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Purpose of Review: This article intends to briefly discuss AIDS, summarize the current literature on immune recovery uveitis, describe its ocular manifestations and complications, and tackle its complex management., Recent Findings: The clinical picture of immune recovery uveitis is still evolving. Up to today, there are still no definite criteria for immune recovery uveitis, and although closely associated with cytomegalovirus retinitis and HIV/AIDS, there are several cases of similar intraocular response in non-HIV patients. The exact pathology for this paradoxical inflammatory reaction remains unclear; however, there is an interest in identifying biomarkers to determine underlying mechanisms and identify patients at risk. The management of this disease also remains a challenge and no standardized treatment approach exists currently., Summary: Immune recovery uveitis is an important cause of visual morbidity particularly in HIV/AIDS patients receiving highly active antiretroviral. It is a paradoxical reaction that is frequently associated with a prior cytomegalovirus retinitis infection. Although it can be a transient and self-limiting process, there is a complex decision on the timing of antiviral treatment and the initiation of antiretroviral treatment to prevent immune recovery uveitis. Furthermore, a substantial challenge arises in balancingtreatment decisions for complications in refractory cases., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors declare no conflicts of interest.

Objectives: We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories., Methods: The following diagnostic techniques were analyzed in 24 months (2017-2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests., Results: A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89-95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89-96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3-98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen., Conclusion: Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices.

Background: Toxoplasma encephalitis (TE) is one of the main opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients, and represents a social burden due to its high prevalence and morbidity. Concomitant antiretroviral therapy (ART), together with effective anti- toxoplasma combination therapy, is an effective strategy to treat AIDS-associated TE (AIDS/TE) patients. However, the timing for the initiation of ART after diagnosis of TE remains controversial. We therefore designed the present study to determine the optimal timing for ART initiation in AIDS/TE patients., Methods/design: This trial is a 17-center, randomized, prospective clinical study with 2 parallel arms. A total of 200 participants will be randomized at a 1:1 ratio into the 2 arms: the early ART initiation (≤14 days after TE diagnosis) arm and the deferred ART (>14 days after TE diagnosis) arm. The primary outcome will be the difference of mortality between the 2 arms at 48 weeks. The secondary outcomes will be the differences between the 2 arms in the changes of CD4+ counts from baseline to week 48, the rate of virologic suppression (HIV ribonucleic acid <50 copies/mL) from baseline to week 48, the incidence of TE-associated immune reconstitution inflammatory syndrome during the study period, and the incidence of adverse effects during the study period., Discussion: This present trial aims to evaluate the optimal timing for ART initiation in AIDS/TE patients, and will provide strong evidence for AIDS/TE treatment should it be successful., Trial Registration: This trial was registered as one of the 12 trials under the name of a general project at the chictr.gov (http://www.chictr.org.cn/showproj.aspx?proj=35362) on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.

Purpose of Review: More than two billion people are infected with Mycobacterium tuberculosis and few of them are ever offered therapy in spite of such treatment being associated with reduced rates of morbidity and mortality. This article reviews the current recommendations on the diagnosis and treatment of TB infection (or what is commonly referred to as 'prophylaxis' or 'preventive therapy' of latent TB) and discusses barriers to implementation that have led to low demand for this life-saving therapeutic intervention., Recent Findings: Treatment of infection for both TB and drug-resistant TB is well tolerated and effective, and several new, shorter regimens - including rfiapenitine-based regimens of 1 month and 12 weeks duration - have been shown to be effective. Not all persons infected with TB go on to develop disease and the risk is the highest in the first 2 years after infection. Given this, additional work is needed to better identify those at the highest risk of developing active TB., Summary: Practitioners should offer newer, shorter regimens to persons who are infected with TB and at high risk of developing disease, including people living with HIV and household contacts of people living with TB who are age 5 years and under. This includes individuals who have been exposed to drug-resistant forms of disease. Socioeconomic risk factors may play a key role in the development of TB disease and should also be addressed.

Cryptococcal meningiti s causes 15% of AIDS-related deaths globally. Screening and preemptive treatment for cryptococcal antigen (CrAg) in the blood of persons with advanced HIV/AIDS reduces mortality. National and international HIV guidelines recommend CrAg screening; however, implementation studies and evaluations of how to integrate CrAg screening programs into existing HIV care infrastructure are lacking.During a CrAg screening program in Kampala, Uganda, we interviewed 15 health care workers (2 coordinating research nurses and 13 clinic personnel) from 6 HIV clinics between March and April 2017, to identify barriers to implementation as well as facilitating factors for program success. The interviews were coded and themes compiled.We found key factors for successful implementation of a CrAg screening program were: adequate supplies of fluconazole and CrAg lateral flow assay (LFA) point-of-care tests, timely patient follow-up, and quick turnaround time of laboratory results. Although both CrAg LFA kits and fluconazole are on the national formulary, stockouts are common, affecting patient care. The CrAg screening recommendation by national HIV guidelines remains integral to the success of the program, as overburdened clinics are otherwise reluctant to adopt additional screening. Collaboration with Ministries of Health for support with enforcing national guidelines, and procuring supplies is paramount to a successful CrAg screening program.Development of a CrAg screening and treatment program within the HIV clinic infrastructure has a number of barriers. Education and training of clinic staff, along with partnership with the Ministry of Health to ensure adequate supplies, facilitated the program.

Purpose of Review: As HIV treatment programmes scale up to meet the UNAIDS 90-90-90 goals, care must be taken to start antiretroviral treatment safely in patients with advanced disease (CD4 counts <200 cells/μl) who are simultaneously at risk for opportunistic infections and immune reconstitution inflammatory syndrome. Invasive fungal diseases pose a great threat at this critical time point, though the development of inexpensive and highly accurate rapid diagnostic tests has changed the approach HIV programmes are taking to reduce the high mortality associated with these opportunistic infections. This article summarizes recent advances and findings in fungal opportunistic infection diagnostics with a focus on screening to prevent cryptococcal meningitis., Recent Findings: Cryptococcal antigen (CrAg) screening using a lateral flow assay platform is cost-effective and feasible to implement as either a laboratory reflex or point-of-care test. Recent CrAg screening pilots have elucidated the varying prevalence of cryptococcal antigenemia across geographic regions, which may aid programme planning. Evidence from recently completed clinical trials provides a strong motivation for the use of CrAg titer to refine treatment options for patients with subclinical cryptococcal disease., Summary: Although several operational barriers to programme effectiveness still need to be addressed, the utility of CrAg screening using inexpensive and accurate antigen assays has been demonstrated in real-world HIV programmes, paving the way for development and testing of other fungal opportunistic infection screening strategies and for an integrated advanced HIV disease testing package to reduce AIDS mortality and ensure safe antiretroviral treatment initiation.

