Advanced HIV Disease Research Articles

Decrease in late presentation for HIV care in Kinshasa, DRC, 2006\u20132020

IntroductionLate presentation for HIV care is a well-described issue for the success of ART outcomes and the cause of higher morbidity, mortality and further transmission. Monitoring the level of late presentation and understanding the factors associated with it would help to tailor screening and information strategies for better efficiency.We performed a retrospective cohort study in Kinshasa, the capital of the DRC. The studied population included HIV-positive adults newly enrolled in HIV care between January 2006 and June 2020 at 25 HIV urban care facilities. Patient information collected at presentation for HIV care included age, sex, WHO clinical stage and screening context. We used 2 definitions of late presentation: the WHO definition of advanced HIV disease (WHO stage 3/4 or CD4 cell count < 200 cells/mm3) and a more inclusive definition (WHO stage 3/4 or CD4 cell count < 350 cells/mm3).ResultsA total of 10,137 HIV-infected individuals were included in the analysis. The median age was 40 years; 68% were female. A total of 45.9% or 47.5% of the patients were late presenters, depending on the definition used. The percentage of patients with late presentation (defined as WHO stage 3/4 or CD4 cell count < 350 cells/mm3) decreased during recent years, from 70.7% in 2013 to 46.5% in 2017 and 23.4% in 2020. Age was associated with a significantly higher risk of LP (p < 0.0001). We did not observe any impact of sex.ConclusionsThe frequency of late presentation for care is decreasing in Kinshasa, DRC. Efforts have to be continued. In particular, the issue of late diagnosis in older individuals should be addressed.

Association of semi-quantitative cryptococcal antigen results in plasma with subclinical cryptococcal meningitis and mortality among patients with advanced HIV disease.

We evaluated two single-step laboratory tests that can quantify the amount of cryptococcal antigen in plasma of patients with advanced HIV disease and could thus gauge the risk of concurrent cryptococcal meningitis and subsequent mortality. These tests are not a substitute for a lumbar puncture.

Mortality predictive factors of people living with human immunodeficiency virus and bloodstream infection

IntroductionPortugal has one of the highest mortality rates for people living with HIV (PLWHIV) in Europe. After antiretroviral therapy introduction, HIV-associated mortality declined, included the one associated with bloodstream infection (BSI). However it is still high, and European data are scarce . Therefore, characterizing BSI and defining prognostic factors may improve our approach. MethodsThis was a 10-year retrospective study of predictive factors for 30-day and 3-year mortality in PLWHIV with BSI in a tertiary infectious diseases ward. ResultsOf 2134 PLWHIV admissions, 145 (6.8%) had a BSI, mostly respiratory and catheter-related bacteremia and globally community-acquired. Nosocomial infections occurred in 42 (36%) cases, mostly caused by Enterococcus spp, Staphylococcus aureus, and Candida spp. PLWHIV with a BSI had higher 30-day mortality (27%) compared to those without a BSI (14%). APACHE II score, corticotherapy, and current intravenous drug use (IDU) had a prognostic impact on 30-day mortality. Three-year survival was 54% in PLWHIV with a BSI; a CD4 <200 cells, vascular or chronic pulmonary disease, and lymphoma were prognostic factors. ConclusionsPatients with a BSI were more likely to present advanced HIV disease, have more comorbidities, a longer length of stay, and higher 30-day mortality. IDU and severity of infection determined the short-term prognosis. Three-year mortality was primarily influenced by lower CD4 cell counts, hematological tumor, and cardiopulmonary comorbidities. Systemic corticotherapy may influence nosocomial BSI and short-term prognosis.

Socio-demographic Determinants of Undernutrition In HIV- Infected Under- Five Children

