Comprehensive, up-to-date information on HIV/AIDS treatment and prevention from the University of California San Francisco

Although declining in incidence because of prophylactic measures, PCP remains one of the most frequently encountered opportunistic pneumonias in patients with advanced HIV disease.(2-4) Although the radiographic findings in patients with PCP vary, the majority of chest radiographs reveal bilateral, fairly symmetric, fine to medium reticular heterogeneous opacities.(5,6) As the disease worsens, the opacities coalesce and eventually appear as a bilateral homogeneous consolidation. Uncommonly, a more coarse reticular pattern or a miliary pattern may be noted.(7)

Unilateral or unilobar involvement may occur, but the radiographic pattern remains as fine reticular opacities. Predominant upper lobe involvement occurs with increased frequency in patients who have used aerosolized pentamidine for prophylaxis.(8,9) As the use of this form of prophylaxis has waned, the incidence of this appearance has decreased similarly. The presence of hilar or mediastinal adenopathy as well as pleural fluid is rare and should suggest another disease process. These findings usually are seen in patients who have been taking aerosolized pentamidine and have developed disseminated pneumocystosis.(10,11) Some cases of pneumocystosis following use of dapsone prophylaxis have been reported.(12) Calcified hilar and mediastinal lymph nodes rarely occur.(13)

Approximately 10% of patients with HIV disease and subsequently proven PCP have had normal chest radiographs. In some circumstances, gallium scanning or HRCT may demonstrate lung abnormalities, particularly ground-glass opacities on HRCT in these patients.(14) In many institutions, however, treatment is recommended empirically, without a request for further imaging.(15,16)

After appropriate therapy for PCP, radiographic studies reveal evidence of improvement within 10 days and subsequent complete resolution in most patients. However, radiographic improvement may lag behind clinical improvement by several days.(17) Also, abnormalities may be evident for a prolonged period, probably representing interstitial fibrosis.(18) Air-filled cystic spaces or pneumatoceles with thin walls are seen in 10% of HIV-infected patients with PCP,(19) and spontaneous pneumothorax occurs in 5%.(20,21) Resolution of the pneumatoceles may take several months. Focal nodules with or without cavitation represent another rare feature of PCP. Cavity walls usually are thicker and more irregular than pneumatocele walls.(22,23) Approximately 4 days after beginning intravenous trimethoprim-sulfamethoxazole therapy, patients may have chest radiographic findings that imply that their clinical condition has worsened. These findings may be attributable to pulmonary edema, which usually will resolve in 1-2 days with diuretic therapy and/or careful fluid management.

HIV-infected patients may become infected with fungi endemic to some parts of the world.(41,42) Chest radiographs of patients with histoplasmosis predominantly show bilateral, diffuse, coarse, nodular opacities. Other reported findings in patients with HIV disease and clinically proven histoplasmosis include alveolar consolidation, hilar adenopathy, cavitation, pleural fluid, and normal radiographic findings.(43-46)

Patients with advanced HIV disease who have lived in the southwestern United States, northwestern Mexico, or regions of Central and South America may develop systemic coccidioidomycosis, although the advent of effective ART may have led to a decline in incidence.(47) Chest radiographic findings in these patients include diffuse, coarse, nodular opacities that are indistinguishable from those associated with histoplasmosis and are similar to findings in some instances of tuberculosis in patients with advanced HIV disease. Other reported findings include cavitation and, in at least 1 case, CT evidence of hilar adenopathy.(48-51) In a large series of HIV-infected patients with coccidioidomycosis, 65% had diffuse reticulonodular disease, 14% had focal findings, and 16% had normal chest films.(52)

In HIV-infected patients, the findings of cryptococcal pulmonary infection may differ from those seen in nonimmunosuppressed individuals. Some studies have found more disseminated heterogeneous disease, but one report states that there is a higher likelihood of focal homogeneous opacities as well as a greater tendency toward lung nodules and masses.(53) Chest radiographic findings in patients with this infection most commonly include hilar and mediastinal adenopathy, and diffuse, often nodular, heterogeneous opacities. Larger, well-defined nodules and cavitary lesions also are common. In some patients, pleural effusion and miliary disease have been described.(54-57)

