AIDS-defining Opportunistic Infection Research Articles

Spectrum of AIDS Defining Opportunistic Infections in a Series of 77 Hospitalised HIV-Infected Omani Patients

Most of the morbidity and mortality in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) result from opportunistic infections (OIs). Although the spectrum of OIs in HIV infected patients from developing countries has been reported, there is a paucity of data on the natural history, pattern of disease, and survival of hospitalised patients with HIV/AIDS, particularly in Arab countries. The aim of this study was to study retrospectively the spectrum and frequency of various OIs in a cohort of hospitalised HIV-infected Omani patients. Included in the study were 77 HIV-infected Omani patients admitted to a tertiary care teaching hospital in Muscat, Oman, between January 1999 and December 2008. They were diagnosed on their first admission and hence were not on highly active antiretroviral therapy (HAART) at presentation. The frequency of various clinical and laboratory findings and individual OIs were analysed. In total, 45 patients (58%) had one or more AIDS-defining OIs. Pneumocystis jiroveci pneumonia (PCP) was commonest (25%), followed by cryptococcal meningitis (22%), cytomegalovirus (CMV), retinitis (17%), disseminated tuberculosis (15%), and cerebral toxoplasmosis (12.5%). Only one patient with Mycobacterium avium-intracellulare (MAI) was identified and one patient had disseminated visceral leishmaniasis. The majority of patients (77%) had CD4+ counts <200 cells/μL. Ten patients (22%) died during hospital stays, with five deaths (50%) being caused by disseminated CMV infection. A wide spectrum of OIs is seen in hospitalised HIV-infected patients in Oman. P. jiroveci pneumonia and cryptococcal meningitis were the commonest OIs, while disseminated CMV was the commonest cause of death. We hope these results will advance the knowledge of specialists treating HIV in Oman and the Gulf region.

Circulating mediators of inflammation in AIDS-related non-Hodgkin lymphoma.

86 Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-related malignancy in developed countries, accounting for 3-6% of AIDS-defining illnesses and 23-30% of AIDS-related mortality. The risk of developing NHL is estimated to be 60 times greater in HIV-infected individuals in comparison to the general population and this rate has remained elevated despite the advent of HAART. The mechanisms underlying the development of AIDS-related NHL (A-NHL) are not fully understood, but likely involve persistent B-cell activation and inflammation. Methods: This was a nested case-control study within the ongoing prospective Multicenter AIDS Cohort Study (MACS). Cases included 47 HIV-positive male patients diagnosed with high-grade B-cell NHL. Controls were matched to each case from among those participants who developed an AIDS-defining opportunistic infection in the absence of any malignancy. Matching criteria included age and CD4+ cell count. Sera obtained from each patient near the time of NHL or AIDS diagnosis was tested for a panel of 171 serum biomarkers using multiplexed bead-based immunoassays. Biomarker measurements were evaluated to identify significant alterations between the experimental groups, correlations with disease progression and interactions between biomarkers. Results: A subset of 21 biomarkers was identified to be significantly altered in A-NHL cases in comparison to the AIDS controls. This subset included cytokines, chemokines, acute phase proteins, tissue remodeling agents and bone metabolic mediators. Many of the biomarkers included in this subset were positively correlated with disease progression. A pathway analysis of our results revealed an extensive network of interactions between current and previously identified biomarkers. Conclusions: These findings support the current hypothesis that A-NHL develops in response to persistent immune stimulation and inflammation. A network of inflammatory mediators was identified demonstrating correlations with disease progression and overexpression in A-NHL patients. Further analysis of these biomarkers should enhance our ability to diagnose, monitor, and treat this disease.

