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Prevention of Opportunistic Infections (OIs) in Those With HIV Infection

December 2001

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Prior to the availability of effective antiretroviral therapy (ART), most patients with HIV infection could expect to experience a fairly predictable and inexorable decline in their CD4 count. Once a patient's CD4 count declines significantly, prophylaxis for opportunistic infections is initiated and continues indefinitely.

Beginning in 1995, the availability of more effective protease inhibitor-based ART forever altered this algorithm. With more potent ART, many patients experience significant and sustained improvements in immunologic function as evidenced by CD4 count increases and in vitro responses to antigenic stimulation. Soon the question arose whether those who, during CD4 nadir, met criteria for prophylaxis still required such agents after experiencing ART-induced immune reconstitution.

Initial anecdotal reports gave way to longer observational trials. When last reviewed in HEPP News1, some data existed that supported stopping primary and secondary prophylaxis in the setting of sustained ART-induced CD4 count increases. Subsequently, further information has accumulated that has now led to a revision in the United States Public Health Services/Infectious Diseases Society of America (USPHS/IDSA) Guidelines for the Prevention of Opportunistic Infections in HIV-Infected Adults and Adolescents. The revised version of these recommendations, released November 28, 2001, is available at www.HIVATIS.org/trtgdlns.html. Some important aspects of these guidelines will be summarized here.


Initiating Primary Prophylaxis to Prevent OIs

The recommendations for prevention of disease related to Pneumocystis carinii, Mycobacterium tuberculosis, Mycobacterium avium complex, Toxoplasma gondii, Streptococcus pneumonia, Hepatitis A and B, influenza, and Varicella are available and have not significantly changed from the prior guidelines. Some are summarized in Table 1.

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Table 1: Opportunistic Infection Prophylaxis to Prevent First Infection
(Strongly Recommended Standard of Care)2
PathogenIndicationFirst Choice Preventive RegimenAlternative Preventive Regimen
Pneumocystis cariniiCD4+ count <200/µL or oropharyngeal candadiasisTrimethoprim- sulfamethoxazole (TMP-SMZ) 1 DS or SS po qd (AI)Dapsone 50 mg po bid or 100mg po qd (BI); dapsone 50 mg po qd plus pyrimethamine 50 mg po qw plus leucovorin 25 mg po qw (BI); dapsone 200 mg po plus pyrimethamine 75 mg po plus leucovorin 25 mg po qw (BI); aerosolized pentamidine 300 mg q month via Respirgard II nebulizer (BI); atovaquone 1500 mg po qd (BI); TMP-SMZ 1 DS po tiw (BI)
Toxoplasma gondiiIgG antibody to Toxoplasma and CD4+ count <100/µLTMP-SMZ 1 DS po qd (AII)TMP-SMZ 1 SS po qd (BIII); dapsone 50 mg po qd plus pyrimethamine 50 mg po qd plus leucovorin 25 mg po qw (BI); atovaquone 1500 mg po qd with or without pyrimethamine 25 mg po qd plus leucovorin 10 mg po qd (CIII)
Mycobacterium avium complexCD4+ count <50/µLAzithromycin** 1200 mg po qw (AI), or clarithromycin 500 mg po bid (AI)Rifabutin 300 mg po qd (CI); azithromycin 1200 mg po qw plus rifabutin 300 mg po qd
Varicella zoster virus (VZV)Significant exposure to chicken pox or shingles for patients who have no history of either condition, or, if available, negative antibody to VZVVaricella zoster immune globulin (VZIG) 5 vials (1.25 mL each) im, administered <96 h after exposure, ideally within 48 h (AIII)Ratings:

A. Should always be offered

B. Should generally be offered

C. Optional

D. Should generally NOT be offered

E. Should NEVER be offered

Quality of Evidence
  1. Evidence from at least one properly randomized, controlled trial.

  2. Evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from more than one center), or from multiple time-series studies. Or dramatic results from uncontrolled experiments.

  3. Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.


Initiating Secondary Prophylaxis To Prevent OIs

After treatment of active disease, secondary prophylaxis is recommended to prevent relapse of many common OIs. These recommendations are also not significantly changed from prior USPHS/IDSA recommendations and are summarized in Table 2.


