Serum E-selectin and endothelial cell-specific Molecule-1 levels among people living with HIV on long term ART in Uganda: a pilot cross-sectional study.

BACKGROUND: Prolonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population. METHODS: This was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin. RESULTS: Of the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 µm/L ranging from 8.44 µm/L and 1,979.36 µm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 µm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 - 149.95, p < 0.05). CONCLUSIONS: The majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.

An observational study in an urban Ugandan clinic comparing virological outcomes of patients switched from first-line antiretroviral regimens to second-line regimens containing ritonavir-boosted atazanavir or ritonavir-boosted lopinavir.

BACKGROUND: The World Health Organisation approved boosted atazanavir as a preferred second line protease inhibitor in 2010. This is as an alternative to the current boosted lopinavir. Atazanavir has a lower genetic barrier than lopinavir. We compared the virological outcomes of patients during the roll out of routine viral load monitoring, who had switched to boosted second- line regimens of either atazanavir or lopinavir. METHODS: This was a cross-sectional study involving adult patients at the Infectious Diseases Institute Kampala, Uganda started on a standard WHO recommended second-line regimen containing either boosted atazanavir or boosted lopinavir between 1 Dec 2014 and 31 July 2015.. Mantel -Haenszel chi square was used to test for the statistical significance of the odds of being suppressed (VL < 400 copies/ml) when on boosted atazanavir compared to boosted lopinavir after stratifying by duration on antiretroviral therapy (ART). Multivariate logistic regression analysis used to determine if the type of boosted protease inhibitor (bPI) was associated with virological outcome. RESULTS: Ninety (90) % on ATV/r and 83% on LPV/r had a VL less than 1000 copies/ml. The odds of being suppressed using the same viral load cut-off while on boosted atazanavir compared to boosted lopinavir was not statistically significant after stratifying for duration on ART (p = 0.09). In a multivariate analysis the type of bPI used was not a predictor of virological outcome (p = 0.60). CONCLUSIONS: Patients using the WHO recommended second-line of boosted atazanavir have comparable virological suppression to those on boosted lopinavir.

Clinical Evaluation of 2 Point-of-Care Lateral Flow Tests for the Diagnosis of Syphilis.

A diagnostic performance study comparing the only Food and Drug Administration-approved, point-of-care (POC) treponemal test (Syphilis Health Check) and the World Health Organization pre-qualified SD Bioline POC treponemal test against a treponemal hemagglutination test (TPHA) and a sequential algorithm of nontreponemal rapid plasma reagin and TPHA found both POC tests had >85% sensitivity compared with the TPHA and >85% sensitivity and >95% specificity compared with the rapid plasma reagin and TPHA standards.

Quantifying retention during pre-antiretroviral treatment in a large urban clinic in Uganda.

BACKGROUND: Retention studies are usually focused on patients on antiretroviral treatment (ART), however in Sub-Saharan Africa many patients get lost to program (LTP) in the pre-ART care period.. We investigated the proportion of patients not retained in care and factors associated with LTP (dead or lost to follow up ≥6 months) in the pre-ART care period. METHODS: We analyzed data from the Infectious Diseases Institute, Kampala, Uganda. We included all adult patients ≥18 years, ART naïve at program enrollment from 1(st)/Jan/2005. We described the number of patients not retained in care during the 3 steps of enrollment-to-treatment "cascade": Step 1) From enrollment to CD4 count testing, Step 2) ART eligibility assessment. Patients were initially considered eligible if CD4 count was <200 cell/µL, and <350 cell/µL from 2012 onwards; Step 3) From eligibility to ART start. We described cumulative probability of being LTP by gender and ART eligibility using Kaplan Meier estimates. We used a Cox proportional hazards model to identify factors associated with being LTP at any stage for all patients and for those with a CD4 count available. Factors considered were age, gender, year of enrollment, and WHO stage. RESULTS AND DISCUSSION: After enrollment in our program, cumulatively, a low proportion of patients (30.8 %) were retained and started on ART. The cumulative probability of being LTP was higher in males and patients not eligible for ART. In the multivariable Cox proportional Hazards model, male gender (HR: 1.19 CI 1.12-1.19) and clinical WHO stage 3 and 4 (HR: 1.20 CI 1.13-1.27) were associated with being LTP while older age was protective (HR: 0.98 0.96-0.99). Patients enrolled in the program more recently were also at lower risk of being LTP. In addition, among patients with CD4 count test, patients with higher CD4 count were at higher risk of being LTP. CONCLUSIONS: In our program there has been suboptimal retention of patients in pre-ART care, particularly of patients not eligible for ART. Since the proportion of eligible patients has recently increased due to the higher recommended threshold for ART eligibility (CD4 count > 500 cell/µL in 2014), this could lead to an increase in program retention as more people fall under the recommended threshold and seek care.