Free Light Chains and the Risk of AIDS-Defining Opportunistic Infections in HIV-Infected Individuals

The relevance of B-cell dysfunction for progression to AIDS among human immunodeficiency virus (HIV)-infected individuals has not been clearly defined. We evaluated the association between circulating κ and λ free light chains (FLCs), which are markers of B-cell dysfunction, and risk of developing an AIDS-defining opportunistic infection in HIV-infected men. The study included 252 case patients with clinical AIDS and 252 HIV-infected controls from the Multicenter Hemophilia Cohort Study I. Case patients were matched to controls on birth date, specimen type, blood sample collection date, and CD4 cell count. Levels of κ and λ FLCs were measured in serum or plasma collected 0-2.5 years before selection. Elevated FLC levels (κ or λ, above the upper limit of normal) were classified as polyclonal (normal κ-λ ratio) or monoclonal (abnormally skewed κ-λ ratio). We used conditional logistic regression to estimate odds ratios (ORs) for AIDS. FLC levels were higher in case patients than in controls, for κ (median, 4.03 vs 2.98 mg/dL) and λ (3.77 vs 2.42 mg/dL) FLCs. Compared with normal levels, above-normal FLC levels were associated with AIDS (OR, 3.13 [95% confidence interval (CI), 1.78-5.49] for κ and 3.47 [2.31-5.20] for λ FLCs), and the association with AIDS was strengthened with increasing κ and λ FLC levels (P trends < .0001). Polyclonal FLC elevation was associated with a 4-fold increase in the risk of AIDS (OR, 3.85; 95% CI, 1.97-7.54), but monoclonal FLC elevation was not associated with AIDS. Circulating FLCs are associated with elevated risk of AIDS in HIV-infected individuals. Polyclonal B-cell dysfunction may contribute to HIV-related immune suppression and predispose to clinical AIDS events.

Determinants of Late-Stage HIV Disease at Diagnosis in Singapore, 1996 to 2009

The delay in HIV diagnosis has been identified as a significant reason for late presentation to medical care. This research aims to elucidate the significant determinants of late-stage HIV infection in Singapore between 1996 and 2009, after the advent of highly active anti-retroviral therapies. We included 3735 patients infected via sexual mode of transmission from the National HIV Registry diagnosed between 1996 and 2009. Late-stage HIV infection is defined as CD4 count less than 200 mm(3) or AIDS-defining opportunistic infections at fi rst diagnosis or within one year of HIV diagnosis. We determined independent epidemiological risk factors for late-stage HIV infection at first diagnosis using multivariate logistic regression. Multivariate analysis showed that older age corresponded significantly with increasing odds of late-stage HIV infection. Compared to persons diagnosed at 15 to 24 years of age, those diagnosed at age 55 years and above were associated with 5-fold increased likelihood of late-stage infection (adjusted odds ratio (AOR): 5.17; 95% CI, 3.21 to 8.33). Chinese ethnicity, singlehood, and non-professional occupations were also significantly associated with late-stage HIV infection. Persons detected in the course of medical care had over 3.5 times the odds of late-stage infection (AOR: 3.55; 95% CI, 2.71 to 4.65). Heterosexual mode of transmission and having sex workers and social escorts as sexual partners, were the other epidemiological risk factors with significant associations. The findings of this study emphasises the need to increase HIV awareness and to encourage early and regular HIV testing among at-risk persons.

Histoplasmose: seltene opportunistische Infektion bei HIV-Infektion

A 19-year-old HIV-positive man was admitted with fever of unknown origin and poor general condition. Antiretroviral therapy had been stopped by the patient eight months prior to admission. Laboratory tests revealed pancytopenia, high viral load and low count of T-helper cells (13/µl). Computer tomography of the thorax showed small patchy infiltrations. Extensive examinations (microbiology, laboratory tests, multiple investigations) revealed no pathogen. Liver biopsy proved disseminated histoplasmosis. Liposomal amphotericin B was started and switched to oral itraconazole after 14 days with itraconazole. With this treatment the patient condition improved and fever stopped. T-helper cells increased and the patient was discharged. Disseminated histoplasmosis as an AIDS-defining opportunistic infection is uncommon (particularly as the patient had not been abroad in the last four years) and can be a life-threatening complication. Diagnosis must be confirmed by invasive methods especially in patients with compromised immune status and rapid clinical progression.