Purpose of Review: Tuberculosis (TB) incidence has declined ∼1.5% annually since 2000, but continued to affect 10.4 million individuals in 2015, with 1/3 remaining undiagnosed or underreported. The diagnosis of TB among those co-infected with HIV is challenging as TB remains the leading cause of death in such individuals. Accurate and rapid diagnosis of active TB will avert mortality in both adults and children, reduce transmission, and assist in timeous decisions for antiretroviral therapy initiation. This review describes advances in diagnosing TB, especially among HIV co-infected individuals, highlights national program's uptake, and impact on patient care., Recent Findings: The TB diagnostic landscape has been transformed over the last 5 years. Molecular diagnostics such as Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis (MTB) resistance to rifampicin, has revolutionized TB control programs. WHO endorsed the use of Xpert MTB/RIF in 2010 for use in HIV/TB co-infected patients, and later in 2013 for use as the initial diagnostic test for all adults and children with signs and symptoms of pulmonary TB. Line probe assays (LPAs) are recommended for the detection of rifampicin and isoniazid resistance in sputum smear-positive specimens and mycobacterial cultures. A second-line line probe assay has been recommended for the diagnosis of extensively drug-resistant (XDR)-TB Assays such as the urine lateral flow (LF)-lipoarabinomannan (LAM), can be used at the point of care (POC) and have a niche role to supplement the diagnosis of TB in seriously ill HIV-infected, hospitalized patients with low CD4 cell counts of less than 100 cells/μl. Polyvalent platforms such as the m2000 (Abbott Molecular) and GeneXpert (Cepheid) offer potential for integration of HIV and TB testing services. While the Research and Development (R&D) pipeline appears to be rich at first glance, there are actually few leads for true POC tests that would allow for earlier TB diagnosis or rapid, comprehensive drug susceptibility testing, especially when considering the very high attrition rates observed between biomarker discovery and product market entry., Summary: In this review, we describe diagnostic strategies specifically for HIV and TB co-infected individuals. Molecular diagnostics in particular within the past 5 years have revolutionized and 'disrupted' this field. They lend themselves to integration of services with platforms capable of polyvalent testing. Impact on patient care is, however, still debatable. What has been highlighted is the need for health system strengthening and for true POC testing that can be used in active case finding.

Purpose of Review: Diagnosis and management of tuberculosis (TB) remains challenging and complex because of the heterogeneity of disease presentations. Despite effective treatment, TB disease can lead to significant short-and long-term health consequences. We review potential acute and chronic complications of TB disease and current management approaches., Recent Findings: Acute and subacute complications of TB disease are attributable to structural damage or vascular compromise caused by Mycobacterium tuberculosis, as well as metabolic abnormalities and host inflammatory responses. TB-related sepsis is a life-threatening acute complication for which current diagnostic and management approaches are likely inadequate. Therapeutic intensification and usage of immunomodulators are areas of ongoing research. Paradoxical reaction or symptom worsening during TB treatment may benefit from corticosteroids. Despite successful cure of TB, chronic complications can arise from anatomic alterations at disease sites. Examples include mycetomas developing within residual TB cavities, impaired pulmonary function, or focal neurologic deficits from tuberculomas., Summary: Effective management of TB requires attention to potential structural, metabolic, vascular, and infectious complications. In some instances, individualizing treatment regimens may be necessary. Imunosuppression and other host factors predispose to complications; others occur despite adequate treatment. Public health TB programs and health systems require additional resources to provide comprehensive TB and post-TB care.

Neurologic disease in acquired immunodeficiency syndrome (AIDS) patients is related either to opportunistic pathogens or to direct central nervous system (CNS) invasion by the human immunodeficiency virus. Despite the increasing availability of antiretroviral therapy, opportunistic infections continue to afflict patients in the developing world and in other populations with limited access to appropriate treatment. Classic CNS infections in the setting of AIDS include toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, and cytomegalovirus encephalitis. Additionally, AIDS patients are far more susceptible to acquiring CNS tuberculosis and neurosyphilis, both of which exhibit altered disease characteristics in the setting of immunosuppression. Neuroimaging is a crucial component of the diagnostic work-up of these conditions, and findings include, but are not limited to, intracranial mass lesions, white matter disease, meningoencephalitis, vascular complications, and hydrocephalus. Though various disease processes can produce imaging findings that overlap with one another, certain characteristic patterns may suggest a particular pathogen, and advanced imaging techniques and laboratory tests allow for definitive diagnosis. Knowledge of the imaging patterns seen in the setting of AIDS-related CNS disease is vital to the neuroradiologist, whose interpretation may guide decisions related to treatment and further work-up.

