, medical devices or diagnostics, by new information regarding indications or dosing, by new safety or efficacy data, or by other information that may affect prevention and treatment of HIV-related OIs. Updates that may significantly affect patient safety or treatment and that warrant rapid notification may be posted temporarily on the AIDSinfo website (https://aidsinfo.nih.gov) until appropriate changes can be made in the guidelines document.
||After release of an update on the AIDSinfo website, the public is given a 2-week period to submit comments to the panel. These comments are reviewed, and a determination is made by the appropriate work group and the co-editors as to whether revisions are indicated. The public may also submit comments to the Panel at any time at email@example.com.|
Major Changes in Guidelines Since Last PublicationMajor changes in the document include:
- New information on when to start ART in the setting of an acute OI, including tuberculosis;
- When to start therapy for hepatitis B and hepatitis C disease, and what drugs to use;
- Drug interactions between drugs used to manage OIs and HIV;
- A change in the system for rating the strength of each recommendation, and the quality of evidence supporting that recommendation (see Rating System for Prevention and Treatment Recommendations); and
- Inclusion of pathogen-specific tables of recommended prevention and treatment options at the end of each OI section, in addition to summary tables at the end of the document.
How to Use the Information in this ReportRecommendations in this report address:
- Preventing exposure to opportunistic pathogens;
- Preventing disease;
- Discontinuing primary prophylaxis after immune reconstitution;
- Treating disease;
- When to start ART in the setting of an acute OI;
- Monitoring for adverse effects (including immune reconstitution inflammatory syndrome [IRIS]);
- Managing treatment failure;
- Preventing disease recurrence (“secondary prophylaxis” or chronic maintenance therapy);
- Discontinuing secondary prophylaxis after immune reconstitution; and
- Special considerations during pregnancy.
|Strength of Recommendation
||Quality of Evidence for the Recommendation|
|A: Strong recommendation for the statement
B: Moderate recommendation for the statement
C: Optional recommendation for the statement
|I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints
II: One or more well-designed, non-randomized trials or observational cohort studies with long-term clinical outcomes
III: Expert opinion
This document also includes tables in each OI section pertinent to the prevention and treatment of OIs, as well as eight summary tables at the end of the document (Tables 1–8), a figure that includes immunization recommendations, and an appendix that summarizes recommendations pertinent to preventing exposure to opportunistic pathogens, including preventing exposure to STIs (Appendix A).
Special Considerations Regarding Pregnancy
No large studies have been conducted concerning the epidemiology or manifestations of HIV-associated OIs among pregnant women. No data demonstrate that the spectrum of OIs differs from that among non-pregnant women with comparable CD4+ counts.
Physiologic changes during pregnancy can complicate the recognition of OIs and complicate treatment due to changes in pharmacokinetic parameters, which may influence optimal dosing for drugs used for prevention or treatment of OI. Factors to consider include the following:61
- Increased cardiac output by 30% to 50% with concomitant increase in glomerular filtration rate and renal clearance.
- Increased plasma volume by 45% to 50% while red cell mass increases only by 20% to 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% to 40% should be considered if ventilator assistance is required.
- Placental transfer of drugs, increased renal clearance, altered gastrointestinal absorption, and metabolism by the fetus that 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.
Other procedures necessary for diagnosis of suspected OIs should be performed in pregnancy as indicated for non-pregnant patients. A pregnant woman who is >20 weeks of gestation should not lie flat on her back but should have her right hip elevated with a wedge to displace the uterus off the great vessels and prevent supine hypotension. Oxygenation should be monitored when pregnant patients are positioned such that ventilation or perfusion might be compromised.
In the United States, pregnancy is an indication to start antiretroviral therapy if the HIV-infected woman is not already on therapy. A decision to defer therapy based on a current or recent OI should be made on the same basis as for non-pregnant individuals supplemented by consultation with the obstetrician regarding factors unique to each individual pregnancy.