Background: The disease burden associated with HIV/AIDS is a key factor in the etiopathogenesis of undernutrition in growing children. This is aggravated by resultant social factors in HIV such as orphaning, low socioeconomic status, food insecurity, and marital status of caregivers.&#x0D; Objectives: The relationship between sociodemographic factors and malnutrition in the background of HIV was evaluated.&#x0D; Methods: A cross-sectional descriptive survey was conducted among under-five HIV positive children in Anambra State, Nigeria.&#x0D; Results: A total of 370 HIV positive under-five children comprising 208(56.2%) males and 162(43.8%) females were recruited. The mean age of the children was 44.5±12.9 months. One hundred and forty-seven (39.7%) were globally undernourished: 15.7.0% (58) underweight (WFA &lt;-2SD), 13.3% (49) wasted (WFH &lt; -2SD), and 27.9% (103) stunted (HFA &lt;-2SD). Males were significantly more stunted than females (p&lt;0.001). 77% (285) were of low socioeconomic class (SEC), 47.3% (175) had advanced HIV disease, and 68.1% (252) had been on HAART for &gt;12 months. 26% (96) were orphans, while 28.6% (106) were cared for by single parents. Being on HAART for &gt;12 months was associated with less undernutrition, while advanced HIV disease seemed to enhance it. Children of low SEC were more likely to be undernourished. Not having been breastfed, introduction of complementary feeds at age 3mo or less, poor food variety and suboptimal feeding frequency increased susceptibility to undernutrition. Orphans were more wasted and stunted than underweight. Single parenthood predisposed to undernutrition.&#x0D; Conclusions: HIV-infected children are vulnerable to malnutrition by virtue of the disease process, further compounded by interwoven social dilemma associated with HIV. It, therefore, behooves the health care provider to ensure a proactive growth monitoring and nutritional support, with prompt treatment of co-morbid debilitating infections. There is also a dire need for public health interventions targeted at single parents of low socioeconomic means.

Survival following screening and preemptive antifungal therapy for subclinical cryptococcal disease in advanced HIV infection.

Our study's primary objective was to compare 1-year survival rates between serum cryptococcal antigen (sCrAg)-positive and sCrAg-negative HIV-positive individuals with CD4+ cell counts less than 100 cells/μl without symptoms of meningitis in Zimbabwe. This was a prospective cohort study. Participants were enrolled as either sCrAg-positive or sCrAg-negative and followed up for 52 weeks or less, with death as the outcome. Lumbar punctures were recommended to all sCrAg-positives and inpatient management with intravenous amphotericin B and high-dose fluconazole was recommended to those with disseminated Cryptococcus. Antiretroviral therapy was initiated immediately in sCrAg-negatives and after at least 4 weeks following initiation of antifungals in sCrAg-positives. Multivariable logistic regression models were used to determine risk factors for mortality. We enrolled 1320 participants and 130 (9.8%) were sCrAg positive, with a median sCrAg titre of 1 : 20. Sixty-six (50.8%) sCrAg-positives had lumbar punctures and 16.7% (11/66) had central nervous system (CNS) dissemination. Cryptococcal blood cultures were performed in 129 sCrAg-positives, with 10 (7.8%) being positive. One-year (48-52 weeks) survival rates were 83.9 and 76.1% in sCrAg-negatives and sCrAg-positives, respectively, P = 0.011. Factors associated with increased mortality were a positive sCrAg, CD4+ cell count less than 50 cells/μl and having presumptive tuberculosis (TB) symptoms. Our study reports a high prevalence of subclinical cryptococcal antigenemia and reiterates the importance of TB and a positive sCrAg as risk factors for mortality in advanced HIV disease (AHD). Therefore, TB and sCrAg screening remains a crucial component of AHD package, hence it should always be part of the comprehensive clinical evaluation in AHD patients.

Predictors of Current CD4+ T-Cell Count Among Women of Reproductive Age on Antiretroviral Therapy in Public Hospitals, Southwest Ethiopia.

BackgroundHIV/AIDS is one of the major global public health problems. CD4 is a glycoprotein found on the surface of different immune cells. CD4 cell counts determine the need for screening and prophylactic interventions against common opportunistic infections in those with advanced HIV disease. Thus, this study aimed to assess the predictors of current CD4+ T-cell count among women of reproductive age on antiretroviral therapy in public hospitals, southwest Ethiopia.MethodsA cross-sectional study was conducted from February to April 2018. A total of 422 participants in the three public hospitals were selected using a systematic random sampling method. Linear regression analyses were used to determine the important predictors of current CD4+ T-cell count at p-values of <0.05.ResultsA total of 422 women with a median age of 37.00 years participated in this study. More than one in ten (12.8%) respondents experienced immunological failure. An increased current CD4+ T-cell count was observed among patients with a tertiary level of education [β = 56.45, 95% CI (3.5, 109.4)], baseline WHO clinical stage II [β = 44.06, 95% CI (5.3, 82.9)], initial regimen of AZT+3TC+EFV [β = 167.23, 95% CI (100.4, 234.1)], with increased baseline CD4+ T-cell count [β = 0.35, 95% CI (0.2, 0.5)], and with increased time duration on ART [β = 14.36, 95% CI (6.304, 22.4)]. On the other hand, the current CD4+ T-cell count was lowered among patients with poor baseline adherence, opportunistic infection, and viral load of ≥1000 by 181.06 cells/mm3, 101.62 cells/mm3, and 137.53 cells/mm3 compared to good baseline adherence, no opportunistic infection and undetectable viral load, respectively.ConclusionThe immunological failure was relatively low. Maintaining adherence, early identification and treatment of opportunistic infections, and minimizing viral load to undetectable levels may further decrease immunological failure.