Purpose: To describe the appearance of acute syphilitic posterior placoid chorioretinitis, a rare ocular manifestation of syphilis, on spectral domain optical coherence tomography (SD OCT) both before and after treatment., Methods: Ophthalmic examination and imaging studies of 30 eyes of 19 confirmed cases were analyzed both at the time of presentation and at each follow-up visit. Patients with SD OCT and fluorescein angiography at the time of presentation, and at least three documented follow-up visits after initiation of therapy, were included in the study. Standard treatment of neurosyphilis was given to each patient, including 4 million units of penicillin G administered intravenously every 4 hours for 14 days., Results: Fundus examination and imaging studies were consistent with previous reports and confirmed the diagnosis of acute syphilitic posterior placoid chorioretinitis. In 13 eyes (43.3%), baseline SD OCT scans were performed within 1 to 2 days of presentation and revealed a small amount of subretinal fluid, disruption of the inner segment/outer segment junction, and hyperreflective thickening of the retinal pigment epithelium (RPE). All 30 eyes were again scanned between Days 7 and 9 after presentation and revealed loss of the inner segment/outer segment and OS/RPE bands, and irregular hyperreflectivity of the RPE with prominent nodular elevations but without subretinal fluid. Early disruption of the external limiting membrane and punctate choroidal hyperreflectivity were seen in 1 of the 30 eyes (3.3%) and 14 of the 30 eyes (46.6%), respectively. Vision improved and the outer retinal abnormalities normalized in 28 of the 30 eyes (93.3%) after the treatment of neurosyphilis. The external limiting membrane, inner segment/outer segment band, and/or linear outer segment/RPE junction remained substantially abnormal despite treatment in 2 eyes left with 20/200 vision., Conclusion: Patients with acute syphilitic posterior placoid chorioretinitis show characteristic outer retinal abnormalities on SD OCT imaging, including disruption of the inner segment/outer segment band, nodular thickening of the RPE with loss of the linear outer segment/RPE junction, and, in some cases, loss of the external limiting membrane, accumulation of subretinal fluid, and punctate hyperreflectivity in the choroid. Vision improved and these abnormalities reversed after treatment of neurosyphilis in most of the patients. Persistently, poor vision despite treatment was associated with long-term loss or disruption of outer retinal anatomy on SD OCT.

Objective: Although antiretroviral treatment (ART) has reduced the incidence of HIV-related opportunistic infections among children living with HIV, access to ART remains limited for children, especially in resource-limited settings. This paper reviews current knowledge on the contribution of opportunistic infections and common childhood illnesses to morbidity and mortality in children living with HIV, highlights interventions known to improve the health of children, and identifies research gaps for further exploration., Design and Methods: Literature review of peer-reviewed articles and abstracts combined with expert opinion and operational experience., Results: Morbidity and mortality due to opportunistic infections has decreased in both developed and resource-limited countries. However, the burden of HIV-related infections remains high, especially in sub-Saharan Africa, where the majority of HIV-infected children live. Limitations in diagnostic capacity in resource-limited settings have resulted in a relative paucity of data on opportunistic infections in children. Additionally, the reliance on clinical diagnosis means that opportunistic infections are often confused with common childhood illnesseswhich also contribute to excess morbidity and mortality in these children. Although several preventive interventions have been shown to decrease opportunistic infection-related mortality, implementation of many of these interventions remains inconsistent., Conclusions: In order to reduce opportunistic infection-related mortality, early ART must be expanded, training for front-line clinicians must be improved, and additional research is needed to improve screening and diagnostic algorithms.

Purpose of Review: Using the evidence published over the last 2 years, this review discusses the epidemiology, diagnosis, treatment and prevention of HIV-related pulmonary infections other than mycobacterial disease., Recent Findings: Longstanding, vertically acquired and apparently stable HIV infection is associated with significant and symptomatic small airways disease in African adolescents. The use of population-based pneumococcal vaccination in children is changing the severity and serotypes associated with HIV-related pneumococcal disease. Data on the use of blood 1,3,β-D-glucan show it has promise as a rule-out test for Pneumocystis pneumonia (PCP)., Summary: With widespread antiretroviral medication usage, the pattern of HIV-associated pulmonary disease is changing. Whereas opportunistic infections such as PCP still occur in people not using antiretroviral therapy (ART), HIV-related infections are similar to those present in the general population. Chronic lung disease is more prevalent, leading to its own infectious complications. The use of specific immunizations against infections is important, though their precise benefit with concomitant widespread ART and population-based vaccination programmes in the non-HIV community is undetermined.

Purpose of Review: This review summarizes the recent literature on the developments in diagnostics for pulmonary tuberculosis (TB)., Recent Findings: A growing body of literature regarding the Xpert MTB/RIF assay confirms the high diagnostic accuracy in a range of clinical settings, including amongst inpatients, those with HIV coinfection and in children with culture-positive disease. Early experiences with operational implementation are now being reported from South Africa. Initial small-scale evaluations suggest that newer versions of line-probe assays have diagnostic accuracy similar to that of the Xpert MTB/RIF assay. Next-generation fully automated molecular assays that use isothermal amplification may in the future be more readily implemented at the point of care. The first low-cost, lateral-flow (strip-test) assay for lipoarabinomannan in urine shows promise as a rapid point-of-care test for TB amongst HIV-infected patients who have advanced immunodeficiency. A range of other diagnostic tools are also at various stages of development., Summary: There is continued momentum and optimism regarding the developments in TB diagnostics. However, studies of clinical and programmatic impact and operational research are needed to guide implementation and scale-up of new assays in resource-limited settings. Further concerted efforts are needed to develop point-of-care assays which are desperately needed to accelerate progress in TB control.

Objective: The objective of this study was to define the test characteristics of plasma beta-glucan for diagnosis of Pneumocystis jirovecii pneumonia (PCP) in AIDS patients with respiratory symptoms., Design: Analysis of baseline blood samples in a randomized strategy study of patients with acute opportunistic infections, limited to participants with respiratory symptoms., Methods: Participants in the 282-person ACTG A5164 trial had baseline plasma samples assayed for beta-glucan testing. As part of A5164 trial, two study investigators independently adjudicated the diagnosis of PCP. Respiratory symptoms were identified by investigators from a list of all signs and symptoms with an onset or resolution in the 21 days prior to or 14 days following study entry. Beta-glucan was defined as positive if at least 80 pg/ml and negative if less than 80 pg/ml., Results: Of 252 study participants with a beta-glucan result, 159 had at least one respiratory symptom, 139 of whom had a diagnosis of PCP. The sensitivity of beta-glucan for PCP in participants with respiratory symptoms was 92.8% [95% confidence interval (CI) 87.2-96.5], and specificity 75.0% (95% CI 50.9-91.3). Among 134 individuals with positive beta-glucan and respiratory symptoms, 129 had PCP, for a positive predictive value of 96.3% (95% CI 91.5-98.8). Fifteen of 25 patients with a normal beta-glucan did not have PCP, for a negative predictive value of 60% (95% CI 38.7-78.9)., Conclusion: Elevated plasma beta-glucan has a high predictive value for diagnosis of PCP in AIDS patients with respiratory symptoms. We propose an algorithm for the use of beta-glucan as a diagnostic tool on the basis of the pretest probability of PCP in such patients.