After first-trimester exposure to agents of uncertain teratogenic potential, including many of the anti-infective agents described in this guideline, an ultrasound should be conducted every 4 to 6 weeks in the third trimester to assess fetal growth and fluid volume, with antepartum testing if growth lag or decreased fluid are noted.
- Kaplan JE, Masur H, Holmes KK, et al. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: introduction. USPHS/IDSA Prevention of Opportunistic Infections Working Group. Clin Infect Dis. Aug 1995;21 Suppl 1:S1-11. Available at http://www.ncbi.nlm.nih.gov/pubmed/8547495.
- Kaplan JE, Masur H, Jaffe HW, Holmes KK. Reducing the impact of opportunistic infections in patients with HIV infection. New guidelines. JAMA. Jul 26 1995;274(4):347-348. Available at http://www.ncbi.nlm.nih.gov/pubmed/7609267.
- Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis. Jul 1 2006;194(1):11-19. Available at http://www.ncbi.nlm.nih.gov/pubmed/16741877.
- Palella FJ, Jr., Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. Mar 26 1998;338(13):853-860. Available at http://www.ncbi.nlm.nih.gov/pubmed/9516219.
- Detels R, Munoz A, McFarlane G, et al. Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators. JAMA. Nov 4 1998;280(17):1497-1503. Available at http://www.ncbi.nlm.nih.gov/pubmed/9809730.
- Jones JL, Hanson DL, Dworkin MS, et al. Surveillance for AIDS-defining opportunistic illnesses, 1992-1997. MMWR. CDC surveillance summaries : Morbidity and mortality weekly report. CDC surveillance summaries / Centers for Disease Control. Apr 16 1999;48(2):1-22. Available at http://www.ncbi.nlm.nih.gov/pubmed/12412613.
- Mocroft A, Vella S, Benfield TL, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet. Nov 28 1998;352(9142):1725-1730. Available at http://www.ncbi.nlm.nih.gov/pubmed/9848347.
- McNaghten AD, Hanson DL, Jones JL, Dworkin MS, Ward JW. Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group. AIDS. Sep 10 1999;13(13):1687-1695. Available at http://www.ncbi.nlm.nih.gov/pubmed/10509570.
- Miller V, Mocroft A, Reiss P, et al. Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1 disease progression: results from the EuroSIDA study. Ann Intern Med. Apr 6 1999;130(7):570-577. Available at http://www.ncbi.nlm.nih.gov/pubmed/10189326.
- Dore GJ, Li Y, McDonald A, Ree H, Kaldor JM, National HIVSC. Impact of highly active antiretroviral therapy on individual AIDS-defining illness incidence and survival in Australia. J Acquir Immune Defic Syndr. Apr 1 2002;29(4):388-395. Available at http://www.ncbi.nlm.nih.gov/pubmed/11917244.
- Centers for Disease C, Prevention. Vital signs: HIV prevention through care and treatment--United States. MMWR Morb Mortal Wkly Rep. Dec 2 2011;60(47):1618-1623. Available at http://www.ncbi.nlm.nih.gov/pubmed/22129997.
- Campsmith ML, Rhodes PH, Hall HI, Green TA. Undiagnosed HIV prevalence among adults and adolescents in the United States at the end of 2006. J Acquir Immune Defic Syndr. Apr 2010;53(5):619-624. Available at http://www.ncbi.nlm.nih.gov/pubmed/19838124.
- Seal PS, Jackson DA, Chamot E, et al. Temporal trends in presentation for outpatient HIV medical care 2000-2010: implications for short-term mortality. J Gen Intern Med. Jul 2011;26(7):745-750. Available at http://www.ncbi.nlm.nih.gov/pubmed/21465301.
- Perbost I, Malafronte B, Pradier C, et al. In the era of highly active antiretroviral therapy, why are HIV-infected patients still admitted to hospital for an inaugural opportunistic infection? HIV Med. Jul 2005;6(4):232-239. Available at http://www.ncbi.nlm.nih.gov/pubmed/16011527.
