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HIV caregivers face many challenges following initiation of ART. The development of jaundice is uncommon but worrisome. In this case, two distinct and contrasting episodes of jaundice were observed. In the first instance, isolated elevation of the indirect bilirubin without elevation of the alkaline phosphatase was noted. The normal PT and serum aminotransferase levels indicate the absence of intrinsic liver dysfunction. Elevations in the indirect bilirubin may result from either impaired uptake/conjugation or excess production. The latter, usually from acquired hemolysis, may be a complication of an occult NHL. A work-up for this AIDS-related malignancy was not initiated since the caregivers recognized jaundice as a complication of IDV, which inhibits UDP-glucuronyl transferase and produces a Gilbert's-like syndrome. Physicians can expect to encounter this syndrome even more frequently with ATV. Experienced patients given RTV-boosted ATV have experienced elevations of unconjugated hyper-bilirubinemia in up to 45 percent of cases in clinical trials. However, such elevations do not reflect liver dysfunction and symptomatic jaundice requiring dosage reduction that occurred infrequently (7 to 8 percent of study patients). Counseling patients about this syndrome may promote adherence and prevent self-directed interruptions of ATV that compromise efficacy. The second case of jaundice provides a more formidable diagnostic challenge. The triad of LFT abnormalities (mild elevation of aminotransferases, normal PT, and marked cholestatic jaundice) implies an acute process that is mildly toxic to hepatocytes without affecting their synthetic function. The subacute nature of the patient's cholestatic jaundice suggests either intrahepatic infiltrative disease of the liver or extrahepatic obstruction of the biliary tree, most likely due to the patient's relatively modest level of pain and lack of fever. Despite LFT abnormalities occurring 17 months after a switch in his ART, cumulative drug-related toxicities must still be considered. Ritonavir can produce significant elevations in the AST/ALT, especially with pre-existing chronic liver disease as with hepatitis C virus coinfection. The NRTIs can produce hepatic steatosis, a result of mitochondrial toxicity and impaired fatty acid oxidation. However, jaundice and cholestasis are not typical of the latter syndrome. With a negative contrast CT that excludes parenchymal liver disease, investigation of the biliary tree to assess the presence of AIDS-related cholangitis was the next step. Performing a sphincterotomy or stent placement, and obtaining brushings or biopsy specimens to determine the extent of extrahepatic obstruction may help define a pathogen and be life-saving. The negative results of the ERCP justify the final diagnostic step, a liver biopsy to evaluate microscopic infiltrative disease that might not have been detected on contrast abdominal CT. Examples might include granulomatous disease (MAC), fungal etiologies (histoplasmosis), carcinomatosis (lymphoma, hepatoma, cholangiocarcinoma), and microvascular disease (bacillary angiomatosis). The failure to observe granulomatous inflammation in the liver does not exclude MAC infection, as MAC may involve other peri-aortic or mesenteric lymph nodes. This form of IRIS is unlikely given the abdominal CT findings, lack of systemic complaints, and extended persistence of liver aminotransferases. The nonspecific results of the liver biopsy are a common outcome in advanced AIDS patients with elevated alkaline phosphatase levels. Despite not having identified a pathogen, the biopsy establishes chronic liver disease and prompts re-evaluation and change of treatment to NFV. The subsequent normalization of the patient's aminotransferase levels suggests a prior adverse effect of LPV/r in the setting of unexplained, chronic liver disease. Most importantly, this case highlights the importance of HIV caregivers to review ART for safety when noting chronic liver dysfunction. Patients need to be counseled to minimize acetaminophen use, to consume alcohol in moderation, and to avoid behavior with risk for hepatitis C. Finally, all HIV patients should receive appropriate vaccination against hepatitis A and B if serology shows lack of protective immunity.
J Int Assoc Physicians AIDS Care (Chic)
PMID:Clinical vignette in antiretroviral therapy: jaundice. 1498 14

Co-infection with HIV-1 and M. Leprae is a rare event in endemic areas for leprosy and HIV, such as India. Neither an increased HIV prevalence among leprosy cases, nor any rapid progression to AIDS was observed among dual HIV-leprosy infections. The current situation concerning continued new leprosy case-detection and gradual increase in HIV infection in India and a few other developing countries, such as Brazil, emphasizes the importance of monitoring the occurrence of co-infections. There is so far no change in the clinical spectrum of leprosy, PB/MB ratio, leprosy reactions and neuritis among co-infected patients. All types of leprosy occur in HIV patients [except in one study (Borgdorff et al, 1993) where more MB leprosy cases with HIV infection were seen]. Histopathological observations reveal a normal spectrum of appearance in biopsies of leprosy lesions from co-infected patients suggesting that cell-mediated immune response to M leprae is preserved at the site of the disease, despite evidence that these responses are abrogated systemically. All dual infection cases respond to regular treatment, except in three studies which noted more relapses. Therefore, a longer duration of surveillance is advisable after fixed duration therapy, for the detection of early relapse. Type 2 reaction can be managed with a higher dose of clofazimine. Type 1 reaction when developed as such, or as IRIS, needs oral steroids in adequate doses, particularly when associated with neuritis and motor loss, since lower doses may not be able to reverse the motor loss even of early onset. However, higher doses of corticosteroid when given need to be monitored closely. The impact of immune restoration in co-infected patients receiving ART is commonly observed in cases with borderline leprosy.
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PMID:Does concomitant hiv infection has any epidemiological, clinical, immunopathological and therapeutic relevance in leprosy? 1757 67

