The Changing Nature of the Prevention and Management of Opportunistic Infections
Total Page:16
File Type:pdf, Size:1020Kb
Perspective - Opportunistic Infections Volume 10 Issue 5 November/December 2002 Perspective The Changing Nature of the Prevention and Management of Opportunistic Infections As related by Henry Masur, MD, at the A second explanation for the oping PCP within 6 months of a medical International AIDS Society–USA CME absence of continued decline in oppor- visit, one quarter had a CD4+ cell count course in Washington, DC, in May 2002, tunistic infection rates is the continued greater than 200/µL. Thus clinicians opportunistic infection rates have spread and progression of HIV disease should keep in mind that the “thresh- declined since the advent of potent in patient groups that are not receiving olds” published for opportunistic infec- antiretroviral therapy. However, there adequate medical care. In some sites in tions are general guidelines, not abso- is evidence to indicate that these Washington, DC, for example, many lute boundaries of susceptibility. Both declines have stalled and perhaps patients are now presenting with oppor- prior to the era of potent antiretroviral reversed in some populations in associ- tunistic infections as the initial manifes- therapy and currently, opportunistic ation with long-term antiretroviral fail- tation of HIV disease. Adult/Adolescent infections will occasionally occur at ure and inadequate access to care. Spectrum of HIV Disease Project data on unusually high CD4+ cell counts. 2365 patients developing Pneumocystis There are data to indicate that the The use of chemoprophylaxis for oppor- carinii pneumonia (PCP) from 1996 CD4+ cell count nadir reached prior to tunistic infections and the advent and through 1999 indicate that 45% were not restoration of CD4+ counts to greater widespread use of potent antiretroviral in care at the time they developed PCP, than 200 cells/µL is not predictive of therapy were associated with a marked compared with 41% of 3863 patients increased risk for opportunistic infec- decline in rates of most opportunistic who developed PCP from 1993 through tions. As shown in a study by Miller and infections in HIV-infected individuals 1996. The proportion of patients devel- from the early 1990s through 1997. oping PCP who were in care and met the However, a recent report from the criteria for PCP prophylaxis but received Adult/Adolescent Spectrum of Disease no prophylaxis was 6% in the period Many patients are now Project indicates that additional reduc- from 1993 to 1996, and increased to 14% tions in rates for many opportunistic in 1996 to 1999. A large proportion of presenting with infections were not observed between patients developing PCP were in care 1997 and 1999 (McNaghten et al, 39th and met criteria for and received PCP opportunistic infections IDSA, 2001). One explanation for these prophylaxis, but developed PCP because observations is that more patients are of nonadherence or resistance to pro- as the initial experiencing immunologic decline in phylactic regimens. A smaller propor- association with long-term virologic fail- tion of patients continue to develop PCP manifestation of ure of antiretroviral therapy. An optimal at CD4+ cell counts higher than the level virologic response (ie, viral suppression established as the criterion for institu- HIV disease to below limits of assay detection) is not tion of primary PCP prophylaxis, which achieved in many patients with initial or is 200/µL or less. subsequent treatment. Continued viro- logic failure places such patients at Opportunistic Infection Risk colleagues (Ann Intern Med, 1999), oppor- increased risk of disease progression. and Prophylaxis tunistic infection incidence rates and For example, a 2000 review of 20 potent 95% confidence intervals in patients therapy arms in antiretroviral treatment CD4+ cell count still appears to be a reli- with CD4+ count nadirs of less than 200, studies (Bartlett et al, AIDS, 2001) indi- able predictor of risk for opportunistic 150, 100, or 50 cells/µL did not differ cated that, on intent-to-treat analysis in infections in the potent antiretroviral substantially (incidence rates of 3.7-8.1 the majority of the study arms, 50% or therapy era. In terms of heightening per 100 patient-years) when cell counts less of patients achieved plasma HIV-1 diagnostic vigilance for opportunistic increased to greater than 200/µL on RNA levels less than 50 copies/mL at 48 infections, however, it has long been potent therapy. However, the incidence weeks. An increased incidence of oppor- recognized that risk extends to patients rate was dramatically elevated to 72.9 tunistic infections during virologic fail- with CD4+ cell counts above the levels per 100 patient-years in patients with ure is not currently supported in the established as threshold levels for initi- persistently low CD4+ cell counts published literature, however. ation of prophylactic therapy. For exam- (Figure 1). ple, data from the Multicenter AIDS These and other data indicating that Dr Masur is Chief of the Critical Care Cohort study (Phair et al, N Engl J Med, CD4+ cell count increases on potent Medicine Department of the National 1990) prior to the advent of potent ther- antiretroviral therapy are associated Institutes of Health in Bethesda, Md. apy showed that among patients devel- with reduced risk for opportunistic infec- 27 International AIDS Society–USA Topics in HIV Medicine tions have led to recommendations for discontinuation of prophylaxis based on CD4+ cell count and adequate control of plasma HIV-1 RNA level. Currently, there are specific CD4+ cell count-based Incidence Rate/ 200 Nadir CD4+ of 100 Patient-Years guidelines for discontinuation of prima- L) Responders (95% Cl) µ ry prophylaxis for PCP, toxoplasmosis, µ 150 <200/ L 3.7 (3.3–4.1) and Mycobacterium avium complex (MAC) <150/µL 6.0 (3.4–10.0) infection and secondary prophylaxis for <100/µL 8.1 (4.5–13.4) these infections and for cytomegalovirus 100 <50/µL 5.9 (3.0–10.2) (CMV) disease and cryptococcosis Nonresponders 72.9 (69.0–76.8) (USPHS/IDSA, 2001). Data are currently with Persistent CD4+ Count (cells/ 50 insufficient to recommend discontinua- Low CD4+ tion of secondary prophylaxis for histo- plasmosis or coccidioidomycosis based 0 on CD4+ cell count. However, many Time practitioners with considerable experi- ence with these latter types of infections are of the opinion that discontinuation Figure 1. Effect of pretreatment nadir CD4+ cell count on incidence of opportunistic infec- of prophylaxis is safe with sufficient tions in patients whose CD4+ cell count increased to greater than 200/µL on potent CD4+ cell count increase on potent antiretroviral therapy (responders) and incidence in patients with persistently low cell count antiretroviral therapy. (nonresponders). Adapted with permission from Miller et al, Ann Intern Med, 1999. HIV-Associated Pulmonary Disease same consult service from 1997 to 2000 lavage and immunofluorescence stain- indicate that manifestations were due to ing. In practiced hands, diagnosis can be Pulmonary disease remains one of the PCP in 9 (18%), other bacterial infection made in a high percentage of cases using most common infectious complications in 24 (47%), CMV in 2 (4%), and lym- induced sputum and immunofluores- encountered in patients with HIV dis- phoma in 8 (16%; Wolff and O’Donnell, cence. There is considerable interest in ease. PCP, tuberculosis, and pneumo- Chest, 2001). However, the types of polymerase chain reaction (PCR)-based coccal and Haemophilus infections remain opportunistic infections observed may diagnostic techniques for PCP. One common among pulmonary infections, depend on the patient populations recent study showed that PCR analysis of as does infection due to atypical and studied. As noted, experience at some simple oral washes was associated with viral pathogens. Less common causes of centers indicates that many HIV-infected 91% sensitivity, 94% specificity, 76% pos- disease include histoplasmosis and coc- individuals without adequate connec- itive predictive value, and 98% negative cidioidomycosis, toxoplasmosis, and tions to health care are now presenting predictive value (Fischer et al, J Infect Dis, Kaposi's sarcoma. Among the relatively with opportunistic infections as initial 2001). Quantitative PCR techniques for less common pulmonary complications, manifestations of HIV disease, and the PCP diagnosis currently are being devel- cases of disease caused by Aspergillus, frequency with which PCP is encoun- oped, and may be commercially avail- Staphylococcus, and lymphoma are in- tered is greater among such individuals. able in the relatively near future. creasing in frequency. Pathogens that Trimethoprim/sulfamethoxazole may cause pulmonary disease in other Current Status of PCP Diagnosis and (TMP-SMX) remains the drug therapy of immunosuppressed populations and Management choice for PCP, with adjunctive cortico- that cause other types of disease in HIV- steroids being used in patients with infected patients, but that remain rare PCP should be considered in any HIV- severe disease. Pentamidine is also an causes of pulmonary disease in the lat- infected individual with pulmonary dis- effective therapy, but is associated with ter, include CMV, MAC, herpes simplex ease. Although suspicion should be adverse effects. Other treatment options, virus, and Rhodococcus. heightened in patients with lower CD4+ including atovaquone and clindamycin- Changes in the spectrum of HIV- cell counts, it should be remembered primaquine, have not provided sufficient related pulmonary disease have been that