Numerous cases of invasive aspergillosis have been observed. Chest radiographic findings in these patients may include focal pneumonia, upper lobe cavitary disease, and bilateral reticular opacities.(58-60) Nodules, pleural effusion, and adenopathy also are reported, but occur less frequently.(61)

In most patients, cytomegalovirus (CMV) infection coexists with other opportunistic infections, particularly PCP. Controversy exists as to whether and to what extent CMV actually contributes to lung pathology.(62) One report states that positive immunostaining for CMV on bronchoalveolar lavage fluid may indicate a need for antiviral treatment.(63) Reliable diagnosis depends on demonstration of CMV inclusions on lung biopsy specimens.(64) In some patients with pathologically proven CMV pneumonia, chest radiographs show bilateral, reticular, interstitial disease. CT scans may reveal bilateral or focal heterogeneous opacities, ground-glass or consolidative changes, and, in many individuals, well-defined solitary or multiple nodules measuring up to 3 cm in diameter.(65) Differentiation of this infection from PCP on the basis of radiographic findings may not be possible.

Conventional bacterial pneumonias occur with increased frequency in patients with advanced HIV disease, although the incidence has declined with the appropriate use of ART.(66) Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus are among the organisms responsible for these pneumonias. Chest radiographic examination in these patients usually reveals unilobar or multilobar air space consolidation (ie, the typical abnormality caused by these pathogens in non-HIV-infected persons). Other findings include parapneumonic effusions.(67) Clinical improvement usually is reflected radiographically within days following appropriate antibiotic treatment.

Nosocomial bacterial infections typically are caused by Pseudomonas aeruginosa, S aureus, and S pneumoniae and usually present with focal unilateral homogeneous opacities, but also may be diffuse and heterogeneous, or diffuse and homogeneous. Pleural effusions were seen in 10% of patients in one series.(68)

Bronchitis, often caused by the same organisms that cause pneumonia, occurs with increased frequency in patients with advanced HIV disease.(69) Manifestations include peribronchial thickening and tram tracking.(70) These findings are not typical of PCP, and may help to distinguish pyogenic infections from PCP. Bronchiectasis also is observed and is better appreciated with CT scanning.(71)

Nocardia infections have been reported in patients with HIV disease.(72) In one HIV-infected patient at San Francisco General Hospital, pulmonary Nocardia caused a homogeneous consolidation in the right middle lobe. Cavitation within areas of homogeneous consolidation also has been noted.(73) In a large series, chest radiographs revealed airspace opacities in 74% of patients and cavitation in 32%.(74)

Rhodococcus equi, a gram-positive bacillus, may cause large, fairly thick-walled cavities and empyema.(75) Lymphadenopathy also is reported.(76,77) CT and HRCT findings include homogeneous opacities with cavitation, ground-glass opacities, centrilobular nodules, and tree-in-bud opacities.(78)

Pulmonary toxoplasmosis is reported in patients with advanced HIV disease.(79-81) Radiography reveals poorly defined nodules scattered throughout the lungs of some patients,(82) and pleural fluid may be present.

The typical radiographic pattern observed in HIV-infected patients with Kaposi sarcoma (KS) consists of poorly defined nodular opacities approximately 1-2 cm in diameter scattered throughout both lungs. Coalescence of opacities to form homogeneous areas of consolidation is seen later in the course of disease. Also seen are diffuse, coarse, linear opacities, particularly in the perihilar and lower lung regions. Hilar adenopathy is demonstrated infrequently in patients with KS, but pleural fluid is observed in 35-50% of patients.

Development of KS generally is slow but, if hemorrhage occurs, the radiographic picture worsens rapidly.(83-85) The chest radiographic findings mentioned previously are virtually pathognomonic for KS, as is the appearance of intrabronchial lesions visualized by bronchoscopy, but nuclear radiology and CT scanning are used occasionally in diagnosis.(86,87) Usually, patients with KS exhibit KS-related radiographic changes late in the course of the disease, although pulmonary KS manifestations occurred before lymphocutaneous manifestations in a few reported cases.(88) Immune reconstitution inflammatory syndrome may lead to flaring of pulmonary KS.(89)

