Search

Eye disease is a well-documented complication of HIV infection. Opportunistic infections generally comprised the majority of pre-antiretroviral therapy (ART) eye complications. With the introduction of ART, opportunistic infections diminished. However, early ART regimens were cumbersome regarding side effects and pill burden, making patient compliance difficult. Newer ART regimens are better tolerated and consist of fewer pills, theoretically making compliance easier and therapy more effective. The aim of this chart review study is to examine eye disease epidemiology in HIV patients as ART has evolved. We reviewed 222 admissions at Thomas Jefferson University Hospitals for 188 patients. These cases were divided into two groups. The first group was comprised of patients admitted from 1995 through 2003, while the second group consisted of patients admitted from 2003 to 2010. Eye disease epidemiology was compared between the two groups. Our study did note a significant decrease in eye diseases caused by opportunistic infections in the 2003-2010 patient group. Noninfectious eye disease is a significant complication in this group.

We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 μL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.

Esophageal ulcer (EU) represents an important comorbidity in AIDS. We evaluated the prevalence of EU, the accuracy of the endoscopic and histologic methods used to investigate viral EU in HIV-positive Brazilian patients and the numerical relevance of tissue sampling. A total of 399 HIV-positive patients underwent upper gastrointestinal (UGI) endoscopy. HIV-positive patients with EU determined by UGI endoscopy followed by biopsies were analyzed by the hematoxylin-eosin (HE) and immunohistochemical (IH) methods. EU was detected in 41 patients (mean age, 39.2 years; 23 males), with a prevalence of 10.27%. The median CD4 count was 49 cells/mm(3) (range, 1-361 cells/mm(3)) and the viral load was 58,869 copies per milliliter (range, 50-77,3290 copies per milliliter). UGI endoscopy detected 29 of 41 EU suggestive of cytomegalovirus (CMV) infection and 7 of 41 indicating herpes simplex virus (HSV) infection. HE histology confirmed 4 of 29 ulcers induced by CMV, 2 of 7 induced by HSV, and 1 of 7 induced by HSV plus CMV. IH for CMV and HSV confirmed the HE findings and detected one additional CMV-induced case. UGI endoscopy showed 100% sensitivity and 15% specificity for the diagnosis of EU due to CMV or HSV compared to HE and IH. HE proved to be an adequate method for etiologic evaluation, with 87% sensitivity and 100% specificity compared to IH. The number of samples did not influence the etiologic evaluation. The data support the importance of IH as a complementary method for HE in the diagnosis of EU of viral etiology.

Rhodococcus equi is a gram-positive, coryneform bacterium that causes zoonotic infection mainly in horses and foals. It sometimes affects humans presenting as cavitary pneumonia. Immunocompromised patients, including HIV-infected patients, are more susceptible to R. equi infection. We present 10 cases of R. equi infection in HIV-positive patients admitted to our institute from 1991 to June 2008. Moreover, we have reviewed 272 cases of R. equi infection in HIV-infected persons, published from 1986 through 2008. With respect to the literature data, the R. equi strains isolated in our case series showed lower sensitivity to ceftriaxone, amoxicillin/clavulanic acid, and cotrimoxazole. Prompt diagnosis, early initiation of antiretroviral treatment and combined antimicrobial treatment seem to be effective to eradicate the infection and to improve the outcome.

Although Legionnaires' disease occurs more commonly in patients with some degree of immunosuppression (diabetes, chronic lung disease, end stage renal disease, cancer, etc.), it has been infrequently described in patients infected with human immunodeficiency virus (HIV) and AIDS. Some studies suggest that pneumonia caused by Legionella tends to present with more severe clinical features and complications in the HIV-infected population. The use of antibiotic prophylaxis or the association of severe pneumonia with other pathogens may account for under diagnosis of the disease. We diagnosed five cases of Legionella pneumonia in patients with HIV infection at our institution during a 1-year period. The cases seen ranged in severity, regardless of the CD4(+) counts of the patients. Based on our observations, it seems impossible to discern whether HIV infection is an additional risk factor for Legionnaires' disease. We describe those five cases and review the available literature.

A prospective study of 55 confirmed or presumptive cases of cerebral toxoplasmosis in HIV positive patients in Brazil was performed to describe clinical characteristics and to identify predictive factors for clinical response to the anti-Toxoplasma treatment. Cerebral toxoplasmosis led to the diagnosis of HIV infection in 19 (35%) patients, whereas it was the AIDS defining disease in 41 (75%) patients. Of these, 22 (54%) patients were previously know to be HIV-positive. At diagnosis of cerebral toxoplasmosis, only 4 (7%) patients were on highly active antiretroviral therapy (HAART), and 6 (11%) were receiving primary cerebral toxoplasmosis prophylaxis. The mean CD4+ cell count was 64.2 (+/- 69.1) cells per microliter. Forty-nine patients (78%) showed alterations consistent with toxoplasmosis on brain computed tomography. At 6 weeks of treatment, 23 (42%) patients had complete clinical response, 25 (46%) partial response, and 7 (13%) died. Alteration of consciousness, Karnofsky score less than 70, psychomotor slowing, hemoglobin less than 12 mg/dL, mental confusion, Glasgow Coma Scale less than 12 were the main predictors of partial clinical response. All patients were placed on HAART within the first 4 weeks of diagnosis of cerebral toxoplasmosis. One year after the diagnosis, all available patients were on HAART and toxoplasmosis prophylaxis, and only 2 patients had relapse of cerebral toxoplasmosis. In Brazilian patients with AIDS, cerebral toxoplasmosis mainly occurs as an AIDS-defining disease, and causes significant morbidity and mortality. Signs of neurologic deterioration predict an unfavorable response to the treatment. Early start of HAART seems to be related to better survival and less relapses.

There is increasing concern that patients with chronic HIV infection may be at increased risk of nonalcoholic fatty liver disease (NAFLD), which can evolve into nonalcoholic steatohepatitis (NASH) and cirrhosis. Multiple factors have been hypothesized to be necessary for the development and progression of this condition. Potential risk factors, which tend to accumulate in the HIV-positive population, include metabolic derangements, chronic inflammation, hepatitis coinfection, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTIs). HIV-associated conditions such as hyperlactatemia and lipodystrophy frequently overlap with fatty liver disease. The cornerstone of management of HIV-associated fatty liver disease is currently to treat the predominant underlying condition. There is a need for more epidemiologic data to better define the role of comorbidities and drugs in the development of NAFLD. Further work is also needed to elucidate the pathogenesis and to evaluate the therapeutic effect of treating comorbidities and avoiding certain antiretroviral drugs.

Immune reconstitution disease caused by Mycobacterium avium complex (MAC) infection presenting shortly after the introduction of highly active antiretroviral therapy (HAART) has been reported with increasing frequency in persons with HIV-1 infection during the past several years. Several therapeutic modalities have been utilized for this entity, but the optimal means of treating MAC immune reconstitution disease remains unclear. We now describe a patient who underwent some of these therapies. We then review the therapeutic outcomes from the numerous case reports of this disorder. Finally, we propose recommendations and a clinical algorithm regarding the optimal means of treatment of MAC immune reconstitution disease during HIV-1 infection.

Although infection with Mycobacterium avium complex (MAC) is common in HIV-infected patients with CD4+ T cell counts less than 100/mm3, localized infection of the breast is uncommon. A brief literature review of mastitis from atypical mycobacteria is presented, along with the first reported case of localized MAC infection of the nonaugmented breast in an HIV-infected woman taking highly active antiretroviral therapy.