Purpose of Review: The purpose of this study is to survey and synthesize recent progress in soluble biomarkers relevant to HIV-1 disease stages, progression and comorbidities., Recent Findings: Soluble biomarkers in plasma and other body fluids provide insight into many aspects of HIV-1 disease. Chemokines and defensins in breast milk and cervicovaginal secretions have been associated with HIV-1 susceptibility and transmission. Acute infection plasma cytokine storm components, including serum amyloid A, IFNγ-induced protein 10, interleukin (IL)-12, interferon-gamma (IFNγ), IL-7 and IL-15, may help predict viral load set-point and the subsequent disease progression. During chronic infection, IL-6, soluble (s)CD14, sCD163, high-sensitivity C-reactive protein, D-dimer, fibrin and hyaluronic acid can help predict comorbidities, and to some extent disease progression and mortality, in patients both on and off antiretroviral therapy. Furthermore, recent results suggest that assessment of combinations of soluble biomarkers may prove more powerful than the single factors alone in predicting disease., Summary: Soluble biomarkers help us understand HIV-1 immunopathogenesis. Integration of many biomarkers derived from a single plasma sample might become a powerful tool to optimize and individualize treatment and care.

Purpose of Review: HIV infection profoundly impairs the immune mechanisms needed to control and clear Leishmania infection, and outcomes in patients with HIV-associated visceral leishmaniasis are poor. This review summarizes recent work describing the epidemiology, presentation and outcomes of HIV-associated visceral leishmaniasis and discusses advances in diagnosis and management., Recent Findings: Studies have shown that serological tests can effectively diagnose HIV-associated visceral leishmaniasis, with a sensitivity of 98% if direct agglutination test and rK39 assays are used in combination. Few data exist to guide treatment recommendations. Observational data show high rates of toxicity and treatment failure with pentavalent antimonials, and their use is no longer recommended. Liposomal amphotericin B (L-AmB) is better tolerated, but outcomes are suboptimal, with mortality rates of 7-12%, and parasitological failure rates of up to 32%. Initial reports suggest that L-AmB and miltefosine in combination may be effective in HIV-associated visceral leishmaniasis; however, clinical trial data are lacking. Secondary prophylaxis reduces the rate of relapse, but optimal regimens have not been defined, and optimal timing of antiretroviral therapy initiation in patients with visceral leishmaniasis is unknown., Summary: Recent studies have demonstrated the inadequacy of current treatments for HIV-associated visceral leishmaniasis. Clinical trials are needed to improve early diagnosis, develop combination therapies and define effective secondary prophylaxis regimens.

Women account for half of the global human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) infections. Heterosexual contact is the leading risk factor in women. Over 50% of patients are significantly immunosuppressed at the time of diagnosis. Women with advanced HIV infection are at a risk for opportunistic infections (OIs). OIs lead to significant morbidity and cost. Some of OIs may impact women more significantly than men, that is, human papillomavirus infection and cervical cancer. OIs during pregnancy can increase the risk of maternal-to-child transmission of HIV and some OIs, such as Hepatitis C. This chapter will review of OIs that are most important in women's health.

Purpose of Review: In the present era of highly active antiretroviral therapy (HAART), the challenges that HIV/AIDS patients face with regard to ocular complications has changed immensely; nonetheless, significant ocular morbidity persists. We present an update on these challenges, focusing particularly on the relevant literature from the past 12-18 months., Recent Findings: Although its incidence has decreased substantially in the HAART era, cytomegalovirus (CMV) retinitis remains an important cause of ocular morbidity and predictor of mortality. Presently, patients with less than 50 CD4 T-cells/μL have an approximately equal risk of developing this potentially blinding ocular complication compared with the pre-HAART era. Less is understood about the current epidemiological considerations of ocular syphilis and HIV; however, patients with HIV may have increased likelihood of posterior syphilitic uveitis. Regarding the neuroretinal disorder associated with HIV, new ophthalmic imaging modalities are helping to uncover potentially associated structural alterations., Summary: Future challenges in the fight against HIV/AIDS-related eye disease will involve identifying additional factors conferring increased risk of CMV retinitis, understanding the scope of ocular syphilis and other eye infections in HIV patients, and furthering our understanding of the structural changes in neuroretinal disorder as an indicator of other end-organ damage.

Competing Interests: There are no conflicts of interest.

Purpose of Review: This review describes current epidemiology, diagnosis, treatment and prevention of adult HIV-related lung infections using evidence published within the past 2 years., Recent Findings: Recent evidence has helped better determine the importance of early initiation of antiretroviral therapy in co-infected individuals with advanced immune suppression. Although this has led to a greatly reduced incidence of opportunistic infections in people with HIV, Pneumocystis pneumonia remains common. Pneumonia due to bacterial pathogens, such as Streptococcus pneumoniae, also causes considerable disease burden, but emerging evidence of the clinical efficacy of pneumococcal vaccination, especially conjugated vaccines, offers considerable promise. As HIV-infected populations become older, more emphasis should be given to the potential benefit of influenza prevention, particularly with vaccination, and encouraging smoking cessation. Co-infection with tuberculosis is still a huge problem worldwide, but the recent development and use of simple clinical algorithms based on symptoms and point-of-care testing for recognizing active disease offers great potential., Summary: The lung remains an important site of disease in HIV-infected individuals. Increasing emphasis should be placed upon prevention of infection and modification of risk factors.

Purpose: To describe the transition to digital imaging and assess any impact on ocular disease classification., Methods: Film and digital images, acquired by certified photographers, were evaluated independently according to standard procedures for the following: image quality, presence of cytomegalovirus retinitis lesions, and their extent and proximity from disk and macula. Intergrader agreement within the digital medium was also assessed., Results: Among the 15 eyes with cytomegalovirus retinitis, the mean difference between film and digital images for linear distance of lesion edge to disk was 0.02 disk diameters, for distance to center of macula was -0.04 disk diameters, and area covered by cytomegalovirus retinitis was 0.95 disk area. There was no statistically significant difference in distance and area measurements between media. Intergrader agreement in measurements of digital images was excellent for distance and area estimated., Conclusion: Our results suggest that digital grading of cytomegalovirus retinitis in Longitudinal Studies of the Ocular Complications of AIDS is comparable with that from film regarding disease classification, measurements, and reproducibility. These findings provide support for continuity of grading data, despite the necessary transition in imaging media.

