Immune Reconstitution Inflammatory Syndrome Research Articles

Allergy on HIV Infections: A Narrative Literature Review

HIV infection causes not only immune insufficiency but also immune dysregulation. Following HIV infection, cytokine profiles change, with a production of IL-4 rising along with IL-5 and a decrease in INF-g. This literature review aimed to describe allergy on HIV infection. At the initial phase after infection, cytokines produced by Th1 and Th2 are balanced, but later as the infection progresses, cytokines produced by Th2 will rise, while cytokines produced by Th1 will fall. Elevation of IL-4 will make B cells produce more IgE. Patients with even lower CD4 still have this allergic phenomenon caused by IgE. Allergic manifestations of HIV include rhinitis, asthma, adverse cutaneous drug reactions (ACDR), immune reconstitution inflammatory syndrome, hyperallergic state (IRIS), and atopic dermatitis. In conclusion, it is important to consider allergic manifestations even in AIDS patients, especially incidents of ACDR and IRIS, which can be life-threatening.

Successful Outcome after Treatment with Cidofovir, Vaccinia, and Extended Course of Tecovirimat in a Newly-Diagnosed HIV Patient with Severe Mpox: A Case Report

To report a case of severe mpox in a newly diagnosed HIV patient concerning for Immune Reconstitution Inflammatory Syndrome (IRIS) and/or tecovirimat resistance and to describe the management approach in the setting of refractory disease. 49-year-old man presented with 2 weeks of perianal lesions. He tested positive for mpox PCR in the emergency room and was discharged home with quarantine instructions. Three weeks later, the patient returned with disseminated firm, nodular lesions in the face, neck, scalp, mouth, chest, back, legs, arms, and rectum, with worsening pain and purulent drainage from the rectum. The patient reported being on 3 days of tecovirimat treatment, which was prescribed by the Florida department of health (DOH). During this admission, he was found to be HIV positive. A pelvic CT scan revealed a 2.5 cm perirectal abscess. Treatment with tecovirimat was continued for 14 days, along with an empiric course of antibiotics for treatment of possible superimposed bacterial infection upon discharge. He was seen in the outpatient clinic and initiated antiretroviral therapy (ART) with TAF/emtricitabine/bictegravir. Two weeks after starting ART, the patient was readmitted for worsening mpox rash and rectal pain. Urine PCR also returned positive for chlamydia, for which the patient was prescribed doxycycline. He was discharged on a second course of tecovirimat and antibiotic therapy. Ten days later, the patient was readmitted for the second time due to worsening symptoms and blockage of the nasal airway from progressing lesions. At this point, there were concerns for tecovirimat resistance, and after discussion with CDC, tecovirimat was reinitiated for the third time, with the addition of Cidofovir and Vaccinia, and showed an improvement in his symptoms. He received three doses of cidofovir and two doses of Vaccinia, and the patient was then discharged to complete 30 days of tecovirimat. Outpatient follow-up showed favorable outcomes and near resolution. We reported a challenging case of worsening mpox after Tecovirimat treatment in the setting of new HIV and ART initiation concerning IRIS vs. Tecovirimat resistance. Clinicians should consider the risk of IRIS and weigh the pros and cons of initiating or delaying ART. In patients not responding to first-line treatment with tecovirimat, resistance testing should be performed, and alternative options should be considered. Future research is needed to establish guidance on the role of Cidofovir and Vaccinia immune globulin and the continuation of tecovirimat for refractory mpox.

The Dual Benefit of Sulfasalazine on Pneumocystis Pneumonia-Related Immunopathogenesis and Antifungal Host Defense Does Not Require IL-4Rα-Dependent Macrophage Polarization.

