HIV, Prevention Of Opportunistic Infections

Article Author:
Usama Sadiq
Article Editor:
Nilmarie Guzman
Updated:
10/27/2018 12:31:37 PM
PubMed Link:
HIV, Prevention Of Opportunistic Infections

Introduction

Opportunistic infections (OI) are infections that occur as a result of significant decline in patient's immune system. These remain a major cause of morbidity and mortality in HIV positive individuals. Risk of opportunistic infection increases when patient's CD4 count decline under 200 cells.  Some opportunistic infections can occur in the setting of higher CD4 count. Even though the introduction of HAART in 1995 decreased significant the morbidity and mortality associated with HIV and opportunistic infections, these do occur in a percentage of patients. 

Function

Prevention of opportunistic infections in HIV is a multistep approach which includes the following:

  • Antiretroviral therapy improves CD4 counts significantly and is the most effective measure in preventing opportunistic infections.
  • Vaccination is an effective measure in preventing some specific infections and diseases in HIV patients, including the following:
  1. HAV
  2. HBV
  3. HPV
  4. Sequential PCV 13 and PPSV23
  5. Influenza
  6. TdaP
  7. H. influenza
  8. PolioKeep in mind that only killed vaccines should be used in patients with HIV who have CD4 counts less than 200. If the counts are higher, live vaccines like MMR can be administered. 
  • Avoiding certain exposures, to prevent primary infection, for example:
  1. Toxoplasmagondii avoid cat litter and undercooked meat.
  2. Tuberculosis- avoid contact with a patient with tuberculosis (TB).
  3. Cryptococcus- avoid bird exposure like pigeons. 
  • Antimicrobial therapy, usually directed against specific organisms, is started in addition to HAART. It is not used in the following conditions:
  1. Low disease incidence
  2. High risk of developing drug resistance
  3. High adverse-effect profile and fatal drug reactionsAntimicrobial therapy can be used in a variety of settings such as the following:
  1. Preventing infection in uninfected individuals, e.g., P. jiroveci
  2. Preventing infections by dormant body microbes, e.g. T. gondi
  3. Treating asymptomatic patients who have positive serology, e.g., C. immitis

Role of CD4 Count Testing

Certain infections show the full effect when the CD4 count falls below a critical threshold. Therefore, CD4 counts play a vital role in started targeted prophylaxis.

  1. ALL CD4 counts: All HIV patients regardless of CD4 counts should be screened for latent TB using interferon assays or tuberculin testing.
  2. CD4250 cells/microL: Annual IgG and IgM assays against coccidiomycosis. Patients with positive serology can be given systemic azole antifungal therapy with fluconazole or itraconazole and discontinued when CD4 count remains above 250 for at least 6 months. 
  3. CD4 less than 00: Start prophylaxis against Pneumocystis jiroveci using TMP-SMX. For patients with sulfa allergy, use pentamidine. 
  4. CD4 less than 150: Itraconazole should be used to prevent Histoplasma infection ONLY in patients who live in endemic areas. 
  5. CD4 less than 100: Administer suppressive therapy with Trimethoprim/sulfamethoxazole (TMP/SMX) to prevent reactivation of T. gondii in patients with a CD4 count less than or equal to 100 cells/microL and a positive toxoplasmosis IgG serology. For patients who have contraindications to TMP-SMX, use dapsone plus pyrimethamine and leucovorin. If the patient is intolerant or allergic to the above two regimens, administer atovaquone without pyrimethamine/leucovorin. Monotherapy with dapsone, pyrimethamine, azithromycin, clarithromycin should not be used. Patients receiving antiretroviral therapy can discontinue suppressive therapy when the CD4 count is more than 200 for at least 3 months.
  6. CD4 counts less than 50: For patients who are initiating antiretroviral therapy (ART), do not routinely administer antimicrobial prophylaxis to prevent infection with Mycobacterium avium complex (MAC). Although MAC prophylaxis with a macrolide had been common practice for all patients with a CD4 count less than 50 cells/microL prior to the introduction of effective ART, the approach has changed since the risk of MAC infection is low in the setting of ART, the outcome of MAC disease does not differ among those individuals who did or did not receive prophylaxis, and there are no clinical trial data on MAC prophylaxis in the era of effective ART. Furthermore, some patients may have an asymptomatic infection with MAC that becomes evident after starting ART due to an immune reconstitution inflammatory syndrome. In this setting, if single-drug therapy with azithromycin was used for prophylaxis, it might select for macrolide drug resistance.

    However, on rare occasion, there can be a temporary delay in initiating ART among those with a CD4 count less than 50 cells/microL (e.g., patient refusal). Unless there are concerns that the patient may have active MAC infection (e.g., fevers, weight loss), MAC prophylaxis should be initiated and continued until ART is started. If there is a concern for active infection, a mycobacterial blood culture should first be obtained, and prophylaxis should be delayed for 7 to 10 days, pending the results. A more detailed discussion of MAC prophylaxis is presented elsewhere.

Issues of Concern

The term "immune reconstitution inflammatory syndrome" (IRIS) describes a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes following the initiation of antiretroviral therapy (ART) in HIV-infected individuals. Preexisting infections in individuals with IRIS may have been previously diagnosed and treated, or they may be subclinical and unmasked by the host's regained capacity to mount an inflammatory response.

If immune function improves rapidly following the commencement of ART, systemic or local inflammatory reactions may occur at the site(s) of the preexisting infection. This inflammatory reaction is usually self-limited, especially if the preexisting infection is effectively treated. Rarely, long-term sequelae and fatal outcomes may occur, particularly when neurologic structures are involved.

Diagnostic Criteria for IRIS

  • Presence of AIDS with a low pretreatment CD4 count (often less than 100 cells/microL). One important exception to this general rule is tuberculosis. IRIS secondary to preexisting M. tuberculosis infection may occur in individuals with CD4 counts greater than 200 cells/microL.
  • Positive virologic and immunological response to antiretroviral therapy (ART).
  • No evidence of drug-resistant infection, bacterial superinfection, drug allergy or other adverse drug reactions. Patient noncompliance or reduced drug levels due to drug-drug interactions or malabsorption after appropriate evaluation for the clinical presentation.
  • Presence of clinical manifestations consistent with an inflammatory condition.
  • Temporal association between ART initiation and the onset of clinical features of the illness.

Many different pathogens have been associated with the development of IRIS. The following are the leading pathogens:

  1. Mycobacterium tuberculosis
  2. Mycobacterium avium complex
  3. Cytomegalovirus
  4. Cryptococcus neoformans
  5. Pneumocystis jirovecii
  6. Herpes simplex virus
  7. Hepatitis B virus
  8. Human herpesvirus 8 (associated with Kaposi sarcoma)

Several studies have demonstrated that lower CD4 cell counts or high HIV RNA at the time of treatment initiation increase the risk of developing IRIS. Response to ART also plays an important role in predicting risk.

Clinical Significance

The bottom line comes down to the fact that HIV itself is not responsible for the mortality of patients but the opportunistic infections that it allows to take over the immunocompromised host. Up to 2 million patients are affected by HIV yearly worldwide. As there is no vaccine for HIV, behavioral and biomedical prevention strategies are in place to avoid infection altogether and reduce the incidence of opportunistic infections.