Integration of antenatal syphilis screening in an urban HIV clinic: a feasibility study.

BACKGROUND: Syphilis infection during pregnancy leads to avoidable morbidity and mortality and remains a significant problem in sub-Saharan Africa. Despite global initiatives to increase the proportion of pregnant women screened, implementation has been slow. We sought to investigate the feasibility of adding syphilis screening within an integrated antenatal HIV clinic. METHODS: Pregnant women attending the HIV antenatal clinic were sequentially enrolled and consenting participants answered a questionnaire on sexual behavior and previous pregnancies, provided sociodemographic data, and were tested using rapid plasmin reagin (RPR). If positive, participants were treated with benzathine penicillin. All were given a partner notification slip and were followed up after delivery to determine birth outcomes. RESULTS: 584 of 606 (95.7%) women approached and consented to test for syphilis. 570 women were enrolled (median age 29 (IQR 25-32) with a median (IQR) CD4 of 372 (257-569) cells/µL). Of the 5.1% (29/570) with a positive RPR, all were asymptomatic, were successfully contacted, and treated with benzathine penicillin without adverse reactions. Overall, 61 (12.1%) of the participants had an adverse birth outcome. In the bivariate analysis, only age was significantly different between those with and without a positive RPR (RR = 1.15, 95% CI 1.065-1.248; p < 0.001). Partners of only 10 (34.5%) participants returned for treatment. CONCLUSIONS: Structural interventions such as opt-out testing for syphilis within integrated HIV-antenatal care clinics are feasible and capitalize on the excellent care programs that have already been established for HIV care. Novel approaches are required for partner notification.

Longitudinal patients' cohorts for impactful research and HIV care at the Infectious Diseases Institute.

Introduction: Observational studies provide important evidence supporting the feasibility and effectiveness of health interventions. The 20-year-old Infectious Diseases Institute (IDI) established to respond to infectious diseases, specifically HIV/AIDS, invested in the set-up of longitudinal cohorts. In this paper we discuss the results of these cohorts and their impact on the response to the HIV pandemic in Uganda. Methods: IDI invested in experienced system developers, clinic and laboratory capacity to create the infrastructure to host longitudinal cohorts. Several cohorts were created, including patients initiated and followed up on ART, specialized cohorts (e.g. TB co-infection) and long-term cohorts with patients on ART for over 10 years and aged 60 and above. These cohorts function as platforms for sub-studies, attracting collaborators and students. Results: Data from the IDI cohorts contributed evidence to ART programs on when to start, which drugs to use, how to best monitor and which models of care to implement. Sub-studies contributed to management of opportunistic infections, understanding immunological response and the emerging complications of non-communicable diseases. Conclusion: Cohorts provide a platform for clinical care, training, and research to inform strategic responses and put Makerere University at the center of the response to the HIV pandemic in the region.

Intrapreneurship and technological innovation in optimizing qualitative research as evidenced at Infectious Diseases Institute, Uganda.