Timeliness of antiretroviral therapy initiation in the era before universal treatment

We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1–Q3: 29.6–43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days–1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA < 50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005–2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.

Predictors of Rifampicin-Resistant Tuberculosis Mortality among HIV-Coinfected Patients in Rwanda.

.Tuberculosis (TB), including multidrug-resistant (MDR; i.e., resistant to at least rifampicin and isoniazid)/rifampicin-resistant (MDR/RR) TB, is the most important opportunistic infection among people living with HIV (PLHIV). In 2005, Rwanda launched the programmatic management of MDR/RR-TB. The shorter MDR/RR-TB treatment regimen (STR) has been implemented since 2014. We analyzed predictors of MDR/RR-TB mortality, including the effect of using the STR overall and among PLHIV. This retrospective study included data from patients diagnosed with RR-TB in Rwanda between July 2005 and December 2018. Multivariable logistic regression was used to assess predictors of mortality. Of 898 registered MDR/RR-TB patients, 861 (95.9%) were included in this analysis, of whom 360 (41.8%) were HIV coinfected. Overall, 86 (10%) patients died during MDR/RR-TB treatment. Mortality was higher among HIV-coinfected compared with HIV-negative TB patients (13.3% versus 7.6%). Among HIV-coinfected patients, patients aged ≥ 55 years (adjusted odds ratio = 5.89) and those with CD4 count ≤ 100 cells/mm3 (adjusted odds ratio = 3.77) had a higher likelihood of dying. Using either the standardized longer MDR/RR-TB treatment regimen or the STR was not correlated with mortality overall or among PLHIV. The STR was as effective as the long MDR/RR-TB regimen. In conclusion, older age and advanced HIV disease were strong predictors of MDR/RR-TB mortality. Therefore, special care for elderly and HIV-coinfected patients with ≤ 100 CD4 cells/mL might further reduce MDR/RR-TB mortality.

Combining urine antigen and blood polymerase chain reaction for the diagnosis of disseminated histoplasmosis in hospitalized patients with advanced HIV disease.

In this prospective cohort study carried-out in a referral center in São Paulo, Brazil, we found a high frequency of AIDS-related disseminated histoplasmosis (8/106, 7.5%). We used urine antigen test and blood PCR assay to improve the diagnosis of this opportunistic disease.

SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?

SARS-CoV-2 Vaccines in Kidney Transplant Recipients: Will They Be Safe and Effective and How Will We Know?

Pneumocystis jirovecii Pneumonia Mimicking COVID-19 Pneumonia In A Patient With Newly Diagnosed Advanced HIV Disease

During the pandemic, diagnosis of COVID-19 infection must be excluded in patients presenting with respiratory features, especially in the area where the incidence was high. This case report highlights a man who came with respiratory infection symptoms and the chest radiograph suspicious of COVID-19 pneumonia; however, his swab test for RT-PCR was negative for COVID-19. Later he was found to have a positive anti-HIV antibody and developed advanced HIV infection by multiple opportunistic infections. A 45-year-old man presented with chronic cough and dyspnea for three months which worsened five days before the presentation. It was associated with diarrhoea, dysphagia, weight loss, left lower limb weakness, with bowel and urinary incontinence. Chest auscultation revealed generalized crepitations. The first chest radiograph showed bilateral reticular opacities extending to the lung peripheries when the suspected diagnosis of COVID-19 pneumonia was made. The nasopharynx swab for RT-PCR for COVID-19 was negative, and the sputum was positive for Pneumocystis jirovecii. The contrast-enhanced CT (CECT) brain revealed changes consistent with brain abscess. The cerebrospinal fluid (CSF) examination was consistent with cryptococcal infection. He was initially treated in the Severe Acute Respiratory Infection (SARI) ward because of the initial impression of COVID-19. He was tested positive for Human Immunodeficiency Virus (HIV) rapid test and PCR, RPR and TPHA for syphilis. He was diagnosed with Pneumocystis jirovecii pneumonia, cryptococcal meningitis, brain abscess, oral and oesophageal candidiasis and syphilis. He was treated with co-trimoxazole, Amphotericin B, flucytosine, fluconazole, penicillin G and Nystatin. He initially improved upon treatment but later succumbed to his illnesses. Given the current situation of COVID-19, any patient with acute respiratory symptoms must be tested to rule out COVID-19 pneumonia. However, in a newly diagnosed advanced HIV patient presented with respiratory infection symptoms and extrapulmonary symptoms, opportunistic infections should be excluded along with COVID-19.

