Predictors of oral pre-exposure prophylaxis (PrEP) uptake among individuals in a HIV vaccine preparedness cohort in Masaka, Uganda

Oral pre-exposure prophylaxis (PrEP) significantly reduces human immunodeficiency virus (HIV) acquisition risk. However, data on predictors of PrEP uptake in sub-Saharan Africa are limited. We assessed predictors of PrEP uptake among HIV-uninfected high risk individuals enrolled in a HIV vaccine preparedness study in Masaka, Uganda.Between July 2018 and October 2020, we recruited adults (18-40 years) from sex work hotspots along the trans-African highway and Lake Victoria fishing communities. We collected baseline data on socio-demographics and PrEP awareness, and provided HIV counselling and testing, information on PrEP, and PrEP referrals at quarterly visits. Urine pregnancy tests (women) and data collection on sexual risk behaviour and PrEP uptake were performed every 6 months. We analysed PrEP uptake among participants who had completed 6 months of follow-up.Of the 588 cohort participants, 362 (62%) were included in this analysis. Of these, 176 (49%) were female, 181 (50%) were aged ≤24 years, 104 (29%) worked in sex work hotspots, 74 (20%) were fisher folk. Only 75 (21%) participants initiated PrEP. Predictors of PrEP uptake included having ≥6 sex partners (adjusted odds ratio [aOR] = 2.29; 95% confidence interval [CI] 1.26-4.17), engaging in transactional sex (aOR = 2.23; 95% CI 0.95-5.20), and residence in a nonfishing community (aOR = 2.40; 95% CI 1.14-5.08). The commonest reasons for not starting PrEP were pill burden (38%) and needing more time to decide (27%).PrEP uptake was low and associated with HIV risk indicators in this cohort. Interventions are needed to improve access to PrEP especially in fishing communities

Quality of life and associated factors among HIV positive patients after completion of treatment for Cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CCM) remains one of the leading causes of mortality among HIV infected patients. Due to factors such as the severity of CCM pathology, the quality of life (QOL) of patients post-treatment is likely to be poor. