Incidence and predictors of reoccurrence of opportunistic infection among adult HIV/AIDS patients attending ART clinic at public health facilities in Arba Minch town, southern Ethiopia: A retrospective cohort study.

BACKGROUND: Human immunodeficiency virus (HIV) infected individuals are prone to opportunistic infections (OIs) due to HIV mediated immune suppression. When opportunistic infections occur in the form of relapse or reinfection, it is said to be reoccurrence. This study was aimed to assess Incidence and predictors of reoccurrence of opportunistic infections among adult people living with HIV (PLHIV) attending ART clinics in Arba Minch Town, Southern Ethiopia. METHODS: This retrospective cohort study was conducted on 450 HIV/AIDS patients attending anti-retro viral therapy (ART) clinics in Arba Minch town, southern Ethiopia. Simple random sampling technique was used. Kaplan-Meier graph and log rank test were used for group wise comparison. Bivariate and multivariable Cox Proportional Hazard Regression model were used to identify independent predictors of reoccurrence of opportunistic infection. RESULT: One hundred nineteen HIV/AIDS patient had reoccurrence of opportunistic infection. The incidence rate was 11.5 per 1000 person months. The mean time of reoccurrence was 56 months. One of the most reoccurred OIs was pulmonary tuberculosis (PTB). Predictors that were associated significantly were recent cell differentiation 4 (CD4) count, recent body mass index (BMI), recent functional status, and duration on anti-retroviral therapy (ART). CONCLUSION: Though the incidence rate of OIs decreased from previous findings, attention should be given to HIV patients with low CD4 count, low BMI and for those bedridden patients.

Pneumocystis pneumonia, a COVID-19 mimic, reminds us of the importance of HIV testing in COVID-19.

While clinical environments are highly focused on COVID-19, reports of missed or delayed treatment for conditions that imitate COVID-19, such as pneumonia caused by the fungus Pneumocystis jirovecii, are emerging. Given the uncertain spectrum of COVID-19 presentations and variable sensitivity of laboratory tests for SARS-CoV-2, there is a risk that, without a high index of suspicion, alternative aetiologies may be overlooked while pursuing a diagnosis of COVID-19. The British HIV Association has been calling for the inclusion of HIV testing in all patients admitted to hospital with suspected COVID-19. In this article we reflect on the importance of including HIV testing to prevent avoidable morbidity and mortality in our patients.

A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections: Study protocol for the optimal early intervention for cryptococcal antigenemia in HIV-infected patients.

BACKGROUND: Asymptomatic cryptococcal antigenemia is a state of cryptococcal infection commonly seen in immunocompromised HIV-infected persons. Without early intervention, a proportion of HIV-infected persons with cryptococcal antigenemia may go on to develop cryptococcosis, especially cryptococcal meningitis, which is associated with high mortality. The benefits of antifungal intervention and optimal therapeutic intervention regimens for HIV-infected persons with cryptococcal antigenemia remain controversial. We therefore designed the present study in order to investigate the necessity of, and the optimal regimens for antifungal intervention in the clinical management of cryptococcal antigenemia in HIV-infected populations. METHODS/DESIGN: This study will be an open-labeled, multi-center, prospective, randomized controlled trial, and 450 eligible participants will be randomized into a control arm and 2 intervention arms at a 1:1:1 ratio, with 150 subjects in each arm. Participants in the control arm will not receive antifungal treatment during the study period. Participants in intervention arm 1 will receive oral fluconazole 800 mg/day for 2 weeks, followed by 400 mg/day for 8 weeks and 200 mg/day for 42 weeks, and participants in intervention arm 2 will receive oral fluconazole 400 mg/day for 52 weeks. The primary outcome is the incidence of CM among the 3 groups during the study period. The secondary outcomes include the differences in all-cause mortality, proportion of patients reverting to blood CrAg negativity, change of CrAg titers, and adverse events among the 3 groups during the follow-up period. DISCUSSION: We envisage that the results of this study will reveal the necessity of, and the optimal therapeutic regimens for, antifungal intervention in clinical management of HIV-infected patients with cryptococcal antigenemia. TRIAL REGISTRATION: The study was registered as one of the 12 clinical trials under a general project at the Chinese Clinical Trial Registry on February 1, 2019, and the registration number of the general project is ChiCTR1900021195.

A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections: Study protocol for antiretroviral therapy timing in AIDS patients with toxoplasma encephalitis.

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.