Kaposi's sarcoma (KS) and bacillary angiomatosis (BA) may be histologically similar. A precise diagnosis is required because of the different management of these diseases. KS or BA involving bone marrow is rare in patients with and without acquired immune deficiency syndrome (AIDS). We report the case of a 40-year-old human immunodeficiency virus (HIV)-positive homosexual male who presented with small KS lesions in the skin and BA in the bone marrow that histologically were similar. Laboratory evaluation revealed anemia and thrombocytopenia; CD4 count was 103/mm3, and the viral load was 750,000 HIV-1 mRNA copies per milliliter in plasma. Bartonella henselae, the etiologic agent of BA, was isolated from a blood culture. DNA sequences of human herpesvirus-8 (HHV-8), the putative etiologic agent of KS, were identified by polymerase chain reaction (PCR) in skin and bone marrow specimens, but antibody anti-HHV-8-encoded protein ORF73, localized signals only in the skin-KS lesion. The patient received clarithromycin and cefotetan for the BA, and antiretroviral therapy for the HIV infection. The skin lesions gradually regressed, the HIV-1 mRNA copy number decreased to less than 400 per milliliter and the CD4 lymphocyte count increased to 665/mm3. In conclusion, vascular lesions of BA and KS may be clinically and histologically similar, both may be associated with advanced AIDS, and an accurate diagnosis is required because of their different management.

This report describes the case of a 4-year-old human immunodeficiency virus (HIV)-infected girl with Salmonella typhimurium bacteremia and pneumonia. The girl presented with a history of fever for 1 month and mild pulmonary symptoms. Subsequent studies revealed previously undiagnosed HIV disease.

The purpose of this study was to describe the clinical profile of end-stage acquired immune deficiency syndrome (AIDS) since the advent of highly active antiretroviral therapy (HAART). A cross-sectional examination of human immunodeficiency virus (HIV)-infected patients who attended a public HIV outpatient clinic and died between 1996 and 2001 was conducted (n = 669). All clinical and demographic data were collected from the Centers for Disease Control (CDC) Adult Spectrum of Disease database. The prevalence of first-time acquisition of AIDS-defining conditions 12 months before death were evaluated. The prevalence of renal disease, hepatic disease and substance use were also evaluated. The majority of the patients were 35 years old or older, male, African American and HAART-experienced. The six AIDS-defining conditions with the highest percentages of first-time acquisition in the last 12 months of life were HIV dementia (91.8%), progressive multifocal leukoencephalopathy (PML) (91.7%), wasting (90.9%), Mycobacterium avium complex infection (MAC) (80.0%), lymphoma (78.6%), and cytomegalovirus infection (CMV) (78.1%). Forty-four percent of the patients were diagnosed with at least one of these six conditions 12 months before death. More than one third of the patients had renal or hepatic failure, injecting drug use (IDU) as the HIV risk factor, and history of substance use. AIDS-defining conditions continue to have an impact on mortality, especially the neurologic conditions and wasting. However, other conditions, such as renal and hepatic disease, are becoming important causes of mortality because the HIV-infected population now includes more drug users, and HIV-infected patients are surviving for longer periods. These results should help clinicians better time the discussion of end-stage options and improve the patient's quality of life.

Two children (ages 12 and 13 years) with transfusion-acquired human immunodeficiency virus (HIV) infection presented with facial pain and rhinorrhea. Radiographic imaging showed extensive paranasal sinus disease, presumed to be bacterial sinusitis, and the patients were treated with broad-spectrum oral antibiotics. Both patients were unresponsive to oral agents and were switched to intravenous antibiotics. Despite aggressive antimicrobial therapy, one patient (case 1) developed increased periorbital swelling and proptosis, and the other patient (case 2) developed symptoms of nasopharyngeal obstruction. Repeat imaging showed progression of the infiltrative process extending from the paranasal sinuses into the orbit (case 1), and nasopharynx (case 2). Surgical exploration and tissue biopsies were performed on both patients and the histopathology was consistent with Burkitt's/Burkitt's-like lymphoma. Combination systemic and intrathecal chemotherapy resulted in a complete remission in both patients. These reports illustrate the fact that Burkitt's/Burkitt's-like lymphoma in the paranasal sinuses may initially masquerade as an acute bacterial sinusitis. The ability of the tumor to extend rapidly from the sinuses into the orbit and nasopharynx reinforces the importance of early diagnosis and treatment. Burkitt's/Burkitt's-like lymphoma in the paranasal sinuses has not been previously described in HIV-infected children.

Cytomegalovirus (CMV) can cause life-threatening disease in immunocompromised patients, such as those with human immunodeficiency virus (HIV). It is a rare but important cause of ulceration in the female genital tract. We report on three cases of CMV disease in the female genital tract. One patient presented with vulvar ulceration and fevers, and two patients presented with bleeding cervical lesions. All diagnoses were confirmed by histology. All patients were treated with intravenous ganciclovir with good result. CMV disease of the female genital tract may result in significant morbidity, with fever, pain, bleeding, and superinfection, and it may be associated with the development of pelvic inflammatory disease and cervical intraepithelial neoplasia. There are several options for diagnosis and for safe treatment.

This case report describes Nocardia pericarditis in a newly diagnosed human immunodeficiency virus (HIV) patient as an initial manifestation. Previously, two cases of Nocardia pericarditis were reported in patients with established HIV infection. To our knowledge this is the first case of Nocardia pericarditis as an initial manifestation of HIV infection. This case substantiates and emphasizes the importance of identifying Nocardia as an infectious cause of pericarditis in patients with acquired immunodeficiency. Long-term survival may be achieved with a combined medical and surgical approach.

Chagas' disease can reactivate in patients with AIDS and present as a brain mass lesion or an acute diffuse meningoencephalitis indistinguishable from other opportunistic infections or neoplastic processes, such as toxoplasma encephalitis or central nervous system (CNS) primary lymphoma. The CNS tumor-like lesion is the most common manifestation of Chagas' disease reactivation in AIDS patients. The prognosis of untreated cases is grim and underscore the need for safe and effective therapeutic agents.

A patient with advanced AIDS presented with right conjugate gaze palsy and impaired adduction on left gaze (the one-and-a-half syndrome). The responsible pontine lesion involved the ipsilateral abducens nucleus and the adjacent medial longitudinal fasiculus (MLF), as demonstrated by magnetic resonance imaging (MRI). Tuberculosis (TB) was the etiology of the brainstem lesion. The patient had complete recovery after anti-tuberculosis treatment. The nuclear location of the tuberculoma is unusual and the reversal of this neuro-ophthalmologic syndrome is noteworthy.

To determine the effect of an HIV counseling service on the incidence of HIV and tuberculosis infection and on the fertility rate in a large workforce cohort of adult men and women from Kinshasa, Democratic Republic of Congo (formerly Zaire), we conducted a 2-year prospective longitudinal cohort study, two large Kinshasa businesses (a commercial bank and a textile factory). We determined baseline HIV-1 seroprevalence, HIV-1 and tuberculosis mortality/morbidity, and fertility rates during 24 months of follow-up on 8866 employees and 6411 wives of male employees. The baseline HIV-1 seroprevalence was 2.8% in male employees (n = 6657), 8.4% in female employees (n = 417), and 2.4% in the wives of male employees (n = 4692). The HIV-1 seroincidence per 100 person-years of follow-up in these three groups was 0.9, 0.5 and 0.8, respectively. The incidence of tuberculosis was 2.4/100 person years in persistently seropositive individuals compared with a 0.38 rate in persistently seronegative individuals (p < 0.01). The annual fertility rate in persistently seronegative women was 250.0/1000 women compared with a rate of 140/1000 in persistently seropositive women (p < 0.001). Forty-eight (44%) of 105 male employees and 17 (26%) of 60 wives of male workers who died during follow-up were HIV-1 seropositive. HIV infection was responsible for nearly one half of all deaths in this large workforce. Tuberculosis incidence was six times higher in HIV-1-infected compared with uninfected individuals. Counseling of HIV-infected women and their husbands appeared to be effective as their cumulative fertility rate was 44% lower than the rate in similarly aged uninfected women.