In one series, intrathoracic involvement occurred in 10% of AIDS patients with non-Hodgkin lymphoma (NHL).(90) Abnormalities include pleural effusions, hilar and/or mediastinal lymphadenopathy, perihilar reticulonodular opacities, and well-defined, rapidly growing nodules measuring 0.5-5.0 cm in diameter (Figure 1 and Figure 2).(91-93) At least 1 of these large nodules cavitated after therapy. There is a report of a case of primary pulmonary lymphoma presenting with atelectasis of a lung.(94) The radiographic appearance of multicentric Castleman disease in patients with HIV infection reveals reticular and/or nodular heterogeneous lung opacities, mediastinal lymph node enlargement, and, less commonly, pleural effusion.(95)

Although lung cancer has been described in patients with AIDS, it is controversial whether a cause-and-effect relationship exists.(96,97-99) One series included 22 young HIV-seropositive patients with lung cancer.(100) It is unclear whether these neoplasms are coincidental with HIV disease, or if they might be related to abnormal immune function. In another series, no difference in incidence of lung cancer in young patients was seen in pre- and post-AIDS era populations.(101) In another review, the authors concluded that, although AIDS patients present with lung cancer at an earlier age, a definite cause-and-effect link cannot be established.(102) A recent publication suggests that a higher risk of lung cancer in these patients may be due to a higher smoking prevalence.(103) Radiographic findings include mediastinal adenopathy, hilar and parenchymal masses, atelectasis, and pleural effusions.(104)

Lymphocytic interstitial pneumonitis (LIP) is an index diagnosis of AIDS in the pediatric population. Chest radiographs reveal fine reticular or reticulonodular opacities in about one third of patients, coarse reticular opacities in about 12%, and combined heterogeneous and scattered homogeneous opacities in just over half.(105) The radiographic abnormalities remain stable throughout the course of HIV infection in 75% of patients. With time, lymphadenopathy may develop.(106) The chest radiographic appearance of LIP may be indistinguishable from that of PCP. CT demonstrates small nodules in a peribronchovascular distribution and ground-glass opacities.(107) HRCT may reveal perilymphatic and subpleural nodules when the chest film is normal.(108) Treatment with antiretroviral agents has produced a mixed response but certainly may lead to improvement in clinical and radiographic findings.(109,110)

Patients with HIV-related lymphadenopathy syndrome usually show subdiaphragmatic lymphadenopathy and splenomegaly. No significant hilar or mediastinal adenopathy on chest radiographs or CT scans has been reported in patients with this syndrome alone. The presence of hilar or mediastinal adenopathy in a patient with HIV disease and the lymphadenopathy syndrome suggests the possibility of lymphoma, KS, tuberculosis, or fungal disease. Occasionally, chest radiography in these patients reveals an enlarged spleen. Abdominal or retroperitoneal lymph nodes with central necrosis on CT also are unlikely to be due to HIV lymphadenopathy syndrome. In some cases, needle aspiration or excisional biopsy may be necessary to rule out lymphoma, KS, mycobacterial disease, or other infection.

When treated with effective ART, patients with previously quiescent opportunistic infections may demonstrate new or recurrent clinical and radiologic findings of disease.(111,112,113) This phenomenon has been reported with atypical mycobacteria, fungi, and viruses. Worsening of tuberculosis also may be noted.(114) Some cases of sarcoidosis beginning after initiation of ART have been recognized as well.(115) One case of cyst and nodule formation not associated with definite recurrent infection is reported in a patient with previous TB.(116)

In a review of 351 patients with HIV infection and presumed PCP, 67 patients were ultimately found not to have PCP. Sixteen of these patients had nonspecific interstitial pneumonia (NSIP). The diagnoses were not distinguishable based on clinical characteristics, although those with NSIP had higher CD4 counts. Interstitial opacities were the most common chest film finding in NSIP. In 6 patients these were diffuse, and in 8 they occupied fewer than 2 quadrants. One patient had diffuse alveolar opacities, and another had a normal film.(117)

Candida albicans is the opportunistic organism that most frequently affects the GI tract in patients with HIV disease. The radiographic findings of Candida (monilial) esophagitis range from mild mucosal irregularity of the proximal to mid esophagus, to diffuse nodularity, a cobblestone appearance, extensive plaque formation, and occasional deep ulceration. Rare cases involve large fungus balls and bezoars. Invasive candidiasis can mimic primary or secondary tumor of the esophagus, causing luminal narrowing and masslike thickening of the esophageal wall.(118) Dissemination is unusual, but can lead to abscesses of the liver, spleen, or kidney.(123)

