Advanced HIV disease at diagnosis among newly diagnosed people with HIV in rural eastern Uganda: a retrospective cohort study

Effectiveness of COVID-19 primary and booster vaccination in HIV-infected individuals

Despite improved access to antiretroviral therapy (ART) for people with HIV (PWH), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PWH who are ART-experienced. Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa. Using data from IeDEA Southern Africa, we included PWH from South Africa, initiating ART from 2004 to 2017 aged more than 5 years with a CD4+ cell count at ART start and at least one subsequent measure. We defined a gap as no visit for at least 18 months. Five states were defined: 'AHD on ART' (CD4+ cell count <200 cells/μl), 'Clinically Stable on ART' (CD4+ cell count ≥200 or if no CD4+ cell count, viral load <1000 copies/ml), 'Early Gap' (commencing ≤18 months from ART start), 'Late Gap' (commencing >18 months from ART start) and 'Death'. Among 32 452 PWH, men and those aged 15-25 years were more likely to progress to unfavourable states. Later years of ART start were associated with a lower probability of transitioning from AHD to clinically stable, increasing the risk of death following AHD. In stratified analyses, those starting ART with AHD in later years were more likely to re-engage in care with AHD following a gap and to die following AHD on ART. In more recent years, those with AHD on ART were more likely to die, and AHD at re-engagement in care increased. To further reduce HIV-related mortality, efforts to address the challenges facing these more vulnerable patients are needed.

Background:Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization’s (WHO) ‘test-and-treat’ strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD.Methods:We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions.Results:While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care.Conclusions:Despite progress with HIV treatment and prevention, a persistent 20%–30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

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.

China launched "treat-all" in 2016 to make all HIV-positive people eligible for ART regardless of disease stage. Widespread treatment may not eliminate advanced HIV. This study investigated the prevalence, characteristics, risk factors, and clinical outcomes of advanced HIV disease (AHD) in newly diagnosed HIV-positive individuals in China during the "treat-all" period. We performed a retrospective cohort study on newly diagnosed adult ART-naive people with HIV (PWH) in Xi'an from 2016 to 2022. The prevalence of AHD and six-month mortality/loss to follow-up (LTFU) were investigated. Risk variables for AHD and predictors of mortality or LTFU in the cohort were investigated using multivariate logistic and Cox regression, respectively. Of the PWH, 47.5% (2999/6318) had AHD at HIV diagnosis. At enrollment, being ≥50 years (aOR: 1.75, 95% CI: 1.44-2.12, P < 0.001; ≥50 vs 18-29), 30-49 years (aOR: 1.43, 95% CI: 1.24-1.65, P < 0.001; 30-49 vs 18-29), opportunity infections (aOR: 7.43, 95% CI: 5.96-9.35, P < 0.001), severe anemia (aOR: 3.56, 95% CI: 1.81-7.70, P = 0.001) and liver disease (aOR: 3.09, 95% CI: 1.48-7.05, P = 0.004) were independently associated with AHD. Within 6 months of enrollment, 95.6% and 58.3% of those who died or were LTFU had AHD. AHD (aHR: 14.30, 95% CI: 4.42-46.30, P < 0.001), ≥50 years (aHR: 5.39, 95% CI: 2.10-13.82, P < 0.001; ≥50 years vs 18-29 years), those with opportunistic infections (aHR: 2.59, 95% CI: 1.54-4.34, P < 0.001), and severe anemia (aHR: 9.89, 95% CI: 5.19-18.87, P < 0.001) were independent predictors of six-month mortality. Under the "treat-all" policy, Xi'an had a high prevalence of AHD upon HIV diagnosis. AHD predicted 6-month mortality. Urgent implementation of targeted strategies is necessary to minimize AHD.

We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross-sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged ≥ 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000-2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease.

