Intractable Chronic Vulval Ulceration Presenting as Immune Reconstitution Inflammatory Syndrome in a Treatment-Failure Patient: A Case Observation

HIV-1 treatment-failure patients are increasingly being initiated on second-line antiretroviral therapy. The case we describe is of a treatment-failure patient who developed intractable chronic vulval ulceration presenting as immune reconstitution inflammatory syndrome (IRIS), following complete viral suppression with second-line highly active antiretroviral treatment (HAART). To the best of our knowledge, this is the first reported case of intractable vulval ulceration IRIS in an HIV-1 treatment-failure patient

Correction of estimates of retention in care among a cohort of HIV-positive patients in Uganda in the period before starting ART: a sampling-based approach.

OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics

Hazardous alcohol consumption is not associated with CD4+ T-cell count decline among PLHIV in Kampala Uganda: A prospective cohort study.

INTRODUCTION: There is limited data on the effects of alcohol on immunological response among persons living with HIV (PLHIV) in sub-Saharan Africa. We assessed the relationship between hazardous alcohol use and CD4+ T-cell count, among PLHIV in Uganda. METHODS: PLHIV aged ≥ 18 years were enrolled in a cohort study at the Infectious diseases clinic Kampala, Uganda. Alcohol consumption was assessed at enrolment (baseline) and 6 monthly thereafter using the alcohol use disorders identification test (AUDIT). The CD4+ T-cell counts, assessed at baseline and over the next 12 months were compared between alcohol use strata, using linear mixed effects regression. Using longitudinal mediation analysis methods, we estimated the effect of alcohol induced ART non-adherence on CD4+ T-cell count. RESULTS: Of the 1566 participants enrolled, 863(44.1%) were non-alcohol users (AUDIT score = 0), 433(27.7%) were non-hazardous (AUDIT score 1-7) alcohol users while 270 (17.2%) were hazardous (AUDIT score ≥ 8) alcohol users. The overall median (IQR) baseline CD4+ T-cell count was 356 (243-516) cells/μl. There were no differences in the median baseline CD4+ T-cell count between hazardous and non-hazardous alcohol users compared to non-alcohol users in both the non-ART (p = 0.43) and ART group (p = 0.77). The mean CD4+ T-cell count over 12 months was not different between hazardous alcohol users and non-alcohol users (non-ART group p = 0.88 and ART group p = 0.62), nor between non-hazardous alcohol users and non-alcohol users (and non-ART group p = 0.66 and ART group p = 0.20). Alcohol use was not associated with a significant natural direct effect on CD4+ T-cell count (1.37 95%CI [-1.78, 4.52] cells/μl, p = 0.39) but had a statistically significant natural indirect effect on reduction of CD4+ T-cell count (-0.91 cells/μl [-1.36, -0.45], p < 0.001) mediated through ART non-adherence. CONCLUSION: Hazardous alcohol use among PLHIV was not directly associated with lower CD4+ T-cell count but had a significant natural indirect effect on CD4+ T-cell count mediated through ART non-adherence. Among PLHIV with lower than expected CD4+ T-cell count, alcohol consumption should be excluded as an underlying factor for non-adherence to ART and any interventions targeting alcohol use should tackle possible ART non-adherence

Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda.

PURPOSE: Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. PARTICIPANTS: A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. FINDINGS TO DATE: Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. FUTURE PLANS: Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug-drug interactions between ART and common drugs used for non-communicable diseases

Antiretroviral Treatment-Associated Tuberculosis in a Prospective Cohort of HIV-Infected Patients Starting ART

Commencement of antiretroviral treatment (ART) in severely immunosuppressed HIV-infected persons is associated with unmasking of subclinical disease. The subset of patients that are diagnosed with tuberculosis (TB) disease while on ART have been classified as ART-associated TB. Few studies have reported the incidence of ART-associated TB and unmasking TB-IRIS according to the International Network for the Study of HIV-Associated IRIS (INSHI) consensus definition. To determine the incidence and predictors of ART-associated TB, we screened 219 patients commencing ART at the Infectious Diseases Clinic in Kampala, Uganda for TB by symptoms, sputum microscopy, and chest X-rays and followed them for one year. Fourteen (6.4%) patients were diagnosed with TB during followup. Eight (3.8%) patients had ART-associated TB (incidence rate of 4.3 per 100 person years); of these, three patients fulfilled INSHI criteria for unmasking TB-associated IRIS (incidence rate of 1.6 per 100 person years). A body mass index of less than 18.5 kg/m2 BMI (HR 5.85 95% CI 1.24–27.46, P = .025) and a C-reactive protein greater than 5 mg/L (HR 8.23 95% CI 1.36–38.33, P = .020) were risk factors for ART-associated TB at multivariate analysis. In conclusion, with systematic TB screening (including culture and chest X-ray), the incidence of ART-associated TB is relatively low in settings with high HIV and TB prevalence

Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis.

BACKGROUND: The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda. METHODS: We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics. RESULTS: 10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24. CONCLUSION: These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis. TRIAL REGISTRATION: The SOUTH trial was registered prospectively. ClinicalTrials.gov Identifier: NCT01782950 ; Registration date: 4th February 2013; Last verified: 13th April 2015

Comparison of different cardiovascular risk tools used in HIV patient cohorts in sub-Saharan Africa; do we need to include laboratory tests?