- Palacios R, Hidalgo A, Reina C, de la Torre M, Marquez M, Santos J. Effect of antiretroviral therapy on admissions of HIV-infected patients to an intensive care unit. HIV Med. Apr 2006;7(3):193-196. Available at http://www.ncbi.nlm.nih.gov/pubmed/16494634.
- Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis. Mar 15 2011;52(6):793-800. Available at http://www.ncbi.nlm.nih.gov/pubmed/21367734.
- Greenberg AE, Hader SL, Masur H, Young AT, Skillicorn J, Dieffenbach CW. Fighting HIV/AIDS in Washington, D.C. Health affairs. Nov-Dec 2009;28(6):1677-1687. Available at http://www.ncbi.nlm.nih.gov/pubmed/19887408.
- Gebo KA, Fleishman JA, Reilly ED, Moore RD, Network HIVR. High rates of primary Mycobacterium avium complex and Pneumocystis jiroveci prophylaxis in the United States. Medical care. Sep 2005;43(9 Suppl):III23-30. Available at http://www.ncbi.nlm.nih.gov/pubmed/16116306.
- Bonnet F, Lewden C, May T, et al. Opportunistic infections as causes of death in HIV-infected patients in the HAART era in France. Scandinavian journal of infectious diseases. 2005;37(6-7):482-487. Available at http://www.ncbi.nlm.nih.gov/pubmed/16089023.
- Teshale EH, Hanson DL, Wolfe MI, et al. 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. Mar 15 2007;44(6):879-883. Available at http://www.ncbi.nlm.nih.gov/pubmed/17304464.
- Gebo KA, Fleishman JA, Moore RD. Hospitalizations for metabolic conditions, opportunistic infections, and injection drug use among HIV patients: trends between 1996 and 2000 in 12 states. J Acquir Immune Defic Syndr. Dec 15 2005;40(5):609-616. Available at http://www.ncbi.nlm.nih.gov/pubmed/16284539.
- Betz ME, Gebo KA, Barber E, et al. Patterns of diagnoses in hospital admissions in a multistate cohort of HIV-positive adults in 2001. Medical care. Sep 2005;43(9 Suppl):III3-14. Available at http://www.ncbi.nlm.nih.gov/pubmed/16116304.
- Moorman AC, Buchacz K, Richardson JT, al. e. Temporal trends in hospitalizations and hospital-associated diagnoses in the HIV Outpatient Study (HOPS) 1994-2002. In: XVI International AIDS Conference; August 13-18, 2006; Toronto, Canada. Abstract MOPE0071.
- Louie JK, Hsu LC, Osmond DH, Katz MH, Schwarcz SK. Trends in causes of death among persons with acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy, San Francisco, 1994-1998. J Infect Dis. Oct 1 2002;186(7):1023-1027. Available at http://www.ncbi.nlm.nih.gov/pubmed/12232845.
- Palella FJ, Jr., Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. Sep 2006;43(1):27-34. Available at http://www.ncbi.nlm.nih.gov/pubmed/16878047.
- Smit C, Geskus R, Walker S, et al. Effective therapy has altered the spectrum of cause-specific mortality following HIV seroconversion. AIDS. Mar 21 2006;20(5):741-749. Available at http://www.ncbi.nlm.nih.gov/pubmed/16514305.
- Buchacz K, Baker RK, Moorman AC, et al. Rates of hospitalizations and associated diagnoses in a large multisite cohort of HIV patients in the United States, 1994-2005. AIDS. Jul 11 2008;22(11):1345-1354. Available at http://www.ncbi.nlm.nih.gov/pubmed/18580614.
- Buchacz K, Baker RK, Palella FJ, Jr., et al. AIDS-defining opportunistic illnesses in US patients, 1994-2007: a cohort study. AIDS. Jun 19 2010;24(10):1549-1559. Available at http://www.ncbi.nlm.nih.gov/pubmed/20502317.
- Lawn SD, Butera ST, Folks TM. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev. Oct 2001;14(4):753-777, table of contents. Available at http://www.ncbi.nlm.nih.gov/pubmed/11585784.