Retreatment TB is a risk factor for multidrug-resistant TB among people with HIV in rural eastern Uganda: A nested case-control study

BackgroundInformation about burden, characteristics, predictors, and outcomes of advanced human immunodeficiency virus disease (AHD) is scarce in rural settings of sub-Saharan Africa. Human immunodeficiency virus (HIV) infections and associated deaths remain high despite specific guidelines issued by the World Health Organization (WHO).MethodsBurden of AHD and 6-month death/loss to follow-up (LTFU) were described among 2498 antiretroviral therapy (ART)–naive nonpregnant people with HIV (PWH) aged >15 years enrolled in the Kilombero Ulanga Antiretroviral Cohort in rural Tanzania between 2013 and 2019. Baseline characteristics associated with AHD and predictors of death/LTFU among those with AHD were analyzed using multivariate logistic and Cox regression, respectively.ResultsOf the PWH, 62.2% had AHD at diagnosis (66.8% before vs 55.7% after national uptake of WHO “test and treat” guidelines in 2016). At baseline, older age, male sex, lower body mass index, elevated aminotransferase aspartate levels, severe anemia, tachycardia, decreased glomerular filtration rate, clinical complaints, impaired functional status, and enrollment into care before 2018 were independently associated with AHD. Among people with AHD, incidence of mortality, and LTFU were 16 and 34 per 100 person-years, respectively. WHO clinical stage 3 or 4, CD4 counts <100 cells/µL, severe anemia, tachypnea, and liver disease were associated with death/LTFU.ConclusionsMore than 50% of PWH enrolled in our cohort after test and treat implementation still had AHD at diagnosis. Increasing HIV testing and uptake and implementation of the WHO-specific guidelines on AHD for prevention, diagnosis, treatment of opportunistic infections, and reducing the risks of LTFU are urgently needed to reduce morbidity and mortality.

The 2022 global outbreak of mpox disproportionally affected people with HIV (PWH). We review the data on the presentation, treatment, and prevention of mpox in PWH. Most PWH with mpox had a mild and self-limiting illness, no different to people without HIV. A higher rate of rectal symptoms has been reported among PWH and those with advanced HIV disease were at higher risk of severe disease, hospitalization, and death. Treatment with antivirals was widely used in hospitalized patients without any randomized control trial data to support its use and without any data specifically in PWH. Use of smallpox vaccines to prevent mpox is safe in PWH regardless of CD4+ cell count. There is limited data on efficacy in those with lower CD4+ cell count and on long-term protective efficacy. PWH should be offered vaccination against mpox in line with national guidelines. PWH should be individually risk-assessed for severe mpox, based on their CD4+ cell count and co-morbidities and ideally recruited into treatment trials to build an evidence base on efficacy. HIV and other sexually transmitted infection testing should be offered to all people diagnosed with mpox.

BackgroundDespite global efforts to improve HIV care, late diagnosis and delayed antiretroviral therapy (ART) initiation continue to pose mortality risks among people living with HIV (PLHIV) with advanced HIV disease (AHD). This study investigated factors associated with mortality among PLHIV with AHD in rural North-Central Uganda from January 2018 to December 2021.MethodsWe retrospectively reviewed electronic medical records from 18 health facilities, collecting data on demographics and clinical characteristics, including baseline CD4 count, ART regimen, BMI, TB status, TPT use, WHO clinical stage, and viral load. AHD was defined as a baseline CD4 < 200 cells/mm³. Cox proportional hazards modeling identified mortality-associated factors, reported as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), using a 5% significance level.ResultsWe analyzed 1161 PLHIV with AHD, contributing 1565.6 person-years. There were 84 deaths (7.2%), yielding a mortality rate of 5.4 per 100 person-years (95% CI: 4.33–6.64). Mortality was significantly associated with age ≥ 50 years (aHR 4.16 [1.77–9.77]), no viral load test (aHR 16.23 [7.44–35.39]), viral load non-suppression (aHR 9.05 [3.37–24.29]), CD4 ≤ 50 (aHR 1.91 [1.08–3.39]), no TB prophylaxis (aHR 3.51 [1.83–6.74]), and WHO stage 3 or 4 (aHR 1.91 [1.12–3.27]).ConclusionDespite advances in HIV programs, the mortality rate among patients with AHD highlights ongoing challenges. Early identification of AHD patients, regular viral load testing, optimizing ART and ensuring adherence, along with promoting tuberculosis preventive therapy, could help reduce mortality, improve patient outcomes, and achieve HIV epidemic control by 2030.