Paradoxical Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients Treated With Combination Antiretroviral Therapy After AIDS-Defining Opportunistic Infection

The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs. We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS. Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%-16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P < .01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4(+) cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53 cells/μL, P = .04, mucocutaneous KS; +261 vs +113, P = .04, tuberculosis). Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.

HIV/TB Coinfection + Low CD4-Cell Count = Start ART Sooner Rather Than Later

Although tuberculosis (TB) is the most common AIDS-defining opportunistic infection worldwide, the timing of antiretroviral therapy (ART) in

Neglected Fungal Diseases in Sub-Saharan Africa: A Call to Action

Despite the considerable morbidity and mortality associated with fungal diseases in sub-Saharan Africa, it is notable that these diseases have been omitted from an expanded list of neglected tropical diseases. Inextricably tied together with HIV/AIDS and tuberculosis in sub-Saharan Africa, important fungal diseases such as cryptococcal meningitis and Pneumocystis jirovecii pneumonia (PCP) manifest as relatively common and deadly AIDS-defining opportunistic infections, often masked by and comorbid with tuberculosis. Others, such as mycetoma, which manifest as a debilitating and deforming illness primarily affecting rural adults, directly affect the socioeconomic productivity of rural communities. Lack of adequate diagnostic tests makes identifying the true disease burden due to fungal diseases difficult. To highlight the devastating impact of fungal diseases on the health and socioeconomic circumstances of sub-Saharan Africa’s poorest people and to increase the profile of efforts to control and prevent these diseases, we propose that the following fungal diseases be added to the list of neglected tropical diseases: cryptococcal meningitis, PCP, mycetoma, histoplasmosis, sporotrichosis, and blastomycosis. By outlining the prevalence, distribution, and disease burden of these fungal diseases in sub-Saharan Africa in this review, we hope to provide information to prioritize strategies for detection, control, and prevention of the neglected fungal diseases.

Latinos and HIV Care in the Southeastern United States: New Challenges Complicating Longstanding Problems

In recent years, Hispanics/Latinos have become the largest immigrant group in the United States. Hispanics/Latinos represent the fastest growing minority group in the United States and have now surpassed 50 million, accounting for approximately 1 of 6 people living in the United States according to the most recent census data. The term ‘‘Latino or Hispanic’’ is applied to a very heterogeneous group from different countries and different cultures, and thus it is not possible to think of this population as a homogeneous group. Nevertheless, of the Hispanics living in the United States, almost 30 million are of Mexican origin. However, while Mexicans have been coming to the United States for centuries, the migration patterns have not remained the same. One relatively recent shift in Mexican immigration has been the places where Mexican immigrants have settled. Whereas traditionally they tended to remain primarily in border states that formerly belonged to Mexico, such as California, Arizona, or Texas, more recently they have increasingly gone to other areas, such as the Midwest and the Southeast, in large part as a result of employment opportunities. As a result, between 1990 and 2000, the Mexican immigrant population in the Southern states grew more than 300% [1]. Hispanics/Latinos as a group tend to have less education and English language proficiency and frequently lack health insurance. At 41.5%, Hispanics are the demographic segment of the adult population in the United States most likely to be uninsured. Another salient feature of Mexican immigrants living in the United States is that approximately half are undocumented and thus further marginalized from the health care system. Of the approximately 46 million uninsured individuals in the United States, about 20% are undocumented and most are Hispanics. Thus, it should come as no surprise that Hispanics/Latinos experience substantial health disparities, because their access to medical care is suboptimal and, when ill, they commonly present late for medical care [2]. Contrary to popular belief, however, undocumented immigrants have lower rates of health care utilization than do native-born Americans and only seek medical care in the United States when an illness worsens or when they have a life-threatening medical emergency [3]. The existing disparities affecting the Hispanic/Latino population in the United States are also present in human immunodeficiency virus (HIV) infection. The Centers for Disease Control and Prevention estimates that the rate of HIV infection among Hispanics is 2.5 times that of whites and that Hispanics are more likely to be ‘‘late HIV testers’’ [4]. In general, it has been shown that HIV disease is diagnosed at a later stage in Hispanics/Latinos and that these patients have lower CD4 cell counts, higher HIV RNA levels, more AIDS-defining opportunistic infections, and longer hospital stays than whites [5, 6]. Latinos have also been shown to have significant delays in initiation of HIV care. Reasons for delay of care include lack of access to transportation, being too sick to go to the doctor, and having 1 or more competing needs on expenditures, such as rent and food costs. The article by Dennis et al in this issue of Clinical Infectious Diseases documents some of the challenges in providing care for HIV-infected Latinos in North Carolina, a state that has experienced a recent and rapid increase in the Latino population [7]. Their findings are Received 19 May 2011; accepted 24 May 2011. Correspondence: Carlos del Rio, MD, Department of Global Health, Emory University Rollins School of Public Health, 1518 Clifton Rd, Rm 754, Atlanta, GA 30322 (cdelrio@emory.edu). Clinical Infectious Diseases 2011;53(5):488–489 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. 1058-4838/2011/535-0014$14.00 DOI: 10.1093/cid/cir440