Resurgence of ocular syphilis in British Columbia between 2013-2016: a retrospective chart review.

OBJECTIVE: To characterize the trends and explore the demographics, ophthalmic manifestations, and outcomes of ocular syphilis cases in British Columbia. DESIGN: Retrospective chart review. PARTICIPANTS: Ocular syphilis cases reported to the British Columbia Centre for Disease Control (BCCDC) between January 2013 and December 2016. METHODS: The demographic and clinical data were extracted from the BCCDC's centralized sexually transmitted infection database and the ophthalmologists' clinical charts. RESULTS: There was a steady increase in the rate of syphilis infection per 100 000 population, from 3.4 in 2010 to 18.4 in 2018. There were 39 ocular syphilis cases identified from January 2013 to December 2016. The median age was 50 years (interquartile range: 40-59.5 years); 82.1% were male and 51.3% were HIV positive. The clinical charts belonging to 32 patients were available for review, 14 of which (43.8%) presented with bilateral ocular complaints (46 affected eyes). The most commonly noted ocular presentations were uveitis (93.5%), including retinal vasculitis in 54.3%, and optic nerve involvement in 65.2% (which included papillitis, optic nerve swelling, or pallor). Panuveitis was the most frequent type of uveitis (52.2% of all eyes); 77.8% of affected eyes with best-corrected visual acuity (BCVA) ≤20/50 on presentation had an improvement of 2 or more Snellen lines of visual acuity at their final assessment. At presentation, 37.0% of eyes had BCVA ≤20/200, which decreased to 17.1% at final assessment. CONCLUSION: Ocular syphilis, although rare, is on the rise globally and can result in serious ocular sequelae. A high index of suspicion is required for proper diagnosis and treatment.

Epidemiological, clinical and biological profile of neuromeningeal cryptococcosis among people living with HIV in Kinshasa, Democratic Republic of Congo.

Neuromeningeal cryptococcosis (NMC) is one of the most frequent opportunistic infections (OI) in Human Immunodeficiency Virus (HIV) infection. In Kinshasa, the latest data on cryptococcosis were published in 1996. The objective was to describe the epidemiological, clinical and biological profiles of NMC in HIV-infected people living in Kinshasa. This is a descriptive study based on the medical records of patients who attended three clinics in Kinshasa between January 1 s t 2011 and December 31st 2014. Only the medical records of HIV-infected people presenting the NMC were reviewed. During the 4 year-period of the study, 261 HIV-positive patients presented to the clinics for neuromeningeal syndrome, including 23 with NMC. The global prevalence of NMC was 8.8% for the three clinics. The mean age was 42.8 ± 9.5 years, with male predominance (65.2%). The main symptoms were headache (73.9%), neck stiffness (60.9%), fever (47.8%), and coma (47.8%). Biological records were as follows: median CD4 cell count was 79 cells/mm3; cerebrospinal fluid (CSF) was clear for 56.5% of the cases with predominance of neutrophils in 73.9%. The outcome was fatal in 34.8% of cases. The prevalence and therapeutic outcome of NMC show that it constitutes a non-negligible OI in Kinshasa, especially in HIV-infected people at the AIDS stage. As HIV-infected people with severe immunosuppression are the most affected by NMC, active preventive measures should benefit this vulnerable category of people.

Dyspnea in homosexual male patients: throwback to an occasionally forgotten but severe clinical presentation of HIV/AIDS.

Pneumocystis jirovecii pneumonia (PJP) can be a severe indicator disease of acquired immunodeficiency syndrome (AIDS). We present two cases of homosexual male patients who came to the emergency unit of a Belgian hospital because of shortness of breath. Both men had been sent back home, initially diagnosed with a benign viral infection. Because of worsening symptoms and gradually evolving hypoxemia, both patients came back and were admitted to the hospital with a diagnosis of (microbiology proven) Pneumocystis jirovecii pneumonia. HIV serology in both men was tested and was clearly positive, indicating a new diagnosis of HIV infection. In this article, we provide an overview of this possibly severe AIDS defining condition. First, we give an introduction of the history of HIV/AIDS and its occurrence in homosexual males in Europe. Secondly, we provide an overview of the diagnosis and treatment of Pneumocystis jirovecii pneumonia. Finally, since the first case reports of Pneumocystis jirovecii pneumonia at the beginning of the AIDS epidemic also included homosexual men, we emphasize the potential importance of a sexual anamnesis in young male patients with an initial complaint of dyspnea.