HIV-infected patients may develop rare anogenital pseudotumoral herpes potentially mimicking epidermoid carcinoma. We assessed treatment in five new cases with a median follow-up of 3.3 years. Recurrence and clinical nucleoside analog resistance were observed in all patients. All drug treatments were only temporarily curative and clinical responses varied between patients and recurrences. Foscavir seemed to be the most appropriate second-line treatment and cidofovir or thalidomide should be considered as alternative treatments.

Mycobacterium genavense, a nontuberculous mycobacterium, led to devastating infections in patients with acquired immunodeficiency syndrome (AIDS) before highly active antiretroviral therapy (HAART) was available, as well as in other immunocompromised patients. We conducted the current study to describe the features of this infection in patients infected with human immunodeficiency virus (HIV) in the HAART era and in non HIV-infected patients.We conducted a retrospective cohort survey in France. All patients with M. genavense infection diagnosed from 1996 to 2007 at the National Reference Center, Institut Pasteur, Paris, were identified and their clinical, laboratory, and microbiologic data were centralized in a single database. Twenty-five cases of M. genavense infection originating from 19 centers were identified. Twenty patients had AIDS, 3 had solid organ transplantation, and 2 had sarcoidosis. Sixty-four percent (n = 16) were male, mean age was 42 years, and median CD4 count was 13/mm (range, 0-148/mm) in patients with AIDS. Twenty-four patients had disseminated infection with fever (75%, n = 18), weight loss (79%, n = 19), abdominal pain (71%, n = 17), diarrhea (62.5%, n = 15), splenomegaly (71%, n = 17), hepatomegaly (62.5%, n = 15), or abdominal adenopathy (62.5%, n = 15). M. genavense was isolated from the lymph node (n = 13), intestinal biopsy (n = 9), blood (n = 6), sputum (n = 3), stool (n = 3), and bone marrow (n = 5). Eleven patients (44%) died, 8 (32%) were considered cured with no residual symptoms, and 6 (24%) had chronic symptoms. The 1-year survival rate was 72%.The prognosis of M. genavense infection in HIV-infected patients has dramatically improved with HAART. Clinical presentations in HIV and non-HIV immunocompromised patients were similar.

WHO policy states that tuberculosis (TB) should be diagnosed and treated before starting antiretroviral treatment (ART). However, during the pre-ART screening period, diagnosing or excluding TB can be a lengthy process and may cause undesirable delays in ART initiation. In this observational study from South Africa, we report that initiation of ART before TB treatment in patients with delayed diagnoses of culture-positive prevalent TB was not associated with adverse clinical, immunological or virological outcomes during 12-month follow-up.

The aim of our study was to determine the usefulness of pneumococcal urinary antigen (UA) collected in the emergency department (ED) for the microbiologic diagnosis of community-acquired pneumonia (CAP) in HIV patients and to compare it with other diagnostic tests. Prospective study from 1 January 2007 to 31 December 2008 included HIV-infected patients admitted at the ED with respiratory symptoms and who were diagnosed of CAP. UA, two blood cultures and sputum sample for culture determination were collected from every patient. Sixty-four patients were included. The mean age was 42 years. A total of 31 (48%) UA tests, 12 (19%) blood cultures and 21 (33%) sputum cultures tested positive. A microbiological diagnosis was obtained in 38 (59%) cases. Pneumococcal pneumonia was diagnosed in 32 cases. The statistical analysis showed that the test with best performance was the UA, both in relation to blood and sputum cultures (P<0.05). Two patients died during hospitalization (series mortality of 3%). In conclusion, given its good diagnostic performance, UA should be requested in the ED for the aetiological diagnosis of CAP.

Despite the advent of new antifungal agents, coccidioidal meningitis (CM) remains a difficult-to-treat condition with significant morbidity and mortality. In this study we directly compare the clinical presentation and management of patients with Coccidioides immitis meningitis in the azole era (after 1980) to that of a cohort of patients from the pre-azole era. We reviewed 30 CM cases seen at 3 Los Angeles hospitals between the years 1993 to 2008 ("2008 cohort") and compared them to 31 patients ("1980 cohort") described by Bouza et al in a previous study. The demographics and clinical presentation of patients in the 2008 cohort were similar to those of the 1980 cohort except for a higher incidence of Hispanic patients (2008: 53% vs. 1980: 6%) and a greater percentage of patients with underlying, predisposing clinical conditions (2008: 66% vs. 1980: 32%). Ten patients in the 2008 cohort had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), a condition not reported in the earlier study. Laboratory findings were similar between the 2 groups except for a lower incidence of peripheral leukocytosis and eosinophilia in the 2008 group.There were marked differences in drug treatment between the 2 eras. In the 2008 cohort, 29 patients received fluconazole therapy: 13 were treated with fluconazole monotherapy, and 16 received a combination of fluconazole and intravenous amphotericin B. Although almost all patients (29/31) in the 1980 cohort received intrathecal amphotericin B, only 3 patients in the 2008 study received amphotericin B via this route. With respect to complications of CM, a similar percentage of patients in each cohort developed complications such as stroke and hydrocephalus. The 2008 cohort (40%) had similar mortality compared to patients in the 1980 study (39%); survivors in both groups experienced significant impairment of activities of daily living. Although recommended as first-line therapy for CM, azole-based therapies are not curative and do not necessarily prevent complications associated with the disease.CM remains a serious illness with a high rate of morbidity and mortality. Immunocompromised individuals, especially those with HIV/AIDS, are at special risk for CM and represent a greater share of the overall population with this condition. Despite the clear advantages of azole treatment in CM, new therapeutic approaches are needed to provide definitive cure and to reduce the need for long-term suppressive therapy.