Pulmonary histoplasmosis presenting as chronic productive cough, fever, and massive unilateral consolidation in a 15-year-old immune-competent boy: a case report

IntroductionSevere histoplasmosis is known to be among the AIDS-defining opportunistic infections affecting patients with very low CD4 cell counts in histoplasmosis-endemic areas. Histoplasma capsulatum var. duboisii is common in West and Central Africa, where it occurs in both HIV/AIDS and non-HIV patients. Few cases of life-threatening histoplasmosis in immune-competent individuals have been reported worldwide.Case reportWe describe a case of pulmonary histoplasmosis diagnosed on the basis of autopsy and histological investigations. A 15-year old East African immune-competent boy with a history of smear-positive tuberculosis and a two-year history of rock cutting presented to our hospital with chronic productive cough, fever, and massive unilateral consolidation. At the time of presentation to our hospital, this patient was empirically treated for recurrent tuberculosis without success, and he died on the seventh day after admission. The autopsy revealed a huge granulomatous lesion with caseation, but no acid-fast bacilli were detected on several Ziehl-Neelsen stains. However, periodic acid-Schiff staining was positive, and the histological examination revealed features suggestive of Histoplasma yeast cells.ConclusionSevere pulmonary histoplasmosis should be considered in evaluating immune-competent patients with risk factors for the disease who present with pulmonary symptoms mimicking tuberculosis.

HIV and Chronic Obstructive Pulmonary Disease: Is It Worse and Why?

Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting of HIV infection may increase the number of complications seen. Before the era of combination antiretroviral therapy, HIV-infected persons were noted to have an accelerated form of COPD, with significant emphysematous disease seen in individuals less than 40 years old. Unlike many of the AIDS-defining opportunistic infections, HIV-associated COPD may be more common in the current era of HIV because it is frequently reported in patients without a history of AIDS-related pulmonary complications and because many aging HIV-infected individuals have had a longer exposure to smoking and HIV. In this review, we document the epidemiology of HIV-associated COPD before and after the institution of combination antiretroviral therapy, review data suggesting that COPD is accelerated in those with HIV, and discuss possible mechanisms of HIV-associated COPD, including an increased susceptibility to chronic, latent infections; an aberrant inflammatory response; altered oxidant-antioxidant balance; increased apoptosis associated with HIV; and the effects of antiretroviral therapy.