Table 2: Prophylaxis to Prevent Recurrence of Opportunistic Disease in Adults (Secondary Prophylaxis)
PathogenFirst Choice Preventive RegimenAlternative Preventive Regimens
Pneumocystis cariniisame as primary prophylaxis; see Table 1
Toxoplasma gondiisame as primary prophylaxis; see Table 1
Mycobacterium avium complexClarithromycin** 500 mg po bid (AI) plus ethambutol 15 mg/kg po qd (AII); + rifabutin 300 mg po qd (CI)Azithromycin 500 mg po qd (AII) plus ethambutol 15 mg/kg po qd; + 300 mg po qd (CI)
CytomegalovirusGanciclovir 5-6 mg/kg/day iv 5-7 days/wk or 1000 mg po tid (AI); foscarnet 90-120 mg/kg iv qd (AI); (for retinitis) ganciclovir sustained-release implant q 6-9 mo plus ganciclovir 1.0-1.5 g po tod (AI)Cidofovir 5 mg/kg iv qow + probenecid 2 g po 3 h before the dose followed by 1 g po 2 h after the dose and 1 g po 8 h after the dose (total of 4 g) (AI); fomivirsen 1 vial (330 mg) injected into the vitreous then repeated every 2-4 wks (AI); valganciclovir 900 mg po qd (BI)


Criteria For Discontinuing Primary and Secondary Prophylaxis

For many of the most common OIs, data exists to support the discontinuation of secondary prophylaxis in those with sustained ART-induced immunologic recovery. Such an approach carries the potential for decreasing the potential for side effects, drug-drug interactions, total pill burden, and the significant costs associated with some prophylactic medications. (Per annum costs: clarithromycin 500 mg bid $2,843; fluconazole 200 mg qd $4,603; ganciclovir 1,000 mg tid $17,794.) Table 3 details updated recommendations for starting, discontinuing, and restarting primary and secondary prophylaxis for some of the most devastating HIV associated opportunistic infections. For many OIs, the evidence for efficacy of continued prophylaxis might not outweigh the potential adverse consequences.

Each patient must be approached on an individualized basis. Discontinuing prophylaxis carries some risk for those patients who will not have access to frequent medical evaluation and blood test monitoring. In some such cases it may be most prudent to continue prophylaxis until such time as the patient can be monitored more closely.

For patients who can be followed closely, data support discontinuing primary prophylaxis in those whose CD4 count in response to ART has for at least 3 months remained >100 (Mycobacterium avium complex) or >200 (Pneumocystis, Toxoplasmosis).

For patients who have experienced active disease due to Pneumocystis, Toxoplasma, Mycobacterium avium, Cryptococcus, and Cytomegalovirus, criteria are provided for the discontinuing of secondary prophylaxis (see Table 3). Again, this should be undertaken on an individualized basis and only after the patient is educated about the risks and benefits involved with each approach. For some patients, the ability to be rewarded for good ART adherence by stopping prophylactic medications may serve as an additional incentive to continue to comply with ART.


Table 3: Guidelines for Discontinuing and Restarting Primary and Secondary Prophylaxis for Opportunistic Infections2
Opportunistic InfectionIndications for Discontinuing 10 ProphylaxisIndications for Restarting 10 ProphylaxisIndications for Discontinuing 20 Prophylaxis*Indications for Restarting 20 Prophylaxis
Pneumocystis carinii PneumoniaCD4+ >200 cells/µL for >3 months (AI)CD4+ <200 cells/µL (AIII)CD4+ >200 cells/µL for >3 months (BII)CD4+ <200 cells/µL (AIII)
ToxoplasmaCD4+ >200 cells/µL for >3 months (AI)CD4+ <100-200 cells/µL (AIII)CD4+ >200 cells/µL sustained (>6 mo) and completed initial therapy and asymptomatic for toxo (CIII)CD4+ <200 cells/µL (AIII)
Mycobacterium avium complexCD4+ >100 cells/µL for >3 months (AI)CD4+ <50-100 cells/µL (AIII)CD4+ >100 cells/µL sustained (>6 mo) and completed 12 mo of MAC therapy and asymptomatic for MAC (CIII)CD4+ <100 cells/µL (AIII)
Cytomegalovirus retinitisNot applicableNot applicableCD4+ >100-150 cells/µL sustained (>6 mo) and no evidence of active disease and regular opthalmic examination (BII)CD4+ <100-150 cells/µL (AIII)
CryptococcosisNot applicableNot applicableCD4+ >100-200 cells/µL sustained (6 mo) and completed initial therapy and asymptomatic for Cryptococcosis (CIII)CD4+ <100-200 cells/µL (AIII)
* After active disease.