Pneumocystis is a respiratory fungal pathogen that is among the most frequent causes of life-threatening pneumonia (PcP) in immunocompromised hosts. Alveolar macrophages play an important role in host defense against Pneumocystis, and several studies have suggested that M2 polarized macrophages have anti-Pneumocystis effector activity. Our prior work found that the immunomodulatory drug sulfasalazine (SSZ) provides a dual benefit during PcP-related immune reconstitution inflammatory syndrome (IRIS) by concurrently suppressing immunopathogenesis while also accelerating macrophage-mediated fungal clearance. The benefits of SSZ were associated with heightened Th2 cytokine production and M2 macrophage polarization. Therefore, to determine whether SSZ improves the outcome of PcP through a mechanism that requires Th2-dependent M2 polarization, RAG2-/- mice lacking interleukin 4 receptor alpha chain (IL-4Rα) on macrophage lineage cells were generated. As expected, SSZ treatment dramatically reduced the severity of PcP-related immunopathogenesis and accelerated fungal clearance in immune-reconstituted RAG2-/- mice. Similarly, SSZ treatment was also highly effective in immune-reconstituted RAG2/IL-4Rα-/- and RAG2/gamma interferon receptor (IFN-γR)-/- mice, demonstrating that neither IL-4Rα-dependent M2 nor IFN-γR-dependent M1 macrophage polarization programs were required for the beneficial effects of SSZ. Despite the fact that macrophages from RAG2/IL-4Rα-/- mice could not respond to the Th2 cytokines IL-4 and IL-13, M2-biased alveolar macrophages were identified in the lungs following SSZ treatment. These data demonstrate that not only does SSZ enhance phagocytosis and fungal clearance in the absence of macrophage IL-4Rα signaling, but also that SSZ promotes M2 macrophage polarization in an IL-4Rα-independent manner. These findings could have implications for the treatment of PcP and other diseases in which M2 polarization is beneficial.

Immune Reconstitution Inflammatory Syndrome in People Living with HIV Who Presented with Interstitial Pneumonitis: an Emerging Challenge in the Era of Rapid Initiation of Antiretroviral Therapy.

Studies on immune reconstitution inflammatory syndrome (IRIS) in people living with HIV (PLWH) and presenting with interstitial pneumonitis (IP) are limited in the era of rapid antiretroviral therapy (ART) initiation, particularly with integrase strand-transfer inhibitor (INSTI)-containing regimens. Adult PLWH presenting with IP in whom ART was initiated within 30 days of IP diagnosis between 2015 and 2021 were retrospectively identified. The primary outcome was the occurrence of IRIS within 30 days after admission. Of 88 eligible PLWH with IP (median age, 36 years; CD4 count, 39 cells/mm3), Pneumocystis jirovecii and cytomegalovirus (CMV) DNA were detected via polymerase-chain-reaction assay in 69.3% and 91.7% of respiratory specimens, respectively. 22 PLWH (25.0%) had manifestations that met French's IRIS criteria for paradoxical IRIS. There were no statistically significant differences in terms of the all-cause mortality (0.0% versus 6.1%, P = 0.24), the occurrence of respiratory failure (22.7% versus 19.7%, P = 0.76), and pneumothorax (9.1% versus 7.6%, P = 0.82) between PLWH with and those without paradoxical IRIS. In a multivariable analysis, the factors associated with IRIS were the decline of the 1 month plasma HIV RNA load (PVL) with ART (adjusted hazard ratio [aHR] per 1 log decrease, 3.45; 95% CI, 1.52 to 7.81), a baseline CD4-to-CD8 ratio of <0.1 (aHR, 3.47; 95% CI, 1.16 to 10.44), and the rapid initiation of ART (aHR, 7.95; 95% CI, 1.04 to 60.90). In conclusion, we found a high rate of paradoxical IRIS among PLWH with IP in the era of rapid ART initiation with INSTI-containing ART and this was associated with immune depletion at baseline, a rapid decline of PVL, and an interval of <7 days between the diagnosis of IP and the initiation of ART. IMPORTANCE Our study of PLWH who presented with IP mainly due to Pneumocystis jirovecii demonstrates that a high rate of paradoxical IRIS and a rapid decline of PVL with the initiation of ART, a CD4-to-CD8 ratio of <0.1 at baseline, and a short interval (<7 days) between the diagnosis of IP and the initiation of ART were associated with paradoxical IP-IRIS in PLWH. Paradoxical IP-IRIS was not associated with mortality or respiratory failure with heightened awareness among the HIV-treating physicians, rigorous investigations to exclude the possibilities of concomitant infections, or the malignancies and adverse effects of medications, including the cautious use of corticosteroids.