Clinical Features, Treatment, and Outcome of Severe HIV-Associated Immune Thrombocytopenic Purpura In the HAART Era

AbstractAbstract 2522 Background:The association between HIV and immune thrombocytopenic purpura (ITP) is well documented. Although HIV-associated ITP responds both to highly active anti-retroviral therapy (HAART) and treatments used in classic ITP, the clinical features of HIV-associated ITP were documented prior to the widespread use of HAART, and there are currently no widely accepted guidelines for the management of HIV-associated ITP. Here we describe the clinical features, treatment, and outcomes of patients diagnosed with severe HIV-associated ITP in the HAART era. Methods:We searched the BC Centre for Excellence in HIV/AIDS (CFE) database to identify patients with ≥ 1 platelet count <20 × 109/L since January 1996, the year HAART was widely adopted in British Columbia. The cutoff value of <20 × 109/L was chosen as a clinically relevant platelet count since these patients generally require treatment. Patient charts were reviewed, clinical data extracted, and only patients with a diagnosis of ITP made by a hematologist were included in the analysis. Descriptive statistics were used to summarize the data. Results:Of 8922 patients in the CFE database since 1996, 31 (0.3%) with a diagnosis of ITP and a platelet count <20 × 109/L were identified. The median age at ITP diagnosis was 37 (range 27–66) years and 25 (81%) were male. The median platelet count was 6 (2-19) × 109/L and median hemoglobin 129 (34-165) g/L. Eighteen patients (51%) presented with clinical bleeding and 4 (13%) required packed red blood cell transfusion. Sixteen (62%) of 26 patients with a documented HIV risk factor had a history of injection drug use (IDU). Four patients (13%) were coinfected with the hepatitis B virus and 12 (39%) with hepatitis C. At ITP diagnosis, 8 of 29 patients (28%) had a CD4 count <200 cells/mL and the median CD4 was 290 (20-600) cells/mL; 5 had a prior AIDS-defining opportunistic infection or neoplasm. Although 29 patients received antiretrovirals at some point, only 10 (32%) were receiving HAART at ITP diagnosis. A bone marrow aspirate and biopsy was performed in 6 patients (19%) and was consistent with ITP in all. Initial ITP treatment included: IVIG, n=12; steroids, n=10; anti-RhD, n=8; HAART, n=3. The median number of treatments received was 1 (0-3) and median time to a platelet count >20 × 109/L was 13.5 (1-1379) days. Median platelet response within 30 days was 58 (5-322) × 109/L (n=26) but only 3 patients (10%) achieved a platelet count in the normal range. At a median follow-up of 48 (0.2-138) months, 27 patients (87%) required secondary ITP treatment for a recurrent platelet count <20 × 109/L; median 10 (5-20) × 109/L, including 8 of 13 patients receiving HAART with initial ITP therapy. Secondary ITP treatment included: IVIG, n=9; anti-RhD, n=6; steroids, n=4; splenectomy, n=3; danazol, n=1; and HAART, n=1. Median platelet response to secondary treatment was 42 (21-198) × 109/L. Response to ITP treatment was not significantly associated with treatment received but was lower in the following patients: 4/15 with comorbidities (5 related to the liver) vs 10/16 without; 1/21 IDU vs 4/10 with sexual HIV risk; and 4/13 with hepatitis B or C coinfection vs 13/16 without (p<0.05 for all). Complications of ITP treatment occurred in 2 patients: psychiatric effect of steroids, n=1; and post-splenectomy fever and hematoma, n=1. There were 4 deaths, causes were: GI bleed, n=2; Evan's syndrome and hepatic failure, n=1; advanced HIV, n=1. Of the 4 patients that died, 3 had a history of IDU. Comorbidities in patients who died included: hepatitis C, n=3; hepatic cirrhosis, n=2; portal hypertension, n=1; hepatocellular failure, n=1. One patient who died of GI bleeding had a history of IDU, hepatitis C coinfection, and died of variceal bleeding despite a normal platelet count following splenectomy. Conclusions:Most patients with severe HIV-associated ITP diagnosed in the HAART era achieved a safe platelet count with primary ITP treatment and there were few treatment complications. However, nearly all required retreatment for severe ITP, including 8 of 13 patients receiving HAART with initial ITP therapy. Inferior platelet response was associated with a history of IDU, comorbidities, and hepatitis B or C coinfection, and 3 of 4 deaths occurred in patients with a history of IDU, therefore new approaches to the treatment of severe ITP in this patient population are needed. This is to our knowledge the largest series of HIV-associated ITP reported in the era of HAART. Disclosures:No relevant conflicts of interest to declare.