CMV and other herpesviruses can cause esophagitis that is radiographically indistinguishable from Candida infection on contrast-enhanced studies. More characteristic, however, are shallow ulcerations with a surrounding halo of edema or deep, longitudinally oriented ulcers. Nodular or vertical linear plaques are another manifestation. In some cases, the radiographic features of CMV gastritis (shallow ulcers and enlarged folds) are similar to those seen in other forms of gastritis (Figure 3).(124,125)

More commonly, CMV affects the small bowel and colon, causing disease that clinically, radiographically, and pathologically can simulate idiopathic inflammatory bowel disease or ischemic colitis.(126) Contrast-enhanced studies in patients with mild to moderate CMV colitis may reveal superficial erosions, granular mucosa, spasm, and prominent submucosal nodular indentations (2-4 mm), representing lymphoid nodular hyperplasia. In individuals with severe disease, studies may reveal frank ulceration, submucosal hemorrhage ("thumbprinting"), and perforation. The findings may be diffuse or focal; cecal involvement predominates in some series. CT scans typically reveal circumferential colonic wall thickening with submucosal edema and hypoattenuation. Usually the cecum and ascending colon are involved but other areas can be abnormal. Lymphadenopathy usually is not seen.(119)

In patients with HIV disease and cryptosporidiosis, the radiographic manifestations on contrast-enhanced studies are nonspecific and varied, and range from diffuse, regular thickening of duodenal and jejunal folds to a more disorganized, irregular fold pattern. Increased secretions radiographically recognized as dilution and flocculation of the intraluminal barium often are evident in the small bowel and, less commonly, in the colon. CT scans may reveal similar findings of small intestine dilatation, wall thickening, and increased secretion.(127) Antral narrowing has been described when the stomach is involved.(128) Benign pneumatosis also has been reported.(129) Some investigators report a pattern of diffuse colitis when parasitic infestation has persisted for several months.(118,130)

Patients with HIV disease have an increased incidence of infections with atypical mycobacteria, particularly MAC. Patients with disseminated MAC infection associated with HIV disease often complain of systemic and abdominal symptoms, particularly night sweats, abdominal pain, diarrhea, and weight loss. Clinicians often obtain barium studies of the GI tract and abdominal CT in this setting. The most common CT findings are enlarged retroperitoneal and mesenteric lymph nodes (42%), hepatomegaly (50%), splenomegaly (46%), and small bowel wall thickening (14%).(131)

Barium studies of the upper GI tract may reveal esophageal ulceration or small bowel pathologic changes marked by thickened, distorted folds and increased secretions.(132) Abdominal CT frequently (>80%) demonstrates large, bulky, retroperitoneal and mesenteric adenopathy.(133) The lymph nodes usually are clustered and uniform in attenuation value, in contrast to nodes in tuberculosis, which more frequently have low central attenuation and usually are larger.(134) Hepatomegaly may be present and severe,(127) and is more likely in MAC than in M tuberculosis disease.(134) In most cases, specimens obtained by CT-guided biopsy definitively show large, foamy macrophages filled with acid-fast bacteria. The intracellular, rodlike organisms also may stain positive with periodic acid-Schiff (PAS) stain. This latter feature, the clinical presentation, and radiographic and CT findings are similar to findings in Whipple disease, leading to the designation of abdominal MAC infection as "pseudo-Whipple disease," and suggesting that the gut may be one portal of entry in disseminated MAC.(135)

Esophagitis secondary to spread of M tuberculosis from mediastinal nodes may lead to barium radiographic and CT findings of extrinsic masses, ulceration, sinus tracts, and fistulous tracts. Tuberculous colitis occurs chiefly near the ileocecal region, and contrast-enhanced CT scans may reveal thickened bowel wall. Necrotic lymph nodes with low attenuation centers may be seen in association with tuberculosis.(127,134) A recent review states that lymph nodes with central low attenuation are more common, and that lymph nodes are larger (mean 4.0 cm vs 2.0 cm, respectively) with tuberculous involvement than with MAC.(134)