Epidemiology, management and outcomes of Cryptococcus gattii infections: A 22-year cohort.

Cryptococcus gattii is a globally endemic pathogen causing disease in apparently immune-competent hosts. We describe a 22-year cohort study from Australia's Northern Territory to evaluate trends in epidemiology and management, and outcome predictors. A retrospective cohort study of all C. gattii infections at the northern Australian referral hospital 1996-2018 was conducted. Cases were defined as confirmed (culture-positive) or probable. Demographic, clinical and outcome data were extracted from medical records. 45 individuals with C. gattii infection were included: 44 Aboriginal Australians; 35 with confirmed infection; none HIV positive out of 38 tested. Multifocal disease (pulmonary and central nervous system) occurred in 20/45 (44%). Nine people (20%) died within 12 months of diagnosis, five attributed directly to C. gattii. Significant residual disability was evident in 4/36 (11%) survivors. Predictors of mortality included: treatment before the year 2002 (4/11 versus 1/34); interruption to induction therapy (2/8 versus 3/37) and end-stage kidney disease (2/5 versus 3/40). Prolonged antifungal therapy was the standard approach in this cohort, with median treatment duration being 425 days (IQR 166-715). Ten individuals had adjunctive lung resection surgery for large pulmonary cryptococcomas (median diameter 6cm [range 2.2-10cm], versus 2.8cm [1.2-9cm] in those managed non-operatively). One died post-operatively, and 7 had thoracic surgical complications, but ultimately 9/10 (90%) treated surgically were cured compared with 10/15 (67%) who did not have lung surgery. Four patients were diagnosed with immune reconstitution inflammatory syndrome which was associated with age <40 years, brain cryptococcomas, high cerebrospinal fluid pressure, and serum cryptococcal antigen titre >1:512. C. gattii infection remains a challenging condition but treatment outcomes have significantly improved over 2 decades, with eradication of infection the norm. Adjunctive surgery for the management of bulky pulmonary C. gattii infection appears to increase the likelihood of durable cure and likely reduces the required duration of antifungal therapy.

Mpox in people with advanced HIV infection: a global case series

People living with HIV have accounted for 38-50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30-43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117-291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100-200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. None.

A Functional Polymorphism in IL-1B Is Associated With Immune Reconstitution Inflammatory Syndrome of Chronic Disseminated Candidiasis.

We investigated single nucleotide polymorphisms (SNPs) possibly involved in immune reconstitution inflammatory syndrome of chronic disseminated candidiasis (IRIS-CDC) through a candidate gene approach and a prospective matched-control study. We found that an SNP located in interleukin-1B at rs1143627 was significantly associated with the risk of developing IRIS-CDC.

A case of apparent ART-associated immune reconstitution inflammatory syndrome in a patient with Strongyloides stercoralis infection