Cognitive Impairment in Zambians With HIV Infection and Pulmonary Tuberculosis.

BACKGROUND: HIV infection may result in neurocognitive deficits, but the effects of pulmonary tuberculosis (TB+), a common comorbid condition in HIV infection, on cognition in HIV infections are unknown. Accordingly, we examined the effects of TB+, on neurocognitive functioning in HIV-infected (HIV+) Zambian adults. SETTING: All participants were drawn from HIV clinics in and around Lusaka, the capital of Zambia. METHODS: Participants were 275 HIV+, of whom 237 were HIV+ and TB-negative (HIV+/TB-), and 38 also had pulmonary TB+ (HIV+/TB+). Controls were 324 HIV- and TB-uninfected (HIV-) healthy controls. All HIV+ participants were prescribed combination antiretroviral treatment (cART). Published, demographically corrected Zambian neuropsychological norms were used to correct for effects of age, education, sex, and urban/rural residence. RESULTS: Neuropsychological deficits, assessed by global deficit scores, were more prevalent in this order: 14% (46 of 324) of HIV- controls, 34% (80 of 237) of HIV+/TB-, and 55% (21 of 38) of HIV+/TB+ group. Thus, both HIV-infected groups evidenced more impairment than HIV- controls, and the HIV+/TB+ group had a higher rate of neurocognitive impairment than the HIV+/TB- group. HIV+/TB+ patients were more likely to be male, younger, less-educated, and have lower CD4 counts and detectable HIV RNA in blood compared with the HIV+/TB- patients. CONCLUSIONS: In HIV infection, TB may contribute to cognitive impairment, even after controlling for lower CD4 counts and viral load. Thus, systemic inflammation from HIV and TB and more advanced immune deficiency at diagnosis of HIV may contribute to impaired cognition in HIV+/TB+ patients.

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). METHODS: In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. RESULTS: Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. CONCLUSION: High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB.

Updating vital status by tracking in the community among patients with epidemic Kaposi sarcoma who are lost to follow-up in sub-Saharan Africa.

BACKGROUND: Throughout most of sub-Saharan Africa (and, indeed, most resource-limited areas), lack of death registries prohibits linkage of cancer diagnoses and precludes the most expeditious approach to determining cancer survival. Instead, estimation of cancer survival often uses clinical records, which have some mortality data but are replete with patients who are lost to follow-up (LTFU), some of which may be caused by undocumented death. The end result is that accurate estimation of cancer survival is rarely performed. A prominent example of a common cancer in Africa for which survival data are needed but for which frequent LTFU has precluded accurate estimation is Kaposi sarcoma (KS). METHODS: Using electronic records, we identified all newly diagnosed KS among HIV-infected adults at 33 primary care clinics in Kenya, Uganda, Nigeria, and Malawi from 2009 to 2012. We determined those patients who were apparently LTFU, defined as absent from clinic for ≥90 days at database closure and unknown to be dead or transferred. Using standardized protocols which included manual chart review, telephone calls, and physical tracking in the community, we attempted to update vital status amongst patients who were LTFU. RESULTS: We identified 1222 patients with KS, of whom 440 were LTFU according to electronic records. Manual chart review revealed that 18 (4.1%) were classified as LFTU due to clerical error, leaving 422 as truly LTFU. Of these 422, we updated vital status in 78%; manual chart review was responsible for updating in 5.7%, telephone calls in 26%, and physical tracking in 46%. Among 378 patients who consented at clinic enrollment to be tracked if they became LTFU and who had sufficient geographic contact/locator information, we updated vital status in 88%. Duration of LTFU was not associated with success of tracking, but tracking success was better in Kenya than the other sites. CONCLUSION: It is feasible to update vital status in a large fraction of patients with HIV-associated KS in sub-Saharan Africa who have become LTFU from clinical care. This finding likely applies to other cancers as well. Updating vital status amongst lost patients paves the way towards accurate determination of cancer survival.

Rare presentation of intractable tuberculous panophthalmitis with intraocular and intraorbital abscesses: a case report.