Cytomegalovirus (CMV) infection is a relatively late complication of AIDS. Like other viruses contributing to co-morbidity of HIV infection, cytomegalovirus has the propensity to cause multiorgan involvement. We report the case of a 34-year-old seropositive man who presented with bilateral lower limb weakness and symptomatic pallor. He was already on antiretroviral drugs for a month prior to presentation. Detailed clinical examination and laboratory investigations revealed cytomegalovirus polyradiculoneuropathy associated with bone marrow dysplasia. Dysplasia of haematopoeitic cell lines occurs in 30% to 70% of HIV infected patients, and is often indistinguishable from myelodysplastic syndrome. However, in our case, the bone marrow picture reverted back to normal with treatment of the CMV infection, pointing to a possible role of CMV as the causative agent of bone marrow dysplasia. Moreover, CMV has been incriminated as a pathogen producing the immune reconstitution inflammatory syndrome. The onset of the disease in our case one month after initiation of HAART strongly raises the possibility of this being a case of CMV related IRIS. This is the first reported case where IRIS has presented with CMV polyradiculoneuropathy and bone marrow dysplasia. We would like to highlight that in today's era of HIV care, clinicians should be aware of the possibility of multiorgan involvement by CMV, for appropriate management of this disease in the background of AIDS.
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PMID:Multiorgan involvement due to cytomegalovirus infection in AIDS. 1762 53

Immune reconstitution inflammatory syndrome is commonly seen in acquired immunodeficiency syndrome (AIDS) patients having concomitant opportunistic infection, following initiation of highly active anti-retroviral therapy (HAART). We describe IRIS in a young man with unknown human immunodeficiency virus (HIV) status who presented with cryptococcal lymphadenitis as the first manifestation of AIDS. At presentation the patient had features overlapping with tuberculosis (TB) lymphadenitis which was ruled out by fine needle aspiration cytology. The patient responded to antifungal treatment but following the start of HAART, symptoms recurred which were managed conservatively. Though TB is common in India, a thorough workup including histopathology of lymph node should be done before the patient is started on anti-tuberculosis treatment. HIV infected patients having opportunistic co-infection should be closely monitored following initiation of HAART.
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PMID:Immune reconstitution inflammatory syndrome in a patient with cryptococcal lymphadenitis as the first presentation of acquired immunodeficiency syndrome. 1809 14

Tremendous advances have occurred in the care of patients with HIV/AIDS resulting from the advent of highly active antiretroviral therapy (HAART). This has led to differences in the presentations of HIV-related pulmonary disease. Infections such as bacterial pneumonias, particularly Streptococcus pneumoniae, remain commonplace, while opportunistic agents such as Pneumocystis jirovecii remain a concern in patients without adequate access to optimal medical care. The tuberculosis epidemic, once thought to be slowing, has been re-energized by the spread of HIV, particularly in sub-Saharan Africa. Unusual inflammatory responses due to a phenomenon of immune reconstitution, are now recognized as a consequence of HAART, with a reported incidence of IRIS in this setting ranges from 7 to 45% in retrospective reviews. Noninfectious pulmonary conditions such as chronic obstructive lung disease and pulmonary malignancies are gaining prominence as patients are accessing antiretroviral care and enjoying significantly extended survival.
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PMID:Changing global epidemiology of pulmonary manifestations of HIV/AIDS. 1905 59