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death globally, representing 31% of all global deaths. HIV and long term anti-retroviral therapy (ART) are risk factors for development of CVD in populations of people living with HIV (PLHIV). CVD risk assessment tools are currently being applied to SSA populations, but there are questions about accuracy as well as implementation challenges of these tools in lower resource setting populations. We aimed to assess the level of agreement between the various cardiovascular screening tools (Data collection on Adverse effects of anti-HIV Drugs (D:A:D), Framingham risk score, WHO risk score and The Atherosclerotic Cardiovascular Disease Score) when applied to an HIV ART experienced population in Sub-Saharan Africa. METHODS: This study was undertaken in an Anti-Retroviral Long Term (ALT) Cohort of 1000 PLHIV in care who have been on ART for at least 10 years in urban Uganda. A systematic review was undertaken to find the most frequently used screening tools from SSA PLHIV populations; these were applied to the ALT cohort. Levels of agreement between the resulting scores (those including lipids and non-lipids based, as well as HIV-specific and non-HIV specific) as applied to our cohort were compared. Prevalence Bias Adjusted Kappa was used to evaluate agreement between tools. RESULTS: Overall, PLHIV in ALT cohort had a median score of 1.1-1.4% risk of a CVD event over 5 years and 1.7-2.5% risk of a CVD event over 10 years. There was no statistical difference in the risk scores obtained for this population when comparing the different tools, including comparisons of those with lipids and non-lipids, and HIV specific vs non-HIV specific. CONCLUSION: The various tools yielded similar results, but those not including lipids are more feasible to apply in our setting. Long-term cohorts of PLHIV in SSA should in future provide longitudinal data to evaluate existing CVD risk prediction tools for these populations. Inclusion of HIV and ART history factors to existing scoring systems may improve accuracy without adding the expense and technical difficulty of lipid testing

A prospective ascertainment of cancer incidence in sub-Saharan Africa: The case of Kaposi sarcoma.

In resource-limited areas, such as sub-Saharan Africa, problems in accurate cancer case ascertainment and enumeration of the at-risk population make it difficult to estimate cancer incidence. We took advantage of a large well-enumerated healthcare system to estimate the incidence of Kaposi sarcoma (KS), a cancer which has become prominent in the HIV era and whose incidence may be changing with the rollout of antiretroviral therapy (ART). To achieve this, we evaluated HIV-infected adults receiving care between 2007 and 2012 at any of three medical centers in Kenya and Uganda that participate in the East Africa International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortium. Through IeDEA, clinicians received training in KS recognition and biopsy equipment. We found that the overall prevalence of KS among 102,945 HIV-infected adults upon clinic enrollment was 1.4%; it declined over time at the largest site. Among 140,552 patients followed for 319,632 person-years, the age-standardized incidence rate was 334/100,000 person-years (95% CI: 314-354/100,000 person-years). Incidence decreased over time and was lower in women, persons on ART, and those with higher CD4 counts. The incidence rate among patients on ART with a CD4 count &gt;350&nbsp;cells/mm(3) was 32/100,000 person-years (95% CI: 14-70/100,000 person-years). Despite reductions over time coincident with the expansion of ART, KS incidence among HIV-infected adults in East Africa equals or exceeds the most common cancers in resource-replete settings. In resource-limited settings, strategic efforts to improve cancer diagnosis in combination with already well-enumerated at-risk denominators can make healthcare systems attractive platforms for estimating cancer incidence

Ensuring access to safe and nutritious food for all through the transformation of food systems

Action Track 1 of the Food Systems Summit offers an opportunity to bring together the crucial elements of food safety, nutrition, poverty and inequalities in the framework of food systems within the context of climate and environmental change to ensure that all people have access to a safe and nutritious diet. Achieving Action Track 1’s goal is essential to achieving the goals of the other Action Tracks. With less than a decade left to achieve the Sustainable Development Goals (SDGs), most countries are not on a course to hit either the World Health Organisation’s nutrition targets or the SDG 2 targets. The COVID-19 pandemic has exacerbated malnutrition and highlighted the need for food safety. The pandemic has also exposed the deep inequalities in both food systems and societies as a whole. Nonetheless, future food systems can address many of these failings and ensure safe and nutritious food for all. However, structural change is necessary to address the socio-economic drivers behind malnutrition, inequalities and the climate and environmental impacts of food. Adopting a whole-system approach in policy, research and monitoring and evaluation is crucial for managing trade-off and externalities from farm-level to national scales and across multiple sectors and agencies. Supply chain failures will need to be overcome and technology solutions adopted and adapted to specific contexts. A transformation of food systems requires coordinating changes in supply and demand in differentiated ways across world regions: bridging yield gaps and improving livestock feed conversion, largely through agro-ecological practices, deploying soil carbon sequestration and greenhouse gas mitigation at scale, and reducing food loss and waste, as well as addressing over-nourishment and shifting the diets of wealthy populations. The sustainability of global food systems also requires halting the expansion of agriculture into fragile ecosystems, while restoring degraded forests, fisheries, rangelands, peatlands and wetlands. Shifting to more sustainable consumption and production patterns within planetary boundaries will require efforts to influence food demand and diets, diversify food systems, and develop careful land-use planning and management. Integrative policies need to ensure that food prices reflect real costs (including major externalities caused by climate change, land degradation and biodiversity loss, and the public health impacts of malnutrition), reduce food waste and, at the same time, ensure the affordability of safe and healthy food and decent incomes and wages for farmers and food system workers. The harnessing of science and technology solutions and the sharing of actionable knowledge with all players in the food system offer many opportunities. Greater coordination of food system stakeholders is crucial for greater inclusion, greater transparency and more accountability. Sharing lessons and experiences will foster adaptive learning and responsive actions. Careful consideration of the trade-offs, externalities and costs of not acting is needed to ensure that the changes we make benefit all, and especially the most vulnerable in society.https://link.springer.com/book/10.1007/978-3-031-15703-5hj2024Agricultural Economics, Extension and Rural DevelopmentSDG-02:Zero Hunge