A significant increase in the number of elderly patients first diagnosed with HIV infection at the time of presentation with an AIDS-related opportunistic infection has recently been reported. This suggests a significant delay in the diagnosis of HIV infection. Few data are available describing such cases and their outcome. We restrospectively reviewed records of all elderly patients (> 50 years of age) admitted to a New York City hospital over a 3-year period with confirmed Pneumocystis carinii pneumonia (PCP). The mean age was 57.9 +/- 6.6 years. In 80% (8 of 10 cases), the diagnosis of HIV infection was made at presentation with PCP. The mean CD4 count was 34.2 +/- 39.2/mm3 (1-117/mm3), indicating advanced AIDS. The clinical presentation of PCP was similar to that in younger patients. With prompt and appropriate therapy, a 70% survival rate for this hospitalization was achieved, similar to that reported in younger age groups. The diagnosis of HIV infection was not considered until presentation with PCP at an advanced stage of AIDS in 80% of these elderly patients, thus delaying institution of HIV treatment and counseling. Early consideration of HIV infection in the elderly is of importance because of the rising number of AIDS cases in this age group.

Disseminated histoplasmosis in AIDS patients is the focus of this paper. Cutaneous lesions are reported as a frequent clinical sign. Bone marrow aspiration and biopsy, blood cultures (lysis-centrifugation technique), bronchoalveolar lavage, and skin lesion scrapings are the most effective diagnostic methods. The identification of a specific antigen in blood and urine may be a rapid means of evaluation and follow-up of patients with this disease.

Chancroid is a sexually transmitted disease caused by the bacterium Haemophilus ducreyi. It usually presents as a genital ulcer and may be associated with regional lymphadenopathy and bubo formation. H. ducreyi infection is predominantly seen in tropical resource-poor regions of the world where it is frequently the most common etiological cause of genital ulceration. Genital ulcer disease has been shown to be an extremely important co-factor in HIV transmission. With the advent of the AIDS epidemic, there has been increased research effort to elucidate those factors involved in the pathogenesis of chancroid. Several putative virulence factors have now been identified and isogenic H. ducreyi mutants constructed by mutagenesis of their encoding genes. This approach has facilitated investigations into the role each of these putative virulence factors may play in H. ducreyi pathogenesis through the use of in vitro and in vivo model systems. One major goal of current chancroid research is to identify antigens which are immunogenic and could form the basis of a vaccine against H. ducreyi infection. Such a vaccine, if shown to be effective in decreasing the prevalence of chancroid, could have the added benefit of slowing down the HIV incidence rates in those populations where chancroid is a major co-factor for HIV transmission.

Viral folliculitis is an infrequently reported entity. We describe two patients with viral folliculitides, including a case of herpetic sycosis caused by herpes simplex (HSV) and a case of herpes zoster (HZ) without blisters. Clinicians should consider viral etiologies in the differential diagnosis of superficial infectious folliculitis, especially those cases refractory to antibacterial or antifungal therapy.

Visceral leishmaniasis (kala-azar) is a worldwide disseminated protozoal infection primarily transmitted by sand flies. Because host defense against this intracellular infection is T-cell-dependent, kala-azar has predictably joined the list of AIDS-related opportunistic infections in endemic areas. The vast majority of patients with AIDS-associated kala-azar are currently found in southern Europe (the Mediterranean basin, especially Spain in injection drug users); future cases will inevitably arise in other endemic regions including India, East Africa and Sudan, and Brazil. In CD4 cell-deficient HIV-infected individuals, kala-azar likely represents recrudescence of previously controlled asymptomatic infection; in drug users, newly acquired infection may result from transmission via shared needles. Coinfected patients are frequently parasitemic and may show atypical clinical presentations, unusual multi-organ involvement, and absent antileishmanial antibodies. Diagnosis is made by microscopic examination or culture of aspirate or biopsy of any involved tissue (primarily bone marrow) or by blood smear or culture. Conventional treatment (pentavalent antimonials) induces initial remission in about 50% of patients; amphotericin B and its new lipid formulations appear more active. If suppressive maintenance therapy is not used, relapse within 1 year is typical. In AIDS patients with a first episode of visceral kala-azar, up to 25% die within 1 month if treatment is stopped. Optimal primary and secondary prophylaxis for AIDS-related kala-azar remain to be determined; life-long maintenance therapy is becoming an accepted approach.