Trends in Diseases Reported on US Death Certificates That Mentioned HIV Infection, 1996-2006

We examined trends during 1996-2006 in diseases reported on death certificates that mentioned HIV infection. We analyzed multiple-cause mortality data compiled from all US death certificates with any mention of HIV to determine the annual percentages of deaths with various diseases. Deaths reported with HIV during 1996-2006 decreased from 35 340 to 13 750. Standardized percentages of death certificates reporting AIDS-defining opportunistic infections also decreased: pneumocytosis (6.3% to 5.1%), nontuberculous mycobacteriosis (5.5% to 1.8%), cytomegalovirus (5.7% to 1.2%). Non-Hodgkin's lymphoma rose from 4.8% in 1996 to 6.4% in 1997 and declined to 5.0% in 2001, while Kaposi's sarcoma declined from 3.7% in 1996 to 1.7% in 2001; these AIDS-defining cancers had stable percentages after 2001. All other cancers increased during 1996-2006 (2.7% to 7.3%). The percentage of deaths with diseases not specifically attributable to HIV increased: liver disease (5.8% to 13.0%), kidney disease (7.9% to 12.0%), and heart disease (4.9% to 10.2%). Among deaths reported with HIV, the percentages reported with HIV-attributable diseases decreased, while the percentages reported with other diseases increased. Consequently, these other life-threatening diseases need more attention in the management of HIV-infected persons.

Paracoccidioidomycosis in Patients Infected with and Not Infected with Human Immunodeficiency Virus: A Case-Control Study

Epidemiologic and clinical data for 53 patients with paracoccidioidomycosis and co-infected with human immunodeficiency virus (HIV) (cases) were compared with those for 106 patients with endemic paracoccidioidomycosis (controls). The prevalence of Paracoccidioides brasiliensis co-infection was estimated in 1.4% in cases of acquired immunodeficiency syndrome (AIDS). Patients co-infected with HIV were younger, less involved in agricultural occupations; 83.7% had CD4+ cell count < 200 cells/microL. Paracoccidioidomycosis in co-infected patients usually showed a rapid progression, with more fever, frequent involvement of the lungs, and multiple extrapulmonary lesions. The response to antifungal therapy and deaths caused by paracoccidioidomycosis were similar in the two patient groups, but late relapses were more common in co-infected cases. Paracoccidioidomycosis in HIV-infected patients shows epidemiologic and clinical characteristics differing from those of the endemic disease and should be considered an AIDS-defining opportunistic infection in Latin America.

Role of collagen deposition in lymphatic tissues and immune reconstruction during HIV-1 and SIV infections

The hallmark of HIV-1/simian immunodeficiency virus infections is the progressive depletion of CD4(+) T cells that ultimately renders the host incapable of defending against AIDS-defining opportunistic infections and malignancies. Although many potential mechanisms have been proposed to explain CD4(+) T-cell loss, this review focuses on the growing evidence that collagen deposition and consequent fibrotic damage to the lymphatic tissue T-cell compartment contributes to CD4(+) T-cell decline and limits CD4(+) T-cell repopulation, even with highly active antiretroviral therapy.