- Toossi Z, Mayanja-Kizza H, Hirsch CS, et al. Impact of tuberculosis (TB) on HIV-1 activity in dually infected patients. Clinical and experimental immunology. Feb 2001;123(2):233-238. Available at http://www.ncbi.nlm.nih.gov/pubmed/11207653.
- Sadiq ST, McSorley J, Copas AJ, et al. The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen. Sexually transmitted infections. Oct 2005;81(5):380-385. Available at http://www.ncbi.nlm.nih.gov/pubmed/16199736.
- Bentwich Z. Concurrent infections that rise the HIV viral load. Journal of HIV Therapy. Aug 2003;8(3):72-75. Available at http://www.ncbi.nlm.nih.gov/pubmed/12951545.
- Kublin JG, Patnaik P, Jere CS, et al. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet. Jan 15-21 2005;365(9455):233-240. Available at http://www.ncbi.nlm.nih.gov/pubmed/15652606.
- Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science. Dec 8 2006;314(5805):1603-1606. Available at http://www.ncbi.nlm.nih.gov/pubmed/17158329.
- Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. Mar 30 2000;342(13):921-929. Available at http://www.ncbi.nlm.nih.gov/pubmed/10738050.
- DiRienzo AG, van Der Horst C, Finkelstein DM, Frame P, Bozzette SA, Tashima KT. Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. AIDS research and human retroviruses. Jan 20 2002;18(2):89-94. Available at http://www.ncbi.nlm.nih.gov/pubmed/11839141.
- Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial. Lancet. May 1 1999;353(9163):1469-1475. Available at http://www.ncbi.nlm.nih.gov/pubmed/10232312.
- Whalen CC, Johnson JL, Okwera A, et al. A trial of three regimens to prevent tuberculosis in Ugandan adults infected with the human immunodeficiency virus. Uganda-Case Western Reserve University Research Collaboration. N Engl J Med. Sep 18 1997;337(12):801-808. Available at http://www.ncbi.nlm.nih.gov/pubmed/9295239.
- Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial. Cotrimo-CI Study Group. Lancet. May 1 1999;353(9163):1463-1468. Available at http://www.ncbi.nlm.nih.gov/pubmed/10232311.
- Chintu C, Bhat GJ, Walker AS, et al. Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Lancet. Nov 20-26 2004;364(9448):1865-1871. Available at http://www.ncbi.nlm.nih.gov/pubmed/15555666.
- Centers for Disease C. Guidelines for prophylaxis against Pneumocystis carinii pneumonia for persons infected with human immunodeficiency virus. MMWR Morb Mortal Wkly Rep. Jun 16 1989;38 Suppl 5(Suppl 5):1-9. Available at http://www.ncbi.nlm.nih.gov/pubmed/2524643.
- Masur H. Recommendations on prophylaxis and therapy for disseminated Mycobacterium avium complex disease in patients infected with the human immunodeficiency virus. Public Health Service Task Force on Prophylaxis and Therapy for Mycobacterium avium Complex. N Engl J Med. Sep 16 1993;329(12):898-904. Available at http://www.ncbi.nlm.nih.gov/pubmed/8395019.
- USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. MMWR Recomm Rep. Jul 14 1995;44(RR-8):1-34. Available at http://www.ncbi.nlm.nih.gov/pubmed/7565547.
- 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. USPHS/IDSA Prevention of Opportunistic Infections Working Group. MMWR Recomm Rep. Jun 27 1997;46(RR-12):1-46. Available at http://www.ncbi.nlm.nih.gov/pubmed/9214702.
- 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. U.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA). MMWR Recomm Rep. Aug 20 1999;48(RR-10):1-59, 61-56. Available at http://www.ncbi.nlm.nih.gov/pubmed/10499670.
- Kaplan JE, Masur H, Holmes KK, Usphs, Infectious Disease Society of A. Guidelines for preventing opportunistic infections among HIV-infected persons--2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. Jun 14 2002;51(RR-8):1-52. Available at http://www.ncbi.nlm.nih.gov/pubmed/12081007.
- USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group. Clin Infect Dis. Aug 1995;21 Suppl 1:S32-43. Available at http://www.ncbi.nlm.nih.gov/pubmed/8547510.
- 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: disease-specific recommendations. USPHS/IDSA Prevention of Opportunistic Infections Working Group. US Public Health Services/Infectious Diseases Society of America. Clin Infect Dis. Oct 1997;25 Suppl 3:S313-335. Available at http://www.ncbi.nlm.nih.gov/pubmed/9356832.
- 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Clin Infect Dis. Apr 2000;30 Suppl 1:S29-65. Available at http://www.ncbi.nlm.nih.gov/pubmed/10770913.
- USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. Ann Intern Med. Feb 1 1996;124(3):349-368. Available at http://www.ncbi.nlm.nih.gov/pubmed/8554235.
- 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Ann Intern Med. Nov 15 1997;127(10):922-946. Available at http://www.ncbi.nlm.nih.gov/pubmed/9382373.
- 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with HIV: Part I. Prevention of exposure. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention. American family physician. Sep 1 1997;56(3):823-834. Available at http://www.ncbi.nlm.nih.gov/pubmed/9301575.
- 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with HIV: part I. Prevention of exposure. American family physician. Jan 1 2000;61(1):163-174. Available at http://www.ncbi.nlm.nih.gov/pubmed/10643957.
- Antiretroviral therapy and medical management of pediatric HIV infection and 1997 USPHS/IDSA report on the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Pediatrics. Oct 1998;102(4 Pt 2):999-1085. Available at http://www.ncbi.nlm.nih.gov/pubmed/9826994.
- Kaplan JE, Masur H, Jaffe HW, Holmes KK. Preventing opportunistic infections in persons infected with HIV: 1997 guidelines. JAMA. Jul 23-30 1997;278(4):337-338. Available at http://www.ncbi.nlm.nih.gov/pubmed/9228443.
- Brooks JT, Kaplan JE, Masur H. What's new in the 2009 US guidelines for prevention and treatment of opportunistic infections among adults and adolescents with HIV? Top HIV Med. Jul-Aug 2009;17(3):109-114. Available at http://www.ncbi.nlm.nih.gov/pubmed/19675369.
- Benson CA, Kaplan JE, 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. MMWR Recomm Rep. Dec 17 2004;53(RR-15):1-112. Available at http://www.ncbi.nlm.nih.gov/pubmed/15841069.
- Mofenson LM, Oleske J, Serchuck L, et al. Treating opportunistic infections among HIV-exposed and infected children: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. MMWR Recomm Rep. Dec 3 2004;53(RR-14):1-92. Available at http://www.ncbi.nlm.nih.gov/pubmed/15577752.
- Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. Apr 10 2009;58(RR-4):1-207; quiz CE201-204. Available at http://www.ncbi.nlm.nih.gov/pubmed/19357635.
- Mofenson LM, Brady MT, Danner SP, et al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. Sep 4 2009;58(RR-11):1-166. Available at http://www.ncbi.nlm.nih.gov/pubmed/19730409.
- Cruickshank DP, Wigton TR, Hays PM. Maternal physiology in pregnancy. In: Gabbe SG, Neibyl JR, Simpson JL, eds. Obstetrics: Normal and Problem Pregnancies. New York, NY: Churchchill Livingstone, 1996.
- ACOG Committee on Obstetric Practice. ACOG Committee Opinion. Number 299, September 2004 (replaces No. 158, September 1995). Guidelines for diagnostic imaging during pregnancy. Obstet Gynecol. Sep 2004;104(3):647-651. Available at http://www.ncbi.nlm.nih.gov/pubmed/15339791.
- Toppenberg KS, Hill DA, Miller DP. Safety of radiographic imaging during pregnancy. American family physician. Apr 1 1999;59(7):1813-1818, 1820. Available at http://www.ncbi.nlm.nih.gov/pubmed/10208701.
- Adelstein SJ. Administered radionuclides in pregnancy. Teratology. Apr 1999;59(4):236-239. Available at http://www.ncbi.nlm.nih.gov/pubmed/10331526.