A Simple Predictive Score to Distinguish between Disseminated Histoplasmosis and Tuberculosis in Patients with HIV

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients.

Advanced HIV Disease Management Practices within Inpatient Medicine Units at a Referral Hospital in Zambia: A Retrospective Chart Review

Background Zambia recently achieved UNAIDS 90-90-90 treatment targets for HIV epidemic control; however, inpatient facilities continue to face a large burden of patients with advanced HIV disease and HIV-related mortality. Management of advanced HIV disease, following guidelines from outpatient settings, may be more difficult within complex inpatient settings. We evaluated adherence to HIV guidelines during hospitalization, including opportunistic infection (OI) screening, treatment, and prophylaxis. Methods We reviewed inpatient medical records of people living with HIV (PLHIV) admitted to the University Teaching Hospital in Lusaka, Zambia between December 1, 20218 and April 30, 2019. We collected data on patient demographics, antiretroviral therapy (ART), HIV biomarkers, and OI screening and treatment – including tuberculosis (TB), Cryptococcus, and OI prophylaxis with cotrimoxazole (CTX). Screening and treatment cascades were constructed based on the 2017 WHO Advanced HIV Guidelines. Results We reviewed files from 200 charts of patients with advanced HIV disease; of these 92% (184/200) had been on ART previously; 58.1% (107/184) for more than 12 months. HIV viral load (VL) testing was uncommon but half of VL results were high. 39% (77/200) of patients had a documented CD4 count result. Of the 172 patients not on anti-TB treatment (ATT) on admission, TB diagnostic tests (either sputum Xpert MTB/RIF MTB/RIF or urine TB-LAM) were requested for 105 (61%) and resulted for 60 of the 105 (57%). Nine of the 14 patients (64%) with a positive lab result for TB died before results were available. Testing for Cryptococcosis was performed predominantly in patients with symptoms of meningitis. Urine TB-LAM testing was rarely performed. Conclusions Inconsistent CD4 testing reduced recognition of advanced HIV and OI screening was suboptimal, in part due to laboratory challenges. HIV programs can potentially reduce mortality and identify PLHIV with retention and adherence issues through strengthening inpatient activities, including VL testing.

Predictors of late presentation and advanced HIV disease among people living with HIV in Oman (2000–2019)

Background The aim of this study was to determine the proportions and predictors of late presentation (LP) and advanced HIV disease (AD) in Oman. LP and AD were defined as presenting with a baseline CD4 count of < 350 and < 200 cells/mm3, respectively. Methods We conducted a retrospective database analysis of the National HIV Surveillance System to identify Omani people (≥ 13 years old) who were diagnosed with HIV in the period between January 2000 and December 2019 and had a documented baseline CD4 cell count. We calculated the rates and trend over time of LP and AD. A logistic regression was carried out to determine the predictors of LP and AD. Results A total of 1418 patients, who were diagnosed with HIV in the period from January 2000 to December 2019, were included; 71% were male and 66% were heterosexuals. The median (IQR) age at diagnosis was 33 (25–39) years. Overall, 71% (95% CI: 68–73) and 46% (95% CI: 44–49) of patients had LP and AD at presentation, respectively. The LP percentage decreased from 76% in 2000–2004 to 69% in 2015–2019; AD percentage decreased from 57 to 46% over the same period. The proportions of men with LP and AD were higher than women (74% vs. 62 and 50% vs. 36%, respectively). The percentages of persons with LP among people aged 13–24, 25–49, and ≥ 50 years were 65, 71, and 84%, respectively. The proportions of persons with AD among people aged 13–24, 25–49, and ≥ 50 years were 39, 46, and 65%, respectively. Logistic regression showed that male sex, older age, having an “unknown” HIV risk factor, and living outside Muscat were independent predictors of AD. Male sex also independently predicted LP. Conclusions This analysis indicates that a significant proportion of new HIV cases in Oman continue to present late. This study identified patient subgroups at greatest risk of late HIV diagnosis such as men and older people. Targeted interventions and greater efforts to scale up HIV testing services in Oman are needed.