BACKGROUND: Discrepancies between what is transcribed and the actual interview recordings were noticed in qualitative research reports. This study aimed at the development of a new transcription software (Jiegnote), and the evaluation of its effectiveness in the optimization of the transcription process, to minimize transcription completion time, and errors in qualitative research. METHODS: The study was a mixed methods project implemented from September to November 2020. The qualitative aspect of the study was phenomenological in perspective whereas the quantitative consisted of a randomized controlled trial (RCT) with a parallel design. RESULTS: At the time of the study, the Jiegnote software was a working prototype. We enrolled a total of 26 participants; 14 participants had their data analyzed in the RCT part of the study, 13 participated in the in-depth interviews, and 22 in the answering of Semi Structured Questionnaires. Upon the execution of an independent t test, results showed that, there was no statistical significance between the intervention and control means. On considering the total average transcription completion time and the type of language in which an audio case was recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.413438) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda), and a large impact (Hedges' g = 1.190919) in reducing the total average time taken to transcribe audio cases that were recorded in a foreign language (English). On considering the total average number of transcription errors and the type of language in which an audio case is recorded, the effect size evaluation implied that the Jiegnote software had a small impact (Hedges' g = 0.213258) in reducing the total average time taken to translate and transcribe audio cases that were recorded in a local language (Luganda). This was further observed (Hedges' g = 0.039928) in the transcription of cases that were recorded in a foreign language (English). On considering the in-depth interview data outcomes, participants responded that the Jiegnote software media looping functions (algorithm) enabled them to accomplish their transcription tasks in a shorter time and with fewer errors compared to the traditional methods. CONCLUSION: The study demonstrates utilities associated with intrapreneurship and technological innovation in an organization setting whereby, the Jiegnote technology that was developed by the researchers, had some impact on the optimization of the qualitative research value chain. This was observed through the effect size (impact) evaluations that were conducted to investigate the superiority of the Jiegnote software against the traditional transcription methods, in minimizing the average number of errors committed, and time taken to complete a transcription process.

Uptake of hepatitis B-HIV co-infection screening and management in a resource limited setting.

BACKGROUND: WHO hepatitis B guidelines recommend testing all new HIV patients, treating them accordingly or providing immunization. At the Infectious Diseases Institute (IDI) following an audit done in 2012, only 46% patients had been screened for hepatitis B with variable management plans therefore new internal guidelines were implemented. This study describes the uptake of hepatitis B screening and management of patients with hepatitis B and HIV con-infection after the implementation. METHODS: Data included for all HIV positive patients in care at IDI by October 2015. Data are expressed as median with interquartile range (IQR) and percentages were compared using the chi square test. Statistical analysis was performed using STATA version 13. The IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) was 40 IU/ml. RESULTS: Number of hepatitis B screening tests increased from 800 by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis B positives were switched to a tenofovir (TDF) containing regimen. CONCLUSION: Our study confirms the importance of screening for hepatitis B and of using ART regimens containing tenofovir in hepatitis B co-infected patients. Whilst our program has made improvements in care still 18.6% of patients with hepatitis B were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done. Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up.

Describing Point of Entry into Care and Being Lost to Program in a Cohort of HIV Positive Pregnant Women in a Large Urban Centre in Uganda.

Introduction. We aim to describe the time of entry into care and factors associated with being lost to program (LTP) in pregnant women on Option B Plus in an integrated HIV and antenatal care (ANC) clinic in Uganda. Methods. We included all pregnant women enrolled into the integrated HIV-ANC clinic from January 2012 to 31st July 2014, while the follow up period extended up to October 30th 2015. LTP was defined as being out of care for ≥3 months. Results. Overall 856 women were included. Only 36.4% (86/236) of the women were enrolled in the first trimester. Overall 69 (8.1%) were LTP. In the multivariate analysis older women (HR: 0.80 per five-year increase, CI: 0.64-1.0, and P = 0.060) and women on ART at the time of pregnancy (0.58, CI: 0.34-0.98, and P = 0.040) were more likely not to be LTP. Among women already on ART at the time of pregnancy no factor was associated with LTP. Conclusion. Our results suggest the need for interventions to enhance prompt linkage of HIV positive women to HIV services for ART initiation and for increased retention particularly in young and ART naive women.