High prevalence of Cryptococcal antigenemia using a finger-prick lateral flow assay in individuals with advanced HIV disease in Santarém Municipality, Brazilian Amazon Basin.

There is scarce information about HIV-related cryptococcosis in the Brazilian Amazon basin where laboratory infrastructure is limited. The serum cryptococcal antigen (CrAg) lateral flow assay (LFA) has simplified diagnosis of cryptococcosis and is recommended for screening in advanced HIV disease. We evaluated the prevalence of cryptococcal antigenemia using finger-prick CrAg LFA in the Brazilian Amazon basin. We enrolled a prospective cohort of outpatients and hospitalized individuals with advanced HIV disease at two centers in Santarém Municipality, Northern Brazil. All individuals were>18 years old with advanced HIV disease, regardless of antiretroviral therapy (ART) status and with no prior or current history of confirmed cryptococcal meningitis. We tested CrAg LFA on finger-prick whole blood using an exact volume transfer pipette. From August 2018 to October 2019, 104 individuals were enrolled (outpatients 62 [60%] and hospitalized 42 [40%]). Median age was 38 years (interquartile range [IQR] 30-46), and 84 (81%) were male. Sixty-five (63%) individuals were ART-naïve. Prevalence of finger-prick CrAg LFA-positive was 10.6%; 95% CI, 5.4 to 18.1%. Prevalence of finger-prick CrAg LFA-positive among individuals without neurological symptoms was 6.0%; 95% CI, 1.7-14.6%. The number needed to test to detect one CrAg-positive individual was 9.4 persons (95% CI, 5.5-18.5). Prevalence of cryptococcal antigenemia using finger-prick whole blood CrAg LFA was high. Point-of-care approach was important for the diagnosis and screening of cryptococcosis in resource-limited settings. Screening and preemptive therapy strategy should be urgently implemented in individuals with advanced HIV disease in the Brazilian Amazon basin.

A Rapid Screening Program for Histoplasmosis, Tuberculosis, and Cryptococcosis Reduces Mortality in HIV Patients from Guatemala.

Opportunistic infections (OIs) and advanced HIV disease (AHD) contribute to HIV-related mortality. Here, we analyzed the situation of AHD and OIs in a cohort of newly diagnosed HIV patients from Guatemala. We included 2127 adult patients from 13 facilities across the country during 2017 to 2018. Patients were screened for tuberculosis (TB), nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcal disease, independently of their CD4 cell count. Of the 2127 enrolled patients, 1682 (79.1%) had a CD4 cell count available; of which 52% presented with AHD. Of the Mayan population, 65% had AHD. The overall OI incidence was 21%. Histoplasmosis was the most frequent OI (7.9%), followed by TB (7.1%); 94.4% of these infections occurred in patients with a CD4 < 350 cells/mm3. Mortality at 180 days was significantly higher in those with OIs than without OIs (29.7% vs. 5.9%, p < 0.0001). In one year, this program decreased the OI mortality by 7% and increased the OI treatment by 5.1%. Early OI diagnosis and appropriate therapy reduced OI mortality among newly diagnosed HIV patients in Guatemala. Screening for OIs should be considered in all newly diagnosed HIV patients who have a CD4 cell count < 350 cells/mm3 or those without a CD4 cell count available. To improve results, interventions such as early HIV detection and access to flucytosine and liposomal amphotericin B are required.