BACKGROUND: We report a rare presentation of extrapulmonary tuberculosis. CASE PRESENTATION: A 29-year-old Burmese woman with human immunodeficiency virus infection and known pulmonary tuberculosis who had been treated for 5 months presented to our hospital with unilateral progressive painful visual loss of 1 month's duration. She was diagnosed with tuberculous panophthalmitis with subretinal and intraorbital abscesses, conjunctival abscess, and extraocular muscle tuberculoma. The diagnosis was confirmed by a conjunctival pus swab with a positive result for acid-fast bacilli and a positive result for a mycobacterial culture. There was high suspicion of multidrug-resistant tuberculosis. Despite receiving ongoing aggressive treatment with conventional antituberculous medications, this patient required subtotal orbital exenteration to control her infection and prevent further progression. Second-line antituberculous medications were added to the first-line therapy, with satisfactory results achieved. CONCLUSIONS: Tuberculous panophthalmitis with intraocular and intraorbital abscesses is a rare presentation of extrapulmonary tuberculosis. Patients who do not respond to first-line antituberculous therapy might be infected with either single-drug or multidrug-resistant Mycobacterium tuberculosis. Patient compliance is one of the key factors that can alter the course of treatment. Careful patient monitoring can improve disease progression, outcome, and prognosis.

Pulmonary TB: varying radiological presentations in individuals with HIV in Soweto, South Africa.

Background: HIV-uninfected individuals with pulmonary TB (PTB) commonly present with radiological features of upper lobe cavitatory disease. In contrast, individuals with HIV and PTB may present differently. This study compared radiological features of individuals with laboratory-confirmed PTB by HIV status from the largest study in South Africa. Methods: We conducted a cross-sectional analysis of adults recruited between 2012 and 2015 with laboratory-confirmed PTB in Soweto, South Africa. Baseline characteristics and chest radiograph (CXR) findings were compared by χ2 test stratified by HIV status. Results: Of the 474 individuals with PTB, 348 (73.4%) had HIV. Individuals with HIV had a higher proportion of infiltrates (58.9% vs 46.8%, p=0.02) and a lower proportion of cavitations (40.8% vs 68.3%; p<0.0001) compared to HIV-uninfected individuals. Additionally, individuals with HIV had a lower proportion of cavitations sized ≥4 cm (16.7% vs 36.5%, p<0.001) and a lower proportion of disease extent involving half or more of the total lung area radiologically (25.9% vs 45.3%, p<0.0001). Conclusions: Individuals with HIV co-infected with PTB have a higher proportion of infiltrates and a lower proportion of cavitations relative to the HIV-uninfected PTB individuals. The absence of classical upper lobe cavitatory disease on CXR does not exclude PTB in individuals with HIV.

Cardiovascular Complications of HIV in Endemic Countries.

Effective combination antiretroviral therapy (ART) has enabled human immunodeficiency virus (HIV) infection to evolve from a generally fatal condition to a manageable chronic disease. This transition began two decades ago in high-income countries and has more recently begun in lower income, HIV endemic countries (HIV-ECs). With this transition, there has been a concurrent shift in clinical and public health burden from AIDS-related complications and opportunistic infections to those associated with well-controlled HIV disease, including cardiovascular disease (CVD). In the current treatment era, traditional CVD risk factors and HIV-related factors both contribute to an elevated risk of myocardial infarction, stroke, heart failure, and arrhythmias. In HIV-ECs, the high prevalence of persons living with HIV and growing prevalence of CVD risk factors will contribute to a growing epidemic of HIV-associated CVD. In this review, we discuss the epidemiology and pathophysiology of cardiovascular complications of HIV and the resultant implications for public health efforts in HIV-ECs.

HIV/AIDS-associated Kaposi's sarcoma of the gastrointestinal tract: A pictorial spectrum.

We briefly report two cases of HIV/AIDS-associated Kaposi's sarcoma affecting the gastrointestinal tract. Both patients were seen at Edenvale General Hospital, Johannesburg, South Africa.

Multiple opportunistic fungal infections in an individual with severe HIV disease: a case report / Múltiples infecciones fúngicas oportunistas en un individuo con enfermedad grave por VIH. Informe de un caso