Longitudinal analysis of sociodemographic, clinical and therapeutic factors of HIV-infected individuals in Kinshasa at antiretroviral therapy initiation during 2006-2017

Background The benefits of antiretroviral therapy (ART) underpin the recommendations for the early detection of HIV infection and ART initiation. Late initiation (LI) of antiretroviral therapy compromises the benefits of ART both individually and in the community. Indeed, it promotes the transmission of infection and higher HIV-related morbidity and mortality with complicated and costly clinical management. This study aims to analyze the evolutionary trends in the median CD4 count, the median time to initiation of ART, the proportion of patients with advanced HIV disease at the initiation of ART between 2006 and 2017 and their factors. Methods and findings HIV-positive adults (≥ 16 years old) who initiated ART between January 1, 2006 and December 31, 2017 in 25 HIV care facilities in Kinshasa, the capital of DRC, were eligible. The data were processed anonymously. LI is defined as CD4≤350 cells/μl and/or WHO clinical stage III or IV and advanced HIV disease (AHD), as CD4≤200 cells/μl and/or stage WHO clinic IV. Factors associated with advanced HIV disease at ART initiation were analyzed, irrespective of year of enrollment in HIV care, using logistic regression models. A total of 7278 patients (55% admitted after 2013) with an average age of 40.9 years were included. The majority were composed of women (71%), highly educated women (68%) and married or widowed women (61%). The median CD4 was 213 cells/μl, 76.7% of patients had CD4≤350 cells/μl, 46.1% had CD4≤200 cells/μl, and 59% of patients were at WHO clinical stages 3 or 4. Men had a more advanced clinical stage (p <0.046) and immunosuppression (p<0.0007) than women. Overall, 70% of patients started ART late, and 25% had AHD. Between 2006 and 2017, the median CD4 count increased from 190 cells/μl to 331 cells/μl (p<0.0001), and the proportions of patients with LI and AHD decreased from 76% to 47% (p< 0.0001) and from 18.7% to 8.9% (p<0.0001), respectively. The median time to initiation of ART after screening for HIV infection decreased from 40 to zero months (p<0.0001), and the proportion of time to initiation of ART in the month increased from 39 to 93.3% (p<0.0001) in the same period. The probability of LI of ART was higher in married couples (OR: 1.7; 95% CI: 1.3–2.3) (p<0.0007) and lower in patients with higher education (OR: 0.74; 95% CI: 0.64–0.86) (p<0.0001). Conclusion Despite increasingly rapid treatment, the proportions of LI and AHD remain high. New approaches to early detection, the first condition for early ART and a key to ending the HIV epidemic, such as home and work HIV testing, HIV self-testing and screening at the point of service, must be implemented.

Divergence of delta and beta variants and SARS-CoV-2 evolved in prolonged infection into distinct serological phenotypes

SARS-CoV-2 continues to evolve variants of concern (VOC) which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the delta VOC has been reported to escape beta elicited immunity. Systematic mapping of the serological distance of current and emerging variants will likely guide the design of vaccines which can target all variants. Here we isolated and serologically characterized SARS-CoV-2 which evolved from an ancestral strain in a person with advanced HIV disease and delayed SARS-CoV-2 clearance. This virus showed evolving escape from self antibody neutralization immunity and decreased Pfizer BNT162b2 vaccine neutralization sensitivity. We mapped neutralization of evolved virus and ancestral, beta and delta variant viruses by antibodies elicited by each VOC in SARS-CoV-2 convalescent individuals. Beta virus showed moderate (7-fold) and delta slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, delta virus had stronger escape from beta elicited immunity (12-fold), 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 are serologically distant, further than each is from ancestral, and that virus evolved in prolonged infection during advanced HIV disease is serologically close to beta and far from delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes and that vaccines tailored to one variant may become vulnerable to infections with another.

Decrease in late presentation for HIV care in Kinshasa, DRC, 2006–2020

Introduction Late 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). Results A 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. Conclusions The 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.

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. Objectives: The relationship between sociodemographic factors and malnutrition in the background of HIV was evaluated. Methods: A cross-sectional descriptive survey was conducted among under-five HIV positive children in Anambra State, Nigeria. 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 <-2SD), 13.3% (49) wasted (WFH < -2SD), and 27.9% (103) stunted (HFA <-2SD). Males were significantly more stunted than females (p<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 >12 months. 26% (96) were orphans, while 28.6% (106) were cared for by single parents. Being on HAART for >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. 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.