Infecciones fúngicas en pacientes con COVID-19

En diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus denominado SARS-CoV-2, agente causal de la epidemia de neumonía atípica COVID-2019, que el 11 de marzo de 2020 fue declarada pandemia por la OMS.&#x0D; Hasta el 30 de septiembre de 2020, en Argentina fueron confirmados 751.001 casos y más de 16.937 muertes.La frecuencia y el impacto de las coinfecciones que afectan a los pacientes infectados por SARS-Cov-2 se ha estudiado junto con el avance de la pandemia. Entre las debidas a hongos se encuentran las fungemias por Candida sp, la aspergilosis invasora, las micosis sistémicas endémicas y la neumocistosis.&#x0D; Presentamos las distintas coinfecciones micosis-COVID-19 que fueron asistidas en nuestra institución entre abril y septiembre de 2020, y se realiza un análisis de las características de estas infecciones en pacientes con y sin sida. En este período se internaron 2837 pacientes, 2287 tuvieron diagnóstico confirmado de COVID-19. La coinfección de COVID-19 con micosis pulmonares o sistémicas fue menor al 1%.&#x0D; Dieciocho pacientes presentaron infecciones fúngicas pulmonares o sistémicas. Ocho padecieron candidemias, cinco criptococosis meningeas, dos histoplasmosis, dos aspergilosis invasoras agudas probables y una aspergilosis pulmonar crónica.&#x0D; La estadía prolongada en terapia intensiva facilitó las fungemias por Candida sp, los casos de histoplasmosis y criptococosis parecen relacionarse con la enfermedad avanzada por VIH y no con COVID-19. Los enfermos con un componente inflamatorio basal alto con neumonía grave por coronavirus se relacionan más con micosis invasoras que los enfermos VIH positivos con niveles bajos de LTCD4+.

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

The Association of Long-term Macrolide Therapy and Nontuberculous Mycobacterial Culture Positivity in Patients With Bronchiectasis

Impact of Advanced HIV Disease on Quality of Life and Mortality in the Era of Combined Antiretroviral Treatment.

Currently, AIDS or severe immunodeficiency remains as a challenge for people with HIV (PWHIV) and healthcare providers. Our purpose was to analyze the impact of advanced HIV disease (AHD) on mortality, life expectancy and health-related quality of life (HRQoL). We reviewed cohort studies and meta-analyses conducted in middle- and high-income countries. To analyze HRQoL, we selected studies that reported overall health and/or physical/mental health scores on a validated HRQoL instrument. AIDS diagnosis supposes a higher risk of mortality during the first six months, remaining higher for 48 months. It has been reported that cancer and cardiovascular disease persist as frequent causes of mortality in PWHIV, especially those with previous or current AHD. PWHIV who initiate combination antiretroviral therapy (cART) with CD4 < 200 cells/µL have significantly lower estimated life expectancy than those with higher counts. AHD is associated with lower HRQoL, and a worse physical health or mental health status. AIDS and non-AIDS defining events are significant predictors of a lower HRQoL, especially physical health status. AHD survivors are in risk of mortality and serious comorbidities, needing special clinical attention and preventive programs for associated comorbidities. Their specific needs should be reflected in HIV guidelines.

A Study of Clearance of Infection in HIV-Associated Cryptococcal Meningitis after Amphotericin-Based Induction and Fluconazole-Based Consolidation Therapy

Abstract Introduction India has third largest human immunodeficiency virus (HIV) population in the world. Average HIV prevalence was 0.22% (range, 0.16–0.30%) in 2017, and Manipur is one of the five states with the highest prevalence of HIV. Cryptococcal meningitis being one of the acquired immunodeficiency syndrome (AIDS)-defining illnesses is the second most common cause of opportunistic neuro-infection and usually occurs in advanced HIV disease when the cluster of differentiation 4 glycoprotein (CD4+) count is usually less than 100 cells/µL. Treatment includes amphotericin-B induction therapy for 2 weeks followed by fluconazole consolidation therapy for 8 weeks as per National AIDS Control Organisation guidelines. There is not much data on how much infection is cleared off after induction and consolidation treatment. So, this study was conducted to know the clearance of Cryptococci in cerebrospinal fluid (CSF) after induction and consolidation treatment in people living with HIV (PLHIV)-associated cryptococcal meningitis. Objective This work aimed to study the persistence of cryptococcal meningitis after amphotericin-based 2 weeks of induction therapy and 8 weeks of consolidation therapy with fluconazole and to evaluate the association between CD4 count and clearance rate of cryptococcal infection. Materials and Methods The study was conducted in Department of Medicine, Regional Institute of Medical Sciences, Imphal, from 2016 to 2018. Fifty-one patients above 18 years of age diagnosed as cryptococcal meningitis with HIV were included and treated with amphotericin for 2 weeks and fluconazole for 10 weeks. CSF analysis was done at 2nd and 10th weeks to study the clearance of infection. Results At 2nd week of induction therapy, out of 51 patients, 28 (54.9%) got cleared of infection, 18 (35.3%) had persistent infection, and 5 (9.2%) patients had either died or discontinued treatment. At 10th week of consolidation therapy, 36 (70.5%) patients got cleared of cryptococcal infection, 2 (4%) patients were having persistent infection, and 5 (9.8%) patients died, while 8 (15.7%) patients were lost in follow-up. However, after excluding mortality and lost in follow-up cases, from analysis in final outcome, 94% (34 out of 36) patients showed response to this regimen. Conclusion The present study showed that cryptococcal meningitis in PLHIV responded to amphotericin-based induction therapy with 60% clearance of infection followed by fluconazole-based consolidation therapy with 94% of clearance of infection. However, there is still need for good antifungal regimen that could clear infection in induction phase with less side effects.