Selected periodontopathic bacteria were sought in 20 HIV-infected English patients and eight noninfected control subjects with similar periodontal status, using highly specific DNA probes. Actinobacillus actinomycetemcomitans (A. a), Porphyromonas gingivalis, Campylobacter rectus, Prevotella intermedia, and Fusobacterium nucleatum were more frequently detected and were found at higher levels in HIV-infected individuals than in controls. Significantly increased levels of Treponema denticola but, in contrast, lower levels of Eikenella corrodens were found in nonbleeding sites of HIV-infected patients compared with controls. The results of the present investigation on English patients suggest a periodontopathogenic role for A. a, P. gingivalis and C. rectus, and possibly P. intermedia and are in general accord with most previously reported data from the United States. Longitudinal studies are now required to determine more precisely the association between periodontopathic microflora, immune competence and periodontal health and disease in HIV-infected persons.

To evaluate the natural history and the impact that different strategies have had on HIV infection and its associated conditions, a cohort of 970 patients (432 had AIDS) who had been seen over a period of 13 years were studied. The incidence of new HIV-infected patients had increased steadily since 1985, peaking in 1993 (52.9 cases/100,000 population), to significantly decrease in the subsequent years. The most common AIDS-defining illnesses (ADIs) were tuberculosis (52.3% of the patients), Pneumocystis carinii pneumonia (30%), and candidal esophagitis (28.6%). The frequency of new cases of tuberculosis per patient with ADI clearly decreased over this period (p < 0.0001), whereas that of P. carinii pneumonia decreased slowly until 1994, to fall thereafter to about half the previous levels (p = 0.005). Candidal esophagitis showed a biphasic pattern, the second peak probably due to the emergence of fluconazole resistance. The number of ADIs per patient increased from the beginning of the observation period, peaking in 1995 (1.67 ADI/patient), followed by a statistically significant decrease that, in 1997, reached the 1987 levels (1.22 ADI/patient). We conclude that the clinical spectrum of HIV infection is improving in the last years. Except for tuberculosis, prophylaxis for other ADIs, although effective, does not seem to have had a dramatic impact on occurrence. The most impressive reductions have been observed only after the introduction of antiretroviral combination therapy.

The frequency of Nocardia infection in HIV-infected patients has increased during the past few years from 0.3% in 1985 to 1.8% in 1989. Although it is not of great concern as an AIDS-associated infection, the nonspecific clinical presentation in these patients might be confused with other lung infections such as tuberculosis (TB). The mortality rate can be as high as 60%. The authors diagnosed three homosexual men with nocardiasis among 1060 HIV-infected patients (0.2%) in a tertiary care center in Mexico City from 1981 to 1997. The mean age was 32 years. The CD4 count was less than 260 cells/mm3 in all these individuals. The clinical presentations were subacute sinusitis, chronic localized abdominal abscess, and acute disseminated nocardiasis. The respective associated infections were none; TB and cytomegalovirus (CMV); and candidiasis, TB, CMV, Isospora belli, and disseminated Mycobacterium avium complex (MAC). Trimethoprim/sulfamethoxazole (TMP/SMX) was the treatment in all the cases; at the time of this writing, two patients were living and one had died during the acute episode. A literature search uncovered 130 cases of Nocardia infection in HIV patients since 1982. According to the published data and our results, nocardiasis should be suspected in those HIV-infected patients who (1) do not respond to appropriate antituberculous treatment; (2) are intravenous drug users; and (3) develop a characteristic pericardial infection. Finally, adequate surgical or percutaneous drainage of abscesses are extremely valuable for diagnosis and therapy.

