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.
Prevention of opportunistic infections in HIV is a multistep approach which includes the following:
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.
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.
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
Many different pathogens have been associated with the development of IRIS. The following are the leading pathogens:
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.
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.
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