This response to infection with Bartonella henselae and Bartonella quintana results in cutaneous and systemic hemangioproliferation, particularly in patients with very reduced CD4 counts. In lymph nodes, this results in hyperattenuation. In the liver, the disease is called peliosis hepatis and may appear as multiple blood-filled cysts. The spleen also may be involved with these low-attenuation lesions. If the cysts are larger than 2 cm, the differential includes bacillary angiomatosis and lymphoma. The combination of hyperattenuating lymph nodes, larger low-attenuation lesions in the liver and spleen, and severe decrease in CD4 counts suggests bacillary angiomatosis.(119)

Where effective ART is available, the incidence of KS and the outlook for affected patients has improved.(136) Early lymph node and visceral involvement are frequent in HIV-associated KS, especially in patients with advanced immunosuppression. Late in the course of HIV disease, lesions may involve virtually any organ system. Endoscopy reveals that nearly 50% of patients with mucocutaneous KS also have GI KS, although barium radiography reveals only a minority of these lesions.(137) KS can affect any part of the GI tract from the pharynx to the anus. Most persons with GI lesions are asymptomatic, although more advanced KS may involve GI bleeding, obstruction, perforation, and diarrhea. A case of intussusception from an ileal KS lesion has been reported.(138) The typical radiographic manifestations of GI KS are submucosal plaques, some with central ulceration ("target" or "bull's-eye" lesions). Larger polypoid masses are relatively common; circumferential and diffusely spreading lesions are rare.

Initial reports of CT findings in HIV-related KS emphasized the similarities with lymphadenopathy syndrome.(139) Splenomegaly and mild retroperitoneal and mesenteric nodal enlargement are common to both, and do not necessarily indicate widespread involvement with KS, particularly when the nodes are <1.5 cm in greatest diameter.

Bulky nodal enlargement, however, may be the only CT evidence of abdominal KS. KS-affected nodes may show significant contrast enhancement.(140) Bulky adenopathy in HIV-related KS cannot be distinguished radiographically from lymphoma or infections such as MAC, and further investigation by fine-needle aspiration biopsy may be necessary.(141)

Although the characteristic "target" lesions of KS seen on air contrast studies of the GI tract rarely are evident on CT studies, mural thickening may identify larger focal masses. The CT demonstration of focal small hepatic or splenic lesions of KS is uncommon. These lesions may show enhancement on delayed scans.(142)

As with KS in retroperitoneal nodes, KS in the liver or spleen has a nonspecific CT appearance, and biopsy may be necessary to distinguish it from other neoplastic or infectious causes. Usually, liver and spleen involvement consists of microscopic foci along vessels and is not visible radiographically. However, nonspecific hepatosplenomegaly may be seen in up to 41% of patients with KS.(119) Because KS can involve virtually any organ, it may produce unusual intraabdominal lesions that are readily detectable on CT and may be amenable to CT-guided biopsy. In our experience, fine-needle aspiration biopsy is reliable in diagnosing HIV-related KS. Stains of biopsy specimens show cohesive clusters of bland spindle cells arranged in characteristic slitlike spaces.

In addition to KS, a variety of aggressive B-cell lymphomas are associated with HIV disease. To date, NHL has been the most common lymphoma in patients with advanced HIV disease. Hodgkin disease also can occur, however.

In some patients, the manifestations of lymphoma appear before those of advanced HIV disease. In a report of NHL in 90 homosexual men,(90) unique manifestations included a high prevalence of extranodal involvement in HIV-related lymphoma, which affected the brain and bone marrow, as well as abdominal, visceral, and mucocutaneous sites (Figure 4). Of the 90 patients, 88 had extranodal sites of involvement. In addition, patients with HIV-related lymphoma typically had highly malignant histologic subtypes and advanced stages of NHL.