Purpose: The purpose of this study was to use spectral domain-optical coherence tomography in imaging retina and vitreoretinal relationship in healed cytomegalovirus (CMV) retinitis., Methods: Patients with a history of confirmed CMV retinitis and a healed CMV scar on clinical examination underwent spectral domain-optical coherence tomography examinations using a Spectralis Heidelberg retinal angiograph/optical coherence tomography instrument (Heidelberg Engineering, Heidelberg, Germany). Horizontal and vertical cross-sectional B-scans 6 mm x 6 mm passing through the center and margins of healed CMV scars and adjacent retina were obtained. We analyzed the integrity of retinal layers in the area of the CMV scar, integrity of retinal layers at the margins of the CMV scar, margins of the scar and adjacent nonaffected retina, and any structural alterations in the retina or vitreous., Results: Eleven eyes (50%) had vitreous detached, and 11 eyes attached over the area of healed retinitis. Nineteen eyes (86%) had an epiretinal membrane, and 12 eyes (54%) had vitreoretinal gliosis present over the healed retinitis or in its vicinity. The epiretinal membrane and vitreoretinal gliosis occurred concomitantly in 10 eyes and could be well differentiated on scans. None of these were found in control eyes., Conclusion: This first in vivo study of vitreoretinal interface in inactive CMV retinitis shows that the vitreoretinal interface in healed CMV is pathologically changed. The presence of epiretinal membranes, vitreoretinal gliosis, and traction may help explain the higher incidence of retinal elevation, retinal breaks, and retinal detachment in these eyes.

Background: Annual syphilis testing was reintroduced in the Swiss HIV Cohort Study (SHCS) in 2004. We prospectively studied occurrence, risk factors, clinical manifestations, diagnostic approaches and treatment of syphilis., Methods: Over a period of 33 months, participants with positive test results for Treponema pallidum hemagglutination assay were studied using the SHCS database and an additional structured case report form., Results: Of 7244 cohort participants, 909 (12.5%) had positive syphilis serology. Among these, 633 had previously been treated and had no current signs or symptoms of syphilis at time of testing. Of 218 patients with newly detected untreated syphilis, 20% reported genitooral contacts as only risk behavior and 60% were asymptomatic. Newly detected syphilis was more frequent among men who have sex with men (MSM) [adjusted odds ratio (OR) 2.8, P < 0.001], in persons reporting casual sexual partners (adjusted OR 2.8, P < 0.001) and in MSM of younger age (P = 0.05). Only 35% of recommended cerebrospinal fluid (CFS) examinations were performed. Neurosyphilis was diagnosed in four neurologically asymptomatic patients; all of them had a Venereal Disease Research Laboratory (VDRL) titer of 1:>or=32. Ninety-one percent of the patients responded to treatment with at least a four-fold decline in VDRL titer., Conclusion: Syphilis remains an important coinfection in the SHCS justifying reintroduction of routine screening. Genitooral contact is a significant way of transmission and young MSM are at high risk for syphilis. Current guidelines to rule out neurosyphilis by CSF analysis are inconsistently followed in clinical practice. Serologic treatment response is above 90% in the era of combination antiretroviral therapy.

Objective: To determine the baseline prevalence of tuberculosis (TB) in a cohort using a strategy of intensive pretreatment screening for TB and the subsequent incidence rate and temporal distribution of cases during the first year of antiretroviral therapy (ART)., Design: Prospective observational community-based ART cohort in South Africa., Methods: Adults enrolling for ART and who did not have a current TB diagnosis were intensively screened for TB at baseline using culture of two sputum samples, chest radiography and investigations for extrapulmonary disease as required. Patients who developed symptoms consistent with incident TB during ART were similarly investigated., Results: Two hundred forty-one patients had a median CD4 cell count of 125 cells/microl (interquartile range 70-186) and 200 (83%) started ART. TB was diagnosed in 87 (36%) patients, with 82% of pulmonary cases being culture-proven. Most TB cases (87%) were prevalent disease detectable at baseline, whereas just 11 (13%) were incident cases that presented during the first year of ART. The incidence rate during 0-4 months of ART was similar to the rate during months 5-12 of ART [10.9 (95% confidence interval [CI] 4.6-23.3) cases per 100 person-years versus 8.1 (95% CI 3.6-18.0) cases per 100 person-years]., Conclusion: Systematic culture-based screening detected a very high burden of prevalent TB present at baseline. This intensified screening strategy was associated with an approximately two-fold lower incidence rate in the first 4 months of ART than previously observed in this cohort. This suggests that many incident cases of symptomatic TB presenting during early ART can be detected as prevalent disease prior to ART initiation using sensitive diagnostic tests.

Purpose of Review: Drug-resistant tuberculosis (TB) is of increasing global concern. One of the hardest hit regions is southern Africa. This study focuses on a concise update on recently published developments in the field., Recent Findings: There is mounting evidence from high-coprevalence areas that the TB and HIV pandemics must be viewed as an entity and tackled together. In that context, it has become clear that a shift may be required from standard hospital-based models of care towards community-based approaches. Innovative rapid diagnostics to detect TB drug resistance suitable for the use in resource-poor settings and novel drugs effective against drug-resistant Mycobacterium tuberculosis strains are currently developed., Summary: In order to allow for a maximum impact of novel interventions on the problem of multidrug-resistant and extensively drug-resistant TB, public health systems and existing TB programs must be strengthened significantly.

Objective: To estimate rates of recurrent tuberculosis due to reinfection and relapse, by HIV status, in a general population., Design: Long-term cohort study in Karonga district, rural Malawi., Methods: All tuberculosis patients with culture-proven disease in Karonga district were followed up after treatment. HIV testing was offered and all Mycobacterium tuberculosis isolates were fingerprinted using IS6110 RFLP. Fingerprints from initial and recurrent disease episodes were compared to distinguish relapse and reinfection: a second episode was considered a relapse if the fingerprint was identical or differed by only 1-4 bands and was the first occurrence of that pattern in the population. Rates of and risk factors for recurrence, reinfection disease, and relapse were estimated using survival analysis and Poisson regression., Results: Five hundred and eighty-four culture-positive episodes of tuberculosis were diagnosed and treatment was completed during 1995-2003 in patients with known HIV status; 53 culture-positive recurrences occurred by May 2005. Paired fingerprints were available for 39 of these. Reinfections accounted for 1/16 recurrences in HIV-negative and 12/23 in HIV-positive individuals. Rates of relapse were similar in HIV-positive and HIV-negative individuals. Using multiple imputation to allow for missing fingerprint information, the rate of reinfection disease in HIV-positive individuals was 2.2/100 person-years, and in HIV-negative individuals 0.4/100 person-years., Conclusions: HIV increases the rate of recurrent tuberculosis in this setting by increasing the rate of reinfection disease, not relapse.