The frequency of skin problems in patients with HIV infection and AIDS is well known from clinical experience and from the reports of cohorts of patients followed over months and years. Decreased mucocutaneous immunity often accounts for the earliest clinical signs seen in HIV-infected patients. As HIV disease progresses, these skin manifestations may become more severe and varied. In advanced immunosuppression, opportunistic pathogens may present as atypical cutaneous lesions. The following two cases illustrate a number of important points in relation to the management of skin disease in HIV patients.

Histoplasmosis is one of the most common opportunistic infections in HIV-infected patients who reside in endemic areas, and "imported infections" also occur elsewhere. A recent decline in the incidence of histoplasmosis appears to correlate with advances in antiretroviral therapy. Histoplasmosis occurs due to either dissemination of newly acquired infection or reactivation of latent foci of infection. Major risk factors include a CD4 count < or = 150/microL, positive complement fixation serology for the Histoplasma capsulatum mycelial antigen, and a history of exposure to chicken coops; in addition, suboptimal antiretroviral therapy seems likely to be a risk factor. Although there are a variety of clinical manifestations, most patients present with a several-week history of fever, chills, weakness, and weight loss. Diagnosis is based on positive cultures of blood, bone marrow, or other sites; detection of antigen in serum or urine; or characteristic histopathologic findings in biopsy specimens. Induction therapy consists of amphotericin B for acutely ill patients or itraconazole for patients with mild to moderately severe disease. Subsequent lifelong maintenance therapy with itraconazole is recommended. In patients with CD4 counts of < or = 150/microL, itraconazole is effective primary prophylaxis.

In the first part of our review, we discussed the general evaluation and clinical presentation of the various hepatic infections occurring in patients with AIDS. In addition, we focused on specific hepatic parenchymal infections. In this article, we will discuss the major clinical syndromes arising from opportunistic infections affecting the gallbladder (acalculous cholecystitis), biliary tree (AIDS-cholangiopathy), and pancreas (pancreatitis). Acalculous cholecystitis can develop in patients with AIDS who have not experienced the severe precipitating physiologic stresses normally required in patients without AIDS. The most common presentation is with right upper quadrant (RUQ) pain and tenderness. The diagnosis is a clinical one since there is no standard test, other than surgery. Cholecystectomy is the treatment of choice. The most common AIDS-associated infective complication of the biliary tree is AIDS-cholangiopathy. This is best viewed as a form of secondary sclerosing cholangitis resulting from a variety of opportunistic infections within the biliary tree. Affected persons present with RUQ pain and have marked elevations in the canalicular enzymes, alkaline phosphatase, and gamma-glutamyl transferase. Morphologic abnormalities are identified by endoscopic retrograde cholangiopancreatography. These include stricturing, dilatation, and beading of the biliary tract. Endoscopic sphincterotomy of the papilla of Vater may provide symptomatic relief for patients with papillary stenosis. Opportunistic infections within the pancreas gland have been documented in both pre- and postmortem studies. However, the true incidence of pancreatitis related to infections is unknown. The presentation is similar to that of pancreatitis from other causes. A computerized tomogram of the abdomen is the investigation of choice. Tissue aspiration or biopsy of the pancreas is required to demonstrate the presence of an opportunistic infection. The management is usually supportive, as it is rare that a specific infection is identified and treated.

Infections of the liver and biliary tract are common during the course of AIDS. A variety of viral, bacterial, fungal, and other opportunistic infections can present with hepatobiliary involvement as either the primary site of infection or secondary to a disseminated process. Coinfection with hepatitis B and C are particularly common due to the shared means of transmission of these viruses with HIV. The typical presenting features of hepatobiliary infections are right upper quadrant (RUQ) pain and abnormal liver function tests. Initial evaluation should include an RUQ ultrasonogram, which will usually identify abnormalities in the biliary tract and may demonstrate some parenchymal abnormalities as well. A liver biopsy is necessary to determine the etiology of focal hepatic lesions or opportunistic infections within hepatic parenchyma when other less invasive tests are negative or inconclusive. Special stains and culture techniques are required to identify specific organisms in the biopsy specimen. HIV-related biliary disorders include acalculous cholecystitis, which is a potentially serious condition requiring prompt recognition and gallbladder decompression. AIDS-cholangiopathy is a form of cholangitis involving the intra- and/or extrahepatic biliary tree. Endoscopic retrograde cholangio-pancreatography (ERCP) is the test of choice, demonstrating the stricturing, dilatation, and beading of bile ducts seen in this condition. Endoscopic sphincterotomy of the papilla of Vater may provide symptomatic relief for patients with papillary stenosis. Opportunistic infections of the pancreas have been reported. Evaluation should include a computerized tomogram of the abdomen and possible pancreatic tissue aspiration or biopsy. Management of pancreatitis is supportive.