A significant percentage of patients with HIV-related lymphoma demonstrate focal hepatic and splenic lesions (Figure 5). The liver and spleen usually are normal in size but may become enlarged if focal lesions are present.(143) In a series of 19 HIV-related lymphomas, 26% of patients with NHL had biopsy-proven focal hepatic lesions compared with 4-6% of patients without HIV disease.(144) In patients with relatively diffuse hepatic involvement of lymphoma, smaller microscopic foci (<1 cm) occasionally are difficult to recognize on contrast-enhanced CT images. Sonography can be useful in depicting disorganized hepatic echogenicity with small hypoechoic foci in patients with hepatomegaly and no obvious focal lesions on CT scans. Bulky retroperitoneal and mesenteric adenopathy is common. The nodes usually are of soft tissue opacity and do not tend to enhance with intravenous contrast as they do if the cause is KS.(140) In cases of enteric involvement, barium studies may reveal irregularly thickened gastric or intestinal folds.(127)

HIV-related Hodgkin disease appears to be substantially less common than HIV-related NHL. Features of Hodgkin disease, however, are distinctive in the population with HIV disease. Patients with HIV disease and Hodgkin disease typically present with stage III or IV Hodgkin disease, with mixed cellularity or nodular sclerosing histology. In addition, unusual manifestations of Hodgkin disease include involvement of the skin overlying the involved lymph nodes, and bone marrow involvement without splenic lesions. In a series of 10 patients with HIV-related Hodgkin disease studied at San Francisco General Hospital, 2 patients had bulky mesenteric nodal masses, an uncommon feature of Hodgkin disease in the non-HIV-infected population. In addition, CT scanning revealed noncontiguous sites of nodal involvement in which pelvic adenopathy occurred without periaortic involvement.

CT-guided percutaneous needle biopsy of enlarged lymph nodes can be very useful in diagnosing lymphoma. Although the technique requires considerable cytologic skill, the fine-needle biopsy has allowed diagnosis and subtyping of most HIV-related lymphomas in patients treated at San Francisco General Hospital.

The most frequent appearance of untreated Toxoplasma gondii encephalitis on CT scans consists of multiple deep and superficial lesions in both cerebral hemispheres, associated with edema and mass effect. The lesions characteristically are at the corticomedullary junction and in the basal ganglia.(146) The lesions typically are ring enhancing on contrast-enhanced CT or MRI.

The CT appearance of Toxoplasma encephalitis is not pathognomonic; for example, toxoplasmosis may be radiographically indistinguishable from primary CNS lymphoma. In many cases, CT imaging repeated after anti-Toxoplasma medication has been administered may assist diagnosis. If the lesion is due to Toxoplasma, serial CT scans show progressive diminution of contrast-enhanced lesions, edema, and mass within 2-4 weeks of treatment. Clinical improvement usually occurs within 1 week of initiating treatment. With continuous and long-term medical therapy, healing does occur, as evidenced by the return to normal of some scans and, on others, the appearance of areas of encephalomalacia. Because of persistent cellular immune defects in patients with HIV disease, however, this healing process may reverse when medical therapy is interrupted. CT scanning is a reliable indicator of recurrent lesions, which look the same as the original lesions. In one report, single photon emission computed tomography (SPECT)-thallium nuclear scanning was shown to differentiate toxoplasmosis (negative examination) from lymphoma (positive examination).(147) In some institutions, sequential thallium gallium scanning has been used to distinguish between toxoplasmosis and lymphoma.(148) If clinical status and CT scans fail to show a satisfactory response to medical therapy, biopsy of CNS lesions may be warranted.

MRI appears more sensitive than CT scanning in the detection of HIV-related CNS pathology.(149) If CT images fail to reveal a lesion accessible to biopsy sampling, then MRI is a useful adjunct. Some researchers believe that MRI is the method of choice for all HIV-related CNS pathology, and obviates CT scanning in most cases.