Risk Avoidance: Sexual and Injection Drug Exposures

Recommendations intended to help HIV-infected individuals avoid exposure to or infection with opportunistic infections are provided and categorized by risk group. Clearly, at least some prisoners will continue to be sexually active while incarcerated and some will engage in injection drug use (IDU). In spite of the fact that both activities are prohibited in correctional facilities, patients need more educational information than "just say no." Sexual and IDU abstinence is the safest option for those interested in reducing the risk for acquisition of CMV, HSV, HPV, HHV8, other HIV strains, HAV, HBV, HCV and a variety of other enteric pathogens. Acknowledging that risk behaviors continue during incarceration, prisoners should be provided harm reduction educational information detailing how to decrease health risks if they choose to continue to be sexually active and/or engage in IDU. Patients should be instructed about which sexual practices carry the greatest health risks to them and their partners. To decrease the risk for enteric infections such as cryptosporidium, salmonella, shigella, campylobacter, amebiasis, giardiasis, and hepatitis A, patients should avoid sexual practices that might result in oral exposure to feces. All non-immune prisoners should be offered vaccination for hepatitis B. Non-immune IDUs and men who have sex with men should be offered vaccination for hepatitis A. In those systems in which they are available, prisoners should use latex condoms during every act of sexual intercourse. [As this issue of HEPP News went to press, the Los Angeles county jail joined a handful of correctional facilities in this country that make condoms available to prisoners].

Prisoners with a history of IDU should be provided substance abuse treatment, and linked to community services at the time of parole. Recognizing the reality that many individuals will relapse to IDU during or following incarceration, patients should be educated to never share or reuse syringes, needles, or drug preparation equipment. Those who will be reusing injection equipment should be advised to clean all materials with bleach and water. Furthermore, inmates should be educated on syringe availability and encouraged to use services such as pharmacy purchase and needle exchange where available, and to explore the possibility of physician prescription when other services are not available.3 Non-immune IDUs should be vaccinated for hepatitis A and B.


Risk Avoidance: Occupational Exposures

HIV-infected prisoners do hold jobs while incarcerated that can place them at risk for significant OIs. Those working in sanitation, janitorial or laundry positions can come into contact with body wastes, contaminated sharps, and other materials that can transmit diseases. All such workers should be provided personal protective equipment and educated in its use. All non-immune workers should be offered vaccination against hepatitis A and B. As a rule, prisoners should not be involved in direct patient care. In those systems that allow such work, inmate workers should be provided hepatitis B vaccination.

In areas endemic for histoplasmosis, HIV-infected prisoners should avoid activities that are associated with an increased risk for infection with this organism. Examples include cleaning or remodeling old buildings, disturbing the soil beneath bird roosting sites, and cleaning chicken coops. Similarly, in areas endemic for coccidioidomycosis, patients should avoid extensive exposure to disturbed native soil as might occur during agricultural work or building excavation.


Risk Avoidance: Food Related Exposures

Prisoners commonly store food in their cells, and rarely have access to refrigeration or a way to reheat leftovers. Patients should be warned about the risks associated with eating food that has been improperly stored or cooked. Prisoners may receive food during visits or in packages from home. Soft cheeses such as Mexican style queso fresco carry a risk for listeriosis and should be avoided by those who are HIV infected.

Correctional staff should routinely monitor the facility's kitchen practices to ensure that all meat and poultry are appropriately cooked (to an internal temperature of 180° for poultry, and 165° for meat.) All produce should be washed, and procedures should be in place to ensure that uncooked meat and poultry does not come into contact with other foods. All counters, cutting boards, knives, and utensils should be thoroughly cleaned after being used to prepare uncooked meat, poultry, and fish. Although there is no medical justification for the exclusion of those with HIV, hepatitis B, or hepatitis C from working in food service, those with diarrhea, open lesions on their hands or arms, or acute hepatitis A should not work as food handlers. Providers may consult the NCCHC guidelines, including "P-16: Kitchen Sanitation and Food Handlers" for further recommendations.


Conclusion

In conclusion, HIV-infected prisoners are at significant risk for a wide variety of OIs. Information exists which can assist our patients to avoid exposure to and infection with many of these organisms. Through patient education and the appropriate use of immunizations, morbidity and mortality due to OIs can be avoided. Data are also accumulating to support the discontinuation of OI prophylaxis in those who have experienced ART-induced immunologic recovery. The USPHS/IDSA guidelines provide guidance to clinicians and patients who are considering withdrawing preventive therapy for the most common OIs.


* Nothing to disclose.

** During pregnancy, azithromycin is recommended instead of clarithromycin due to the teratogenicity of clarithromycin in animals.


References

  1. "Prevention of Opportunistic Infections." HIV 101, HEPP News. 2000 October.

  2. 2001 USPHS/IDSA Guidelines for the Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus. On the Web at http://www.hivatis.org/guidelines/other/OIs/OIGNov27.pdf.

  3. Burris et al. Ann Intern Med. 2000;133:218-226.


Back to the HEPP News December 2001 contents page.

A note from TheBody.com: Since this article was written, the HIV pandemic has changed, as has our understanding of HIV/AIDS and its treatment. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!



  
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This article was provided by Brown Medical School. It is a part of the publication HEPP News.
 
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