Introduction: Strongyloides infection is most commonly caused by Strongyloides stercoralis (S. stercoralis). It often causes asymptomatic chronic infection but through the translocation of the parasite into the bloodstream, it can lead to disseminated strongyloidiasis (DS). We describe a case of a patient with human immunodeficiency virus (HIV) who developed Strongyloidiasis with the complication of vancomycin-resistant Enterococcus (VRE) meningitis. Notably, the clinical condition of the patient worsened after commencing anti-retroviral therapy (ART), raising concern for ART-associated immune reconstitution inflammatory syndrome (IRIS) to S. stercoralis. Case Report: A 51-year-old African female with a past medical history of HIV presented with a 1-week history of abdominal pain and a 2-month history of generalized malaise, constipation, and weight loss. She improved with symptomatic management and commenced Biktarvy. She re-presented one month later with worsening gastrointestinal symptoms. Her hospital course was complicated by septicemia with worsening mentation. Her repeat abdominal imaging showed ascending and transverse colitis and cerebrospinal fluid analysis was positive for vancomycin-resistant Enterococcus faecium (VRE). During her re-admission, the patient developed persistent watery diarrhea which was found to be positive for S. stercoralis. Despite medical therapy she demised on day 28 of admission. Conclusion: Literature is very scarce concerning the progression of S. stercoralis infection to Strongyloides disseminated strongyloidiasis (DS) as a result of IRIS. As clinicians, we must have a high index of suspicion in our HIV population as DS can lead to fatal complications. It can also help guide management decisions concerning ART until complete eradication of S. stercoralis infection is obtained.

Prognostic factors for immune reconstitution inflammatory syndrome in patients with HIV and tuberculosis during antiretroviral therapy

Antiretroviral therapy (ARVT) promotes the growth of a CD4 lymphocyte subpopulation, which leads to the development of immune reconstitution inflammatory syndrome (IRIS) in a number of patients with late-stage HIV and tuberculosis (TB) coinfection. Early prognostic factors for IRIS should be identified to timely initiate pathogenetic therapy aimed at its relief and ARVT continuation. Objective. To develop a method for the early diagnosis of IRIS in patients with HIV/TB coinfection during ARVT and to identify criteria for initiating pathogenetic therapy. Subjects and methods. The investigation enrolled 200 patients with HIV/TB coinfection who were divided into 2 groups: 1) 100 patients who received antituberculosis therapy (ATBT) without ARVT; 2) 100 patients who had combination (ARVT + ATBT) treatment. A control group included 50 healthy volunteers. To determine the prognostic factors for IRIS, all the patients underwent studies of viral load, CD4 lymphocyte levels, plasma lipid profile, and a complete blood count with a differential blood count before and after 1 month of treatment. Results. In Group 2, the signs of IRIS were detected in 30 (30%) patients; those were absent in 70 (70%) patients at 10-14 days after the start of combination (ARVT + ATBT) therapy. The level of stab neutrophils was significantly higher in patients with the signs of IRIS than in those without IRIS, despite the absence of a difference in viral load and CD4 lymphocyte levels (p&gt;0.05). All the patients with HIV/TB coinfection showed changes in the indicators of the lipid spectrum. However, there were significant differences between the patients with and without IRIS only in the level of triglycerides (TG) (1.4±0.2 and 0.9±0.2 mmol/l, respectively; p&lt;0.001). Timely detoxification therapy for patients with the signs of IRIS (manifestations of intoxication syndrome and elevated TG levels) resulted in the relief of this syndrome, which made it possible to continue ARVT. Conclusion. The significant increase in the level of TG in patients with the signs of IRIS during ARVT + ATBT allows this indicator to be used as an early laboratory marker of the risk for IRIS to timely prescribe pathogenetic therapy and to continue ARVT, which is important in predicting the disease.

Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome-An Extempore Game of Misfiring with Defense Arsenals.

The lethal combination involving TB and HIV, known as "syndemic" diseases, synergistically act upon one another to magnify the disease burden. Individuals on anti-retroviral therapy (ART) are at risk of developing TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The underlying inflammatory complication includes the rapid restoration of immune responses following ART, eventually leading to exaggerated inflammatory responses to MTB antigens. TB-IRIS continues to be a cause of morbidity and mortality among HIV/TB coinfected patients initiating ART, and although a significant quantum of knowledge has been acquired on the pathogenesis of IRIS, the underlying pathomechanisms and identification of a sensitive and specific diagnostic marker still remain a grey area of investigation. Here, we reviewed the latest research developments into IRIS immunopathogenesis, and outlined the modalities to prevent and manage strategies for better clinical and diagnostic outcomes for IRIS.