Divergence of Delta and Beta Variants and SARS-CoV-2 Evolved in Advanced HIV Disease into Two Serological Phenotypes

SARS-CoV-2 continues to evolve variants which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the Delta variant has been reported to escape Beta variant infection elicited immunity. Mapping the serological distance between current and emerging variants will likely guide design of vaccines which can target all variants. Here we mapped neutralization of SARSCoV-2 ancestral and Beta and Delta variant viruses by antibodies elicited by each variant in SARS-CoV-2 convalescent individuals. We also serologically characterized and mapped SARS-CoV-2 which evolved from an ancestral strain in prolonged infection in an immunosuppressed individual due to advanced HIV disease. Beta virus showed moderate (7-fold) and Delta virus slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, Delta virus had pronounced escape from Beta elicited immunity (12fold), and Beta virus even stronger escape from Delta immunity (34-fold). Evolved virus had 9-fold escape from ancestral immunity, 27-fold escape from Delta immunity, but was effectively neutralized by Beta immunity. We conclude that Beta and Delta variants are serologically distant, further than each is from ancestral virus. An example of SARS-CoV2 evolved during advanced HIV disease immune suppression is serologically close to Beta and far from Delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes which may become serotypes, and that vaccines tailored to one variant may become vulnerable to infections with another. Funding: This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 (WVV). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 9834). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: None to declare. Ethics Approval Statement: Nasopharyngeal and oropharyngeal swab samples and plasma samples were obtained from hospitalized adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020).

The burden of serious fungal infections in Sierra Leone: a national estimate.

Sierra Leone is a small, resource-limited country that has a low national prevalence of human immunodeficiency virus (HIV) and a very high burden of tuberculosis (TB). Fungal diseases are probably common, but poorly documented. In this article, we reviewed the existing literature on fungal epidemiology in Sierra Leone using national, regional, and international data, identified knowledge gaps, and propose solutions to address the challenges on the prevention and control of fungal diseases in Sierra Leone and similar countries. In advanced HIV disease, we estimate 300 cryptococcal meningitis, 640 Pneumocystis pneumonia, and over 4000 esophageal candidiasis cases annually. Chronic lung disease is common, with an estimated 6000 cases of chronic pulmonary aspergillosis, many mistaken for TB, 5000 adults with allergic bronchopulmonary aspergillosis complicating asthma, and probably over 6600 cases of severe asthma with fungal sensitization. Invasive aspergillosis is estimated at 478 cases. None of these diagnoses are made in Sierra Leone at present. Major burdens are recurrent vulvovaginal candidiasis (85,400) and tinea capitis in children (266,450). Improvement in fungal disease diagnosis in Sierra Leone will enable better estimates to be made and reduce morbidity and mortality.

COVID-19 Disease Severity Among People With HIV Infection or Solid Organ Transplant in the United States: A Nationally-Representative, Multicenter, Observational Cohort Study

Background: Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction.Methods: We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction.Findings: Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm 3 , PWH with CD4Interpretation: Individuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.Funding Information: NCATS U24 TR002306. ALO was supported by CTSA award No. UL1TR002649 from the National Center for Advancing Translational Sciences. Dr. Gregory Kirk is supported in part by NIAID K24AI118591. Dr. Rena C. Patel’s effort was supported by NIAID of the NIH (K23AI120855). Ms. Andersen received doctoral training support from the National Heart, Lung and Blood Institute Pharmacoepidemiology T32 Training Program (T32HL139426). Dr. Todd Brown is supported in part by NIAID K24AI120834.Declaration of Interests: None to declare. Ethics Approval Statement: The N3C Data Enclave is approved under the authority of the NIH Institutional Review Board (IRB, IRB00249128) with Johns Hopkins University School of Medicine as a central IRB for data transfer. Institutional IRB at each study site approved the study protocol or ceded to this single IRB. The current study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.