Fever of unknown origin constitutes a common problem in HIV-infected patients that, paradoxically, has received little attention in the literature. A review on this topic collecting data from different series showed that mycobacterial infections, particularly tuberculosis, were responsible for the fever in more than half of the patients. However, the relative frequencies of the different etiologies may vary substantially depending on the local prevalences of certain infections. With the notable exception of tuberculosis, which may develop at any stage of HIV infection, fever of unknown origin usually presents in patients with advanced disease when the CD4 cell count is below 100/microliter. In this overview we stress, from a practical point of view, some points to be considered in the evaluation of the HIV-infected patient who presents with fever of unknown origin, as well as the usefulness and yield of several diagnostic procedures.

The world-wide prevalence of hepatitis C virus (HCV) is approximately 1%. Being primarily a blood-borne virus, the major risk factors for HCV include the receipt of blood and blood products, as well as intravenous drug use. As a result, many individuals infected with HIV are also infected with HCV. Any effect of coinfection on progression of either HIV or HCV is likely to have a tremendous impact on the mortality and morbidity of these individuals and should be considered when managing coinfected individuals. This review will describe the epidemiology and clinical manifestations of HCV and will consider the evidence for an impact of coinfection on the progression of both viruses.

The aggressive multidrug regimen of highly active antiretroviral therapy (HAART) has offered some degree of promise of immune reconstitution in AIDS patients, a phenomenon that theoretically would impact positively on the incidence and severity of opportunistic infections. Some studies already have noted complete regression of cytomegalovirus (CMV) retinitis without specific use of anti-CMV agents in patients undergoing HAART. However, the role of HAART in CMV retinitis remains controversial among investigators. This review of the salient details regarding the controversies associated with CMV retinitis and the immune recovery hypothesis is meant to shed light on current and future therapeutic issues concerns. Early data seem to predict a decline in CMV retinitis. However, some investigators have noted that increased CD4 T-lymphocyte counts may not protect against CMV retinitis; therefore, the diagnosis cannot be excluded based on count alone. There is also the question of whether CMV retinitis progression in any way represents failure of HAART in those patients receiving this type of combination therapy. HAART is seen as an encouraging development in the treatment of AIDS and opportunistic infection, but its more specific therapeutic effect on CMV retinitis requires further research with controlled prospective clinical trials.

Strongyloides stercoralis infection in humans continues to be a subject that has frequently inspired reviews and papers. Within the AIDS epidemic, interest gathered momentum with the inclusion of this infection in the indicator diseases list, and its subsequent removal 5 years later by the CDC. These actions have prompted a debate as to whether this infection has special significance in patients with AIDS and whether its exclusion from the CDC criteria is justified. A detailed review of the world literature reveals an increased awareness and diagnosis of this infection in patients with AIDS which takes the form of dissemination, a rapid course, and a usually fatal outcome.

Cytomegalovirus (CMV) encephalitis typically occurs as a diffuse cerebral infection in patients with advanced AIDS. This is a case report of a patient who presented with right-sided weakness and subsequently was found to have a cerebral mass lesion due to CMV. Only four similar cases are described in the literature. Though uncommon, CMV encephalitis must be considered in the differential diagnosis of cerebral mass lesions in patients with advanced AIDS.