A retrospective clinical study of dolutegravir- versus efavirenz-based regimen in treatment-naïve patients with advanced HIV infection in Nanjing, China.

Currently, there are limited data related to the efficacy and safety of ART regimens, as well as factors influencing immune recovery in antiretroviral therapy (ART)-naïve patients with advanced HIV infection, especially in China. We designed a single-center, retrospective cohort study from March 1, 2019, to May 31, 2022, at The Second Hospital of Nanjing, China. ART-naïve adults with advanced HIV infection (CD4+ T-cell count < 200 cells/μL) who met the study criteria were included. The plasma viral load (VL), CD4+ T-cell count, CD4/CD8 ratio, treatment discontinuation, and immune reconstitution inflammatory syndrome (IRIS) events were collected to compare the efficacy and safety of the dolutegravir (DTG) and the efavirenz (EFV) regimens. Factors of immune recovery were analyzed using the Cox regression model. Study enrolled 285 ART-naïve adults with advanced HIV-1 infection, of which 95 (33.3%) started regimens including DTG and 190 (66.7%) were treated with EFV. After ART initiation, the proportion of patients with HIV-1 RNA < 50 copies/mL was higher (22.5% versus 6.5%, P < 0.001) in those on DTG-based regimens at month 1, but no significant difference at other follow-up points. Compared to the baseline, the median CD4+ T-cell count and CD4/CD8 ratio increased significantly during follow-up both in the EFV and the DTG groups. However, the CD4+ T-cell count increased greater in patients on DTG-based regimens at months 6, 12, 24, and 36 (P < 0.05). A total of 52 (18.2%) patients discontinued treatment, with no significant difference between ART regimens in treatment discontinuation rates. Only 7 patients reported IRIS, without significant difference between ART regimens (P=0.224). Overall, 34.0% (97/285) achieved a CD4+ T-cell count ≥ 350 cells/μL during follow-up. Age (P < 0.001), baseline CD4+ T-cell count (P < 0.001), baseline VL (P < 0.001) and ART regimens (P = 0.019) were associated with the CD4+ T-cell count ≥ 350 cells/μL after adjusting for potential confounders. Among ART-naïve adults with advanced HIV infection, it appeared that DTG-based regimens were better options for initial therapy compared to regimens including EFV; in addition, ART regimens, age, baseline VL and CD4+ T-cell count were associated with immune recovery.

Therapy initiation and rapid start with Bictegravir/Emtricitabine/Tenofovir Alafenamide in PLWH.

Advanced HIV naive represents an unfavorable prognostic condition due to a persistent high risk of death, increased probability of virological failure, immunologic impairment, clinical progression, and immune reconstitution inflammatory syndrome (IRIS), cumulative adverse drug events, drug-drug interactions and increased healthcare costs. Currently, all international guidelines recommend the rapid initiation of ART, especially in late-stage naive patients. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), due to its efficacy high genetic barrier, good safety profile, and low DDI potential, is one of the regimens recommended for overall rapid initiation by international guidelines. B/F/TAF has been tested in observational or uncontrolled pilot studies (OPERA, RAINBOW), while a large randomized controlled trial is currently ongoing (LAPTOP). In conclusion, B/F/TAF is an ideal combination for the initiation of antiretroviral therapy, particularly in the HIV late presenter or advanced HIV disease patient, even in the context of rapid start or same-day treatment regimens, where the initiation of treatment usually occurs in the absence of information on viral load, CD4 count, biochemical profile and HIV transmitted resistance.

Immunological Analysis of Cryptococcal Meningoencephalitis in a Murine Model.