To identify mortality trends and risk factors associated with stillbirths and neonatal deaths 1982-2011. Population-based cross-sectional study based on reported pregnancy history in Iganga-Mayuge Health and Demographic Surveillance Site (HDSS) in Uganda. A pregnancy history survey was conducted among women aged 15-49 years living in the HDSS during May-July 2011 (n = 10 540). Time trends were analysed with cubic splines and linear regression. Potential risk factors were examined with multilevel logistic regression with adjusted odds ratios (AOR) and 95% confidence intervals (CI). 34 073 births from 1982 to 2011 were analysed. The annual rate of decrease was 0.9% for stillbirths and 1.8% for neonatal mortality. Stillbirths were associated with several risk factors: multiple births (AOR 2.57, CI 1.66-3.99), previous adverse outcome (AOR 6.16, CI 4.26-8.88) and grand multiparity among 35- to 49-year-olds (AOR 1.97, CI 1.32-2.89). Neonatal deaths were associated with multiple births (AOR 6.16, CI 4.80-7.92) and advanced maternal age linked with parity of 1-4 (AOR 2.34, CI 1.28-4.25) and grand multiparity (AOR 1.44, CI 1.09-1.90). Education, marital status and household wealth were not associated with the outcomes. The slow decline in mortality rates and easily identifiable risk factors calls for improving quality of care at birth and a rethinking of how to address obstetric risks, potentially a revival of the risk approach in antenatal care.

Burden of advanced HIV disease among antiretroviral therapy-experienced persons with HIV in Italy over the past 20 years.

Antiretroviral therapy (ART) has led to diminishing AIDS-related mortality but a concomitant increase in non-communicable diseases (NCDs) for people with HIV (PWH). Whereas physical activity (PA) has been shown to help prevent NCDs and NCD outcomes in other settings, there are few data on PA and its correlates among PWH in high-endemic settings. We aimed to compare PA by HIV serostatus in rural Uganda. We analysed data from the UGANDAC study, an observational cohort including PWH in ambulatory HIV care in Mbarara, Uganda, and age- and gender-matched people without HIV (PWOH). Our primary outcome of interest was PA, which we assessed using the International Physical Activity Questionnaire and considered as a continuous measure of metabolic equivalents in minutes/week (MET-min/week). Our primary exposure of interest was HIV serostatus. We fit univariable and multivariable linear regression models to estimate the relationship between HIV and PA levels, with and without addition of sociodemographic and clinical correlates of PA (MET-min/week). In secondary analyses, we explored relationships restricted to rural residents, and interactions between gender and serostatus. We enrolled 309 participants, evenly divided by serostatus and gender. The mean age of PWH was 52 [standard deviation (SD) 7.2] and 52.6 (SD 7.3) for PWOH. In general, participants engaged in high levels of PA regardless of serostatus, with 81.2% (251/309) meeting criteria for high PA. However, PWOH reported higher mean levels of PA met-minutes/week than PWH (9,128 vs 7,152, p ≤ 0.001), and a greater proportion of PWOH (88.3%; 136/154) met the criteria for high PA compared to PWH (74.2%; 115/155). In adjusted models, lower levels of PA persisted among PWH (β = -1,734, 95% CI: -2,645, -824, p ≤ 0.001). Results were similar in a sensitivity analysis limited to people living in rural areas. In a rural Ugandan cohort, PWOH had higher levels of PA than PWH. Interventions that encourage PA among PWH may have a role in improving NCD risk profiles among PWH in the region.

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.

Latent tuberculosis infection among adults attending HIV services at an urban tertiary hospital in Malawi.