Background. Fungal infections have been commonly diagnosed in individuals with advanced HIV disease. Cryptococcosis, pneumocystosis, and histoplasmosis are the most frequent systemic mycoses in people suffering from HIV/AIDS. Case report. We report a case of multiple fungal infections in an advanced AIDS-patient. A 33-year-old HIV-positive man from Brazil was hospitalized due to diarrhea, dyspnea, emaciation, hypoxemia, extensive oral thrush, and a CD4+ T lymphocyte count of 20 cells/mm3. Honeycombed-structures consistent with Pneumocystis jirovecii were observed by direct immunofluorescence in induced sputum. Cryptococcus neoformans was recovered from respiratory secretion and cerebrospinal fluid cultures. Histopathology of the bone marrow also revealed the presence of Histoplasma capsulatum. Molecular assays were performed in a sputum sample. Nested-PCR confirmed the presence of P. jirovecii and H. capsulatum; qPCR multiplex was positive for C. neoformans and H. capsulatum. With the treatment of antifungal drugs the patient progressed satisfactorily. Conclusions. The diagnosis of several systemic mycoses demonstrates the vulnerability of advanced AIDS-patients. Thus, the detection of AIDS cases in the early stages of infection is necessary for a prompt and adequate introduction of HAART therapy, and the use of prophylaxis to control opportunistic infections (AU)

Antecedentes. Las infecciones fúngicas se han diagnosticado comúnmente en individuos con enfermedad avanzada por VIH. La criptococosis, la neumocistosis y la histoplasmosis son las micosis sistémicas más frecuentes en personas con VIH/sida. Caso clínico. En este trabajo se describe un caso de múltiples infecciones fúngicas en un paciente con sida avanzado. Un hombre de 33 años, brasileño, con serología positiva para VIH, fue hospitalizado con pérdida de peso, diarrea, disnea, caquexia, hipoxemia, extensa candidiasis oral y recuento de linfocitos CD4+ de 20 cél./mm3. La inmunofluorescencia directa puso de manifiesto estructuras típicas compatibles con Pneumocystis jirovecii. En el cultivo de las muestras de secreción respiratoria y de líquido cefalorraquídeo creció Cryptococcus neoformans. En el análisis histopatológico de una muestra de médula ósea se observó Histoplasma capsulatum. Se llevaron a cabo ensayos de marcadores moleculares en una muestra de esputo. Se realizó un ensayo de PCR anidada que fue positivo para P. jirovecii y H. capsulatum, y una qPCR multiplex que fue positiva para C. neoformans e H. capsulatum. Con un tratamiento con antimicóticos el paciente evolucionó satisfactoriamente. Conclusiones. El diagnóstico de las micosis sistémicas demuestra la vulnerabilidad de los pacientes con sida avanzado. El diagnóstico de la infección por VIH en sus etapas iniciales es fundamental para la introducción precoz y adecuada de la terapia antirretroviral altamente activa y la profilaxis de las infecciones oportunistas (AU)

Human Immunodeficiency Virus Infection and Host Defense in the Lungs.

Immunosuppression associated with human immunodeficiency virus (HIV) infection impacts all components of host defense against pulmonary infection. Cells within the lung have altered immune function and are important reservoirs for HIV infection. The host immune response to infected lung cells further compromises responses to a secondary pathogenic insult. In the upper respiratory tract, mucociliary function is impaired and there are decreased levels of salivary immunoglobulin A. Host defenses in the lower respiratory tract are controlled by alveolar macrophages, lymphocytes, and polymorphonuclear leukocytes. As HIV infection progresses, lung CD4 T cells are reduced in number causing a lack of activation signals from CD4 T cells and impaired defense by macrophages. CD8 T cells, on the other hand, are increased in number and cause lymphocytic alveolitis. Specific antibody responses by B-lymphocytes are decreased and opsonization of microorganisms is impaired. These observed defects in host defense of the respiratory tract explain the susceptibility of HIV-infected persons for oropharyngeal candidiasis, bacterial pneumonia, Pneumocystis pneumonia, and other opportunistic infections.

Characteristics and Outcome of Patients With AIDS in Dutch ICUs Between 1997 and 2014.

OBJECTIVE: Knowledge on characteristics and outcome of ICU patients with AIDS is highly limited. We aimed to determine the main reasons for admission and outcome in ICU patients with AIDS and trends over time therein. DESIGN: A retrospective study within the Dutch National Intensive Care Evaluation registry. SETTING: Dutch ICUs. PATIENTS: We used data collected between 1997 and 2014. Characteristics of patients with AIDS were compared with ICU patients without AIDS, matched for age, sex, admission type, and admission year. Joinpoint regression analysis was applied to study trends over time. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,127 patients with AIDS and 4,479 matched controls. The main admission diagnoses of patients with AIDS were respiratory infection (28.6%) and sepsis (16.9%), which were less common in controls (7.7% and 7.5%, respectively; both p < 0.0001). Patients with AIDS had increased severity of illness and in-hospital mortality (28.2% vs 17.8%; p < 0.0001) compared with controls, which was associated with a higher rate of infections at admission in patients with AIDS (58.4% vs 25.5%). Over time, the proportion of patients with AIDS admitted with an infection decreased (75% in 1999 to 56% in 2013). Mortality declined in patients with AIDS (39% in 1999 to 16% in 2013), both in patients with or without an infection. Mortality also declined in matched controls without AIDS, but to a lesser extent. CONCLUSION: Infections are still the main reason for ICU admission in patients with AIDS, but their prevalence is declining. Outcome of patients with AIDS continued to improve during a time of widespread availability of combination antiretroviral therapy, and mortality is reaching levels similar to ICU patients without AIDS.