Cryptococcal meningoencephalitis (CM), caused by the fungal pathogen Cryptococcus neoformans species complex, can lead to high mortality or severe neurological sequelae in survivors that are associated with excessive inflammation in the central nervous system (CNS), especially in those who develop immune reconstitution inflammatory syndrome (IRIS) or postinfectious immune response syndrome (PIIRS). While the means to establish a cause-and-effect relationship of a specific pathogenic immune pathway during CM by human studies are limited, mouse models allow dissection of the potential mechanistic links within the CNS immunological network. In particular, these models are useful for separating pathways contributing predominantly to immunopathology from those important for fungal clearance. In this protocol, we described methods to induce a robust, physiologically relevant murine model of C. neoformans CNS infection that reproduces multiple aspects of human cryptococcal disease immunopathology and subsequent detailed immunological analysis. Combined with tools including gene knockout mice, antibody blockade, cell adoptive transfer, as well as high throughput techniques such as single-cell RNA sequencing, studies using this model will provide new insights regarding the cellular and molecular processes that elucidate the pathogenesis of cryptococcal CNS diseases in order to develop more effective therapeutic strategies.

Differential diagnosis of immune reconstitution inflammatory syndrome and progressive multifocal leukoencephalopathy after natalizumab withdrawal

The appearance of new foci on MRI, the increase in neurological deficits, including the appearance of cognitive disorders and disturbances in the level of consciousness in patients with multiple sclerosis during the «washing period» when transferring from natalizumab (NZ) to another drug, may be due to both progressive multifocal leukoencephalopathy (PML) and exacerbation of the disease in the absence of therapy. Discontinuation of NS is fraught not only with a resumption, but with an increase in disease activity, the development of an immune reconstitution inflammatory syndrome (IRIS) due to the opening of the blood-brain barrier. Often, the processes of differential diagnosis of IRIS and natalizumab-associated PML are complex and require the use of additional methods of examination and monitoring of the dynamics of the patient's condition. However, the severity of the condition and the severity of the consequences caused by incorrect therapeutic tactics significantly reduce the time for diagnosis and require an immediate decision. The difficulties of differential diagnosis of IRIS and PML are reflected in the clinical case.

Genetic Mouse Models of Pneumocystis Pneumonia.

Pneumocystis jirovecii causes pneumonia in immunocompromised patients. A major challenge in drug susceptibility testing and in understanding host/pathogen interactions is that Pneumocystis spp. are not viable in vitro. Continuous culture of the organism is not currently available, and therefore, developing new drug targets is very limited. Due to this limitation, mouse models of Pneumocystis pneumonia have proven to be an invaluable resource to researchers. In this chapter, we provide an overview of selected methods used in mouse models of infection including, in vivo Pneumocystis murina propagation, routes of transmission, genetic mouse models available, a P. murina life form-specific model, a mouse model of PCP immune reconstitution inflammatory syndrome (IRIS), and the experimental parameters associated with these models.

Neuropsychiatric sequelae of medication non-adherence in people living with HIV

&lt;abstract&gt; &lt;p&gt;Non-adherence to anti-retroviral therapy (cART) among people living with HIV/AIDS (PLWHA) is complex, multifactorial, and leads to increases in viral load, immunosuppression, and HIV burden related to direct CNS virulence and cART re-initiation (i.e., immune reconstitution syndrome). Among behavioral disturbances, which may become long-lasting without proper treatment, major depressive disorder, generalized anxiety disorder, schizophrenia, and bipolar spectrum disorders are frequent, as well as exacerbation of other premorbid underlying psychiatric conditions, such as post-traumatic stress disorder (PTSD) and substance use and related conditions, not to mention neurocognitive disorders that are encompassed under the umbrella term of HIV-Associated Neurocognitive Disorders (HAND). In this review, we summarized the neuropsychiatric sequelae of medication non-adherence in PLWHA by utilizing two clinical vignettes to illustrate how syndemic factors may interact and lead to unique presentations.&lt;/p&gt; &lt;/abstract&gt;