Interferon gamma (IFNgamma)-based in-vitro assays have suboptimal sensitivity, especially in immunocompromised individuals, which emphasizes the need for alternative markers for tuberculosis (TB) diagnosis. We compared TB antigens-specific IFNgamma and IFNgamma-inducible protein-10 levels in culture of whole blood samples from HIV-TB patients. We report that IFNgamma-inducible protein-10 detects a greater number of HIV-TB cases than IFNgamma and suggest that IFNgamma-inducible protein-10 may be a better alternative marker for latent TB infection diagnosis among immunocompromised individuals.

Background: The International Network for the Study of HIV-associated IRIS (INSHI) recently published criteria for tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) diagnosis. The performance of this definition and clinical manifestations of TB-IRIS were studied., Methods: Antiretroviral therapy-naive HIV/TB Thai patients receiving antituberculous therapy were enrolled during 2006-2007 and prospectively followed through 24 weeks of antiretroviral therapy. Patients were defined as having paradoxical TB-IRIS if they fulfilled the 'study definition' by French 2004 and were confirmed by an external reviewer. All were later compared by the classification according to 'INSHI-2008'., Results: For the 126 patients, median baseline CD4 cell count was 43 cells/microl and HIV-1 RNA was 5.9 log(10) Y copies/ml. Seventy-three (58%) had extrapulmonary/disseminated TB. Twenty-two (18%) and 21 (17%) fulfilled TB-IRIS criteria according to the study definition and INSHI-2008 definition, respectively. Two (2%) were diagnosed by study definition only and one (1%) by INSHI-2008 definition only. Twenty (16%) were concordantly diagnosed by both definitions and 103 (82%) were consistently negative. Eighteen (82%) had worsening of a preexisting site, whereas four (18%) had TB-IRIS in a new location. Lymph node enlargement (73%) and fever (59%) were common in TB-IRIS. Sensitivity and specificity of INSHI-2008 was 91% (95% confidence interval, 72-98%) and 99% (95% confidence interval, 95-99.8%), respectively. Positive predictive value was 95% and negative predictive value was 98%. By multivariate analysis, factors predicting TB-IRIS were extrapulmonary TB (odds ratio, 8.63) and disseminated TB (odds ratio, 4.17)., Conclusion: There was high concordance between the INSHI-2008 and French 2004 definition for TB-IRIS diagnosis in HIV/TB patients with relatively high rate of paradoxical TB-IRIS. This suggests that lack of HIV-1 RNA and CD4 cell count monitoring does not impede the ability to diagnose TB-IRIS.

Pneumocystis pneumonia and AIDS have been linked together for many years. In the 1980s and 1990s, these diseases often resulted in admission to the critical care unit for many patients. Since the discovery of antiretroviral therapy and Pneumocystis prophylaxis, this has been a less frequent occurrence. Knowledge about caring for this patient in the critical care unit is often not available. Psychological and physiological needs common to this population are different from other populations and must be addressed. Pharmacological challenges are common and may go unrecognized until complications ensue. This article seeks to alleviate some of the mystery associated with these issues.

Purpose of Review: In this review, we focus on the clinical features, diagnosis and management of pneumococcal pneumonia in HIV-infected and noninfected patients, with particular attention to the most recent advances in this area., Recent Findings: Classical clinical features are found in young adults, whereas atypical forms occur in immunocompromised patients including HIV-infected individuals. Bacteremic pneumococcal pneumonia is more frequently observed in HIV-infected and also in low-risk patients, according to the Pneumonia Severity Index (PSI). Pneumococcal pneumonia diagnostic process includes physical examination, radiologic findings and microbiologic diagnosis. However, etiologic diagnosis using traditional culture methods is difficult to obtain. In this setting, urinary antigen test, which recognizes Streptococcus pneumoniae cell wall C-polysaccharide, increases the probability of etiologic diagnosis. A correct management approach is crucial in reducing pneumococcal pneumonia mortality. The use of the PSI helps clinicians in deciding between inpatient and outpatient management in immunocompetent individuals, according to Infectious Diseases Society of America (IDSA)-American Thoracic Society (ATS) guidelines. Recent findings support PSI utility also in HIV-infected patients. Recently, efficacy of pneumococcal vaccine in reducing pneumococcal disease incidence has been evidenced in both HIV-infected and noninfected individuals., Summary: Rapid diagnosis and correct management together with implementation of preventive measures are crucial in order to reduce pneumococcal pneumonia related incidence and mortality in HIV-infected and noninfected patients.

Objective: The purpose was to characterize the spectrum of imaging findings of nontuberculous mycobacterial immune reconstitution syndrome in patients infected with the human immunodeficiency virus., Methods: A retrospective review of 33 human immunodeficiency virus-infected patients with nontuberculous mycobacterial immune reconstitution syndrome was performed. Radiography, ultrasound, and computed tomography (CT) imaging was reviewed., Results: Intrathoracic and intra-abdominal abnormalities were identified in 16 and 14 patients, respectively. Lymphadenopathy was detected on chest radiographs in 11 patients and on CT in 13. Focal consolidation (n = 8) and centrilobular nodularity (n = 8) were common CT findings. Lymphadenopathy was the predominant abdominal finding (n = 10). Splenomegaly (n = 9), ascites (n = 7), and multiple hypoattenuating splenic lesions (n = 6) were additional findings. Peripheral lymph node masses were detected in 7 patients., Conclusions: The most common manifestation of nontuberculous mycobacterial immune reconstitution syndrome is lymphadenopathy. Other common findings are pulmonary consolidation and centrilobular nodularity, ascites, splenomegaly, multiple hypoattenuating splenic lesions, and peripheral lymphadenopathy.