Many instances of encephalitis and encephalopathy are direct or immunologically mediated results of HIV infection. Clinical manifestations of the AIDS dementia complex, including personality changes, confusion, memory loss, and motor deficits, develop over weeks to months. The most common CT finding in patients with HIV encephalitis is diffuse atrophy and sulcal dilatation.(150) CT scanning also may detect low-attenuation lesions in the white matter, although MRI is more sensitive in this regard.(150,151) MRI demonstrates increased signal on T2-weighted images in the periventricular white matter and centrum semiovale in patients with HIV encephalitis, and a diffuse increase in white matter signal intensity on long time of repetition (TR) images with HIV leukoencephalopathy.(152) No mass effect or enhancement of these lesions is demonstrated. Progressive atrophy is manifest on follow-up studies and reflects clinical deterioration. This correlation is not perfect, however, and some patients with clinical disease may have normal studies. Some investigators suggest that ART including zidovudine results in both clinical improvement and evidence of such improvement on MRI.(151,153) Although effective antiretroviral therapy reduces the frequency of many HIV-associated diseases, at least 1 autopsy study failed to find a decrease in HIV encephalopathy after effective ART became available.(154) MRI studies in a small number of patients receiving ART have shown that initial worsening on imaging may be followed by ultimate clinical improvement, and that the signal abnormalities may stabilize or even regress on subsequent examinations.(155) However, in another series of patients who experienced viral rebound on ART, a severe encephalopathy, perhaps related to the individuals' restored immune status, has been reported.(156)

Cryptococcus neoformans is a common cause of opportunistic CNS infections in patients with AIDS. CT scanning may demonstrate nonspecific findings such as atrophy or hydrocephalus. MRI may demonstrate focal parenchymal cryptococcomas, cysts, miliary parenchymal disease, or dilated Virchow-Robin spaces.(157)

CNS tuberculosis may take several forms. Tuberculous meningitis occurs with greater incidence in areas where endemic tuberculous infections are frequent. CNS infection occurs without evidence of tuberculosis elsewhere in the body. Contrast-enhanced CT scanning demonstrates meningeal enhancement in the vicinity of the basal cisterns and over the cerebral cortex. Communicating hydrocephalus is relatively common and changes may be followed with CT scanning. Infarcts, most commonly in the distribution of the middle cerebral artery, also occur. Tuberculomas generally are seen in the supratentorial region, particularly frontal and parietal lobes in adults, and in the infratentorial region in children. Tuberculomas may be solitary or multiple, and contrast-enhanced CT scans may show ring enhancement with irregular walls. Edema often surrounds the lesions. Tuberculous abscesses are uncommon, may be solitary or multiple, and often are indistinguishable from pyogenic abscesses. Contrast enhancement of the walls is typical.(158)

MRI perhaps is more sensitive than CT for detecting tuberculous infection of the CNS. In tuberculous meningitis, gadolinium-enhanced T1-weighted images demonstrate meningeal enhancement in the basal cisterns, throughout the sulci, and over the convexity of brain. Other findings more likely to be detected by MRI than by CT include communicating hydrocephalus, tuberculomas, and infarct.

On MRI, tuberculomas demonstrate hypointensity relative to brain tissue on T1-weighted images and are hyperintense on T2-weighted images when the tuberculoma has a caseating liquid center. Tuberculomas with solid centers may reveal hypointense or isointense T1- and T2-weighted images. Gadolinium-enhanced T1-weighted images reveal rim enhancement, and lesions may be indistinguishable from pyogenic abscesses. Resolution of lesions can be verified with CT or MRI following antituberculous therapy.(159)

This CNS infection is caused by JC virus, an opportunistic human polyomavirus. Infection is characterized by several foci of white matter demyelination. Reactivation of virus in immunodeficient hosts may cause progressive multifocal leukoencephalopathy (PML). Clinically, patients present with altered mental status, personality changes, memory loss, or sensory abnormalities. Characteristically, CT scanning demonstrates 1 or more low-attenuation white matter lesions. Mass effect and contrast enhancement are not usual, but may occur.(160,161) MRI is more sensitive than CT in establishing the diagnosis. T2-weighted images demonstrate increased signal intensity in the periventricular and subcortical white matter. The parietooccipital and frontal lobes are more commonly involved. Bilateral involvement is common. MRI usually reveals isointense or hypointense T1-weighted images and increased signal intensity on T2-weighted images. Findings may be indistinguishable from those associated with HIV encephalitis, although the latter process is more often diffuse and periventricular, whereas PML is more commonly subcortical and focal,(151) and lesions of HIV encephalitis tend to be isointense on T1 images, whereas PML generally is hypointense. More recent work suggests that magnetic resonance spectroscopy and magnetization transfer imaging, a different type of MRI, may be better modalities for diagnosing and following this disease.(162) Effective ART has led to some improvement in morbidity and survival, but also has led in some instances to worsening secondary to presumed immune reconstitution inflammatory syndrome.(163)