Three Probable Cases of Immune Reconstitution Inflammatory Syndrome Manifesting as Type 1 Diabetes Mellitus during Treatment of HIV Infection

Three Probable Cases of Immune Reconstitution Inflammatory Syndrome Manifesting as Type 1 Diabetes Mellitus during Treatment of HIV Infection

Chronic Anogenital Ulcerations and Polymicrobial Pelvic Infections: About a Case

Genital ulceration is the loss of integrity of the mucous membranes (or genital skin) leaving the dermis uncovered and almost always accompanied by satellite lymphadenopathies. Beyond a month of evolution, it is said to be chronic. Sexually transmitted diseases are infections due to microbial agents among which parasites, bacteria, viruses and fungi that can be associated with each other to varying degrees. Sexually transmitted infections must be mentioned before any genital ulceration. Hence the interest of the case that we report of chronic anogenital ulcerations complicating a polymicrobial pelvic infection in a patient immunocompromised to HIV. The physical examination reveals a hypogastric sensitivity to deep palpation, the presence of a superinfected anogenital ulceration exposing the deep dermis covered with purulent serosities interesting the labia minora, the posterior vaginal fork, the anal region, the clitoris and an extension of the lesions to the gluteal fold is observed. We found a satellite lymphadenopathy in the right inguinal fold. The screening finds the HIV1 positive serology with a viral load of 28,000 copies, the herpes simplex 1&2 and Chlamydia trachomatis serologies were all positive. The genital samples are marked by the presence of bacterial vaginosis with Candida Albicans and Gardnerella Vaginalis, the presence of urogenital mycoplasmas of the Ureaplasma Urealyticum The pelvic ultrasound was in favor of a bilateral adnexitis. A protocol was put in place: the first step consisted of seat baths, antifungi and antibiotics administration: fluconazole 150 mg and tinidazole 2 g in single doses, then josamycin 1 g/24h in two doses per os for two weeks. The second stage consists of the administration of doxycycline 200 mg for 21 days, Aciclovir 500 mg for 10 days, and the administration of ARV (Tenofovir + Lamivudine + Dolutegravir) or one tablet daily. The evolution is marked by a progressive healing of the clitoris, the labia majora and labia minora, the posterior vaginal fork. In case of chronicity, a biopsy in search of a tumor process is not mandatory when there is a satisfactory response to treatment and good healing. The patient’s death two weeks after the beginning of ARV treatment, can be explained by a probable immune reconstitution syndrome.

Clinical Worsening in an Adolescent With Pleural Tuberculosis

A 17-year-old previously healthy female presented with unilateral chest pain and dyspnea. Chest radiographs demonstrated a unilateral pleural effusion and pneumonia. Pleural fluid bacterial cultures were negative; acid-fast cultures grew Mycobacterium tuberculosis. Two months after starting appropriate therapy, she had a recrudescence of symptoms and reaccumulation of the pleural fluid. Her tuberculosis antibiotic regimen was expanded, the effusion drained, and systemic corticosteroids initiated, resulting in rapid clinical improvement. Cultures of the second pleural fluid collection were negative. Her clinical deterioration was due to immune reconstitution inflammatory syndrome (IRIS). IRIS can be seen within the first several months of starting tuberculosis therapy and can result in paradoxical worsening of symptoms or radiographic findings in adolescents who are on the appropriate therapy. IRIS is a diagnosis of exclusion after drug resistance and medication malabsorption, intolerance, and nonadherence are excluded. Therapy includes nonsteroidal anti-inflammatory agents for milder reactions and systemic corticosteroids for more severe IRIS cases.

Meningeal Sporotrichosis Due to Sporothrix brasiliensis: A 21-Year Cohort Study from a Brazilian Reference Center.

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan-Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.