The immunopathogenesis of cryptococcal immune reconstitution inflammatory syndrome: understanding a conundrum.

PURPOSE OF REVIEW: Cryptococcal meningitis causes significant mortality among HIV-infected patients, despite antifungal therapy and use of antiretroviral therapy (ART). In patients with cryptococcal meningitis, ART is often complicated by immune reconstitution inflammatory syndrome (IRIS), manifesting as unmasking of previously unrecognized subclinical infection (unmasking CM-IRIS) or paradoxical worsening of symptoms in the central nervous system after prior improvement with antifungal therapy (paradoxical CM-IRIS). We review our current understanding of the pathogenesis of this phenomenon, focusing on unifying innate and adaptive immune mechanisms leading to the development of this often fatal syndrome. RECENT FINDINGS: We propose that HIV-associated CD4 T-cell depletion, chemokine-driven trafficking of monocytes into cerebrospinal fluid in response to cryptococcal meningitis, and poor localized innate cytokine responses lead to inadequate cryptococcal killing and clearance of the fungus. Subsequent ART-associated recovery of T-cell signaling and restored cytokine responses, characterized by IFN-γ production, triggers an inflammatory response. The inflammatory response triggered by ART is dysregulated because of impaired homeostatic and regulatory mechanisms, culminating in the development of CM-IRIS. SUMMARY: Despite our incomplete understanding of the immunopathogenesis of CM-IRIS, emerging data exploring innate and adaptive immune responses could be exploited to predict, prevent and manage CM-IRIS and associated morbid consequences.

Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy.

Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug-drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART.

Time to initiation of antiretroviral therapy in HIV-infected patients diagnosed with an opportunistic disease: a cohort study.

OBJECTIVES: The aim of the study was to identify factors associated with the time between opportunistic disease (OD) diagnosis and antiretroviral therapy (ART) initiation in HIV-infected patients presenting for care with an OD, and to evaluate the outcomes associated with any delay. METHODS: A multicentre cohort study was undertaken in London, Paris and Lille/Tourcoing. The medical records of patients diagnosed from 2002 to 2012 were reviewed. RESULTS: A total of 437 patients were enrolled in the study: 70% were male, the median age was 40 years, 42% were from sub-Saharan Africa, 68% were heterosexual, the median CD4 count was 40 cells/µL, and the most common ODs were Pneumocystis pneumonia (37%), tuberculosis (24%), toxoplasmosis (12%) and Kaposi's sarcoma (11%). Of these patients, 400 (92%) started ART within 24 weeks after HIV diagnosis, with a median time from OD diagnosis to ART initiation of 30 [interquartile range (IQR) 16-58] days. Patients diagnosed between 2009 and 2012 had a shorter time to ART initiation than those diagnosed in earlier years [hazard ratio (HR) 2.07; 95% confidence interval (CI) 1.58-2.72]. Factors associated with a longer time to ART initiation were a CD4 count ≥ 200 cells/µL (HR 0.30; 95% CI 0.20-0.44), tuberculosis (HR 0.40; 95% CI 0.30-0.55) and diagnosis in London (HR 0.62; 95% CI 0.48-0.80). Patients initiating 'deferred' ART (by ≥ 30 days) exhibited no difference in disease progression or immunovirological response compared with patients who had shorter times to ART initiation. Patients in the 'deferred' group were less likely to have ART modifications (HR 0.69; 95% CI 0.48-1.00) and had shorter in-patient stays (mean 14.2 days shorter; 95% CI 8.9-19.5 days) than patients in the group whose ART was not deferred. CONCLUSIONS: The time between OD diagnosis and ART initiation remains heterogeneous and relatively long, particularly in individuals with a high CD4 count or tuberculosis or those diagnosed in London. Deferring ART was associated with fewer ART modifications and shorter in-patient stays.