Staphylococcus aureus is the leading cause of infectious endocarditis and its mortality has remained high despite better diagnostic and therapeutic procedures over time. We conducted a retrospective review of 133 cases of definite S. aureus endocarditis seen at a single tertiary care hospital over 22 years to assess changes in the epidemiology and incidence of the infection, manifestations, outcome, risk factors for mortality, and impact of cardiac surgery on prognosis.Patients were classified into 2 groups: 1) right-sided endocarditis (64 patients) and 2) left-sided endocarditis (69 patients). While the number of cases of left-sided endocarditis remained steady at 1-3 cases per 10,000 admissions, the incidence of right-sided endocarditis, after a peak in the early 1990s, declined to almost disappear in 2001. Among the cases of right-sided endocarditis, we found 2 subsets of patients with different clinical features and prognosis: the first subset comprised 53 intravenous drug abusers, and the second subset comprised 11 patients with catheter-associated S. aureus bacteremia and endocarditis. Fifty-one patients were human immunodeficiency virus (HIV)-positive drug abusers, most of whom (80.3%) had right-sided endocarditis. We did not find differences in mortality between HIV-positive and HIV-negative individuals; mortality seemed to depend more on the site of the heart involved than on HIV status.Among the cases of left-sided endocarditis, the mitral valve was more commonly involved than the aortic valve (61% vs. 30%). Overall, 74% of patients with left-sided endocarditis developed 1 or more cardiac or extracardiac complication. In comparison, only 23.4% of patients with right-sided endocarditis developed complications.Prosthetic valve endocarditis (PVE) was hospital-acquired more frequently than native valve endocarditis (NVE). Patients with PVE had a shorter duration of symptoms until diagnosis and presented with or developed cardiac murmurs less frequently than patients with NVE. Cardiac failure (49%), renal failure (43%) and central nervous system (CNS) events (35%) were frequently observed in patients with both PVE and NVE. Valve replacement was more frequently needed and more rapidly performed in patients with PVE than in their counterparts with NVE.The overall mortality of patients with right-sided endocarditis was 17%. While the mortality of right-sided endocarditis in injection drug users was 3.7%, the mortality of patients with right-sided endocarditis associated with infected intravenous catheters was 82% (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.001-0.07). For left-sided endocarditis mortality was 38% and was not significantly different in patients with NVE or PVE (OR, 0.65; 95% CI, 0.23-1.87). CNS complications were associated with mortality in both NVE (OR, 6.55; 95% CI, 1.78-24.04) and PVE (OR, 32; 95% CI, 2.63-465.40). Development of 2 or 3 complications was associated with an increased risk of mortality (OR, 5.59; 95% CI, 1.08-28.80 and OR, 9.25; 95% CI, 1.36-62.72 for 2 vs. 1 complication and for 3 vs. 2 complications, respectively).Surgical treatment did not significantly influence mortality in cases of NVE, (OR, 3.19; 95% CI, 0.76-13.38) but significantly improved the prognosis of patients with PVE (OR, 69; 95% CI, 2.89-1647.18).S. aureus endocarditis is an aggressive, often fatal, infection. The results of the current study suggest that valve replacement will improve the outcome of infection, particularly in patients with PVE.

Tuberculosis (TB) and coccidioidomycosis can have similar clinical and radiologic presentations but require different treatments. Coinfection with TB and Coccidioides immitis is uncommonly reported and may be underdiagnosed in endemic areas.We performed a retrospective review of the medical records of all patients admitted to a TB referral hospital between 1995 and 2007, and selected all cases of TB and coccidioidomycosis coinfection in patients aged 18 years or older. All admitted patients had a diagnosis of TB and had sputum cultures for both pathogens. We reviewed clinical, laboratory, and radiologic features of the cases, and noted antimicrobial treatments received and outcomes.We identified 9 patients, of whom 7 (78%) were Hispanic. Most patients were male (8/9, 89%), and all were diagnosed with coccidioidomycosis after TB. Three (33%) patients had drug-resistant TB. Six patients had culture-positive TB at the time of the double diagnosis, and 2 patients developed active coccidioidomycosis during their hospital stay. Only 1 had human immunodeficiency virus/acquired immunodeficiency syndrome (HIV-AIDS) (CD4 count, 20 cells/mm). All but 2 patients were treated with antifungal agents. Two patients died, 1 of whom had AIDS. Radiologic studies were unable to distinguish between TB and coccidioidomycosis, except for a patient who developed a new air-fluid level in a previously stable cavity.TB and coccidioidomycosis coinfection should be suspected in coccidioidomycosis-endemic regions among patients with TB who fail to improve clinically or radiologically despite adequate, culture-directed therapy.

Objective: To evaluate the interferon-gamma-releasing assays QuantiFERON-tuberculosis (TB) Gold and T-SPOT.TB in addition to tuberculin skin test (TST) for diagnosis of latent tuberculosis infection in HIV patients., Design, Setting and Participants: Prospective cross-sectional study for asymptomatic HIV-infected outpatients from a large University hospital., Intervention: Simultaneous performance of QuantiFERON-TB Gold, T-SPOT.TB and TST., Main Outcome Measures: Incidence and risk factors for a positive test reaction and the concordance (kappa) between the tests were investigated., Results: Of 286 enrolled patients, 81% were men; median age was 44 years, the median CD4 cell count 408/microl (range 7-1510) with a median nadir of 126/microl (range 0-749). A number of patients (63.8%) had undetectable HIV RNA (<50 copies/ml). Both T-SPOT.TB and QuantiFERON-TB showed more positive test results than TST: 25.2 and 20.0% (P = 0.133) compared with 12.8% (P < 0.001 and P = 0.008, respectively). Agreement between T-SPOT.TB and TST (kappa = 0.201) respectively QuantiFERON-TB and TST (kappa = 0.335) was fair, but only poor between the serological assays (kappa = 0.146). T-SPOT.TB provided more indeterminate results than QuantiFERON-TB (8 vs. 1/256, P < 0.01). Patients with a positive QuantiFERON-TB result had higher median CD4 cell counts (457 vs. 405 cells/microl for patients with negative result, P = 0.044); the amount of released interferon-gamma correlated with CD4 cell counts (rho = 0.199; P < 0.002). T-SPOT.TB results were independent from CD4 cell counts., Conclusion: In HIV-infected patients from a low prevalence TB country, both interferon-gamma assays are more sensitive than TST, but seem to be less sensitive than in immunocompetent patients. The blood tests show poor agreement and differ in their dependence on the CD4 cell count.