This study analyzes immunologic markers to predict and diagnose tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV and TB coinfected adults who initiated antiretroviral therapy (ART) in Thailand. T helper 1 cytokines interleukin (IL)-2, IL-12, and interferon-gamma (IFN-gamma) levels in response to PPD and RD1 antigens were assessed prior to ART, at weeks 6, 12, and 24 of treatment, and at time of TB-IRIS. Of 126 subjects, 22 (17.5%) developed TB-IRIS; 14 (64%) subjects received steroid treatment and 3 (14%) received NSAIDs; none of the subjects died. Median interval between ART initiation and TB-IRIS development was 14 days. IFN-gamma, IL-2, and IL-12 responses did not differ between TB-IRIS and no TB-IRIS subjects (p > 0.05). More research into the immunopathogenesis of TB-IRIS and diagnostic potential of cytokine markers is warranted.
AIDS Res Hum Retroviruses 2009 Nov
PMID:Immunologic markers as predictors of tuberculosis-associated immune reconstitution inflammatory syndrome in HIV and tuberculosis coinfected persons in Thailand. 1988 38

Fixed dose combination abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) among HIV-1 and tuberculosis (TB)-coinfected patients was evaluated and outcomes between early vs. delayed initiation were compared. In a randomized, pilot study conducted in the Kilimanjaro Region of Tanzania, HIV-infected inpatients with smear-positive TB and total lymphocyte count <1200/mm(3) were randomized to initiate ABC/3TC/ZDV either 2 (early) or 8 (delayed) weeks after commencing antituberculosis therapy and were followed for 104 weeks. Of 94 patients screened, 70 enrolled (41% female, median CD4 count 103 cells/mm(3)), and 33 in each group completed 104 weeks. Two deaths and 12 serious adverse events (SAEs) were observed in the early arm vs. one death, one clinical failure, and seven SAEs in the delayed arm (p = 0.6012 for time to first grade 3/4 event, SAE, or death). CD4 cell increases were +331 and +328 cells/mm(3), respectively. TB-immune reconstitution inflammatory syndromes (TB-IRIS) were not observed in any subject. Using intent-to-treat (ITT), missing = failure analyses, 74% (26/35) vs. 89% (31/35) randomized to early vs. delayed therapy had HIV RNA levels <400 copies/ml at 104 weeks (p = 0.2182) and 66% (23/35) vs. 74% (26/35), respectively, had HIV RNA levels <50 copies/ml (p = 0.6026). In an analysis in which switches from ABC/3TC/ZDV = failure, those receiving early therapy were less likely to be suppressed to <400 copies/ml [60% (21/35) vs. 86% (30/35), p = 0.030]. TB-IRIS was not observed among the 70 coinfected subjects beginning antiretroviral treatment. ABC/3TC/ZDV was well tolerated and resulted in steady immunologic improvement. Rates of virologic suppression were similar between early and delayed treatment strategies with triple nucleoside regimens when substitutions were allowed.
AIDS Res Hum Retroviruses 2009 Dec
PMID:Early versus delayed fixed dose combination abacavir/lamivudine/zidovudine in patients with HIV and tuberculosis in Tanzania. 2000 18

Since its initial description, there have been significant changes in the epidemiology, pathogenesis, and clinical and imaging manifestations of JCV infection of brain. The most common clinical manifestation is PML. Other recently described CNS manifestations are JCE, JCVGCN, and JCM. Although AIDS is the most common predisposing factor for JCV reactivation, there is increasing incidence of brain manifestations of JCV reactivation in non-HIV settings, including different rheumatologic, hematologic, and oncologic conditions; monoclonal antibody therapy; transplant recipients; primary immunodeficiency syndromes; and even in patients without any recognizable immune deficiency. IRIS may develop secondary to restoration of immunity in HIV-positive patients with PML receiving antiretroviral therapy. This is of profound clinical significance and needs to be diagnosed promptly. Imaging plays a crucial role in the diagnosis of the disease, monitoring of treatment response, identifying disease progression, and predicting prognosis. In this article, current understanding of the epidemiology, pathogenesis, clinical presentations, and all aspects of imaging of JCV infection of the brain have been comprehensively reviewed.
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PMID:JC virus infection of the brain. 2053 29

Immune Reconstitution syndrome following antiretroviral therapy is common in HIV/AIDS patients due to boosting of immunity. A case is reported here wherein AIDS-related Non-Hodgkin's lymphoma patient received CHOP regimen and antiretroviral therapy. Patient developed tubercular lymphadenopathy paradoxically as a manifestation of IRIS.
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PMID:Immune reconstitution inflammatory syndrome in AIDS-related non-hodgkin's lymphoma. 2083 62

We report an unusual case of HIV-related immune reconstitution inflammatory syndrome, presenting as suspected AIDS-related lymphoma. Symptoms, initial investigations including fine-needle biopsy and 18F-FDG PET/CT scan were highly compatible with high grade AIDS-related lymphoma, however subsequently IRIS was diagnosed. We discuss pitfalls in the interpretation of diagnostic results in ARL versus IRIS.
AIDS Res Ther 2011 Sep 28
PMID:Immune reconstitution syndrome presenting as probable AIDS-related lymphoma: a case report. 2195 17


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