Diffuse cutaneous leishmaniasis associated with the immune reconstitution inflammatory syndrome

Leishmaniasis is an emerging disease in HIV-infected persons; visceral leishmaniasis is an AIDS-defining opportunistic infection. The parasite that causes this infection is usually transmitted by the sandfly and occasionally by nonsterile needles among intravenous drug users. Diffuse cutaneous leishmaniasis (DCL) is a rare anergic variant of leishmanial infection with the characteristic presentation of numerous nonulcerating nodules with an abundant parasite load, lack of visceral involvement, negative reaction to the leishmanin skin test, and a chronic course with incomplete response to treatment and frequent relapses. We report a case of DCL that developed in the context of the immune reconstitution inflammatory syndrome (IRIS) in a man with AIDS following initiation of antiretroviral therapy. We also review DCL to emphasize the importance of recognizing and treating this evolving disease in the growing population of patients on immunorestorative therapy.

Effect of age and HAART regimen on clinical response in an urban cohort of HIV-infected individuals

The prevalence of HIV infection in older patients (> or =50 years) is increasing due to HAART, and new HIV infections in older patients. Some earlier studies suggest that older patients respond differently to HAART than younger patients. The objective of this study is to compare the effectiveness of HAART in older and younger HIV patients. Retrospective analysis of an observational clinical cohort. Virologic and immunologic response, progression to AIDS and mortality were compared between 670 younger patients (<40 years) and 149 older patients (> or =50 years) by t-test, Kaplan-Meier methods, and multivariate Cox proportional hazards analysis. Compared with younger patients, older patients were more likely to be on nonnucleoside reverse transcriptase inhibitors based versus protease inhibitor based regimens (42 vs. 29%, P < 0.01). Time to HIV-1 RNA virologic suppression was less in older than in younger patients (3.2 vs. 4.4 months, P < 0.01). Immunologic response did not differ by age. Older patients had fewer AIDS-defining opportunistic infections (22 vs. 31%, P < 0.01), but higher mortality (36 vs. 27%, P = 0.04) and shorter survival (25th percentile survivor function 36.2 vs. 58.5 months, P = 0.02) than younger patients. Older age was associated with more rapid virologic suppression [adjusted hazard ratio = 1.33 (1.09-1.63)] and earlier mortality [adjusted hazard ratio = 1.56 (1.14-2.14)]. Nonnucleoside reverse transcriptase inhibitors based regimens were associated with more rapid virologic suppression [adjusted hazard ratio = 1.22 (1.03-1.44)]. Time to virologic suppression after HAART initiation was shorter in older patients, although CD4 response did not differ by age. Older patients had fewer opportunistic infections, but survival was shorter. Our data suggest a need to better understand causes of mortality in older patients.

Why is HIV a pathogen?

The pathogenesis of HIV begins with a profound depletion of CD4+ T cells in the gut followed by a long period of clinically silent but dynamic virus replication and diversification with high host cell turnover before the onset of AIDS. The AIDS-defining opportunistic infections and tumors mark the end-point of a long balancing act between virus and host that occurs when CD4+ T cell numbers fall below a level that can sustain immunity. Comparative studies of lentivirus infections in other species show that AIDS is not an inevitable outcome of infection because simian immunodeficiency virus in natural hosts seldom causes disease. What distinguishes pathogenic from 'passenger' infection is a systemic activation of immune responses followed by destruction of the integrity of lymphoid follicles. Macrophage and dendritic cell infection also contribute to pathogenesis. Maedi-Visna virus infection in sheep, which targets these cells but not T lymphocytes, also leads to progressive disease and death that resembles the wasting and brain diseases of HIV without the T cell immunodeficiency. Thus, lessons from pathogenic and nonpathogenic lentivirus infections provide insight into the complex syndrome called AIDS.

Coping with the HIV epidemic 1982–2007: 25‐year outcomes of the Hershey Haemophilia Cohort

Coping with the HIV epidemic 1982–2007: 25‐year outcomes of the Hershey Haemophilia Cohort

British HIV Association guidelines for HIV‐associated malignancies 2008

British HIV Association guidelines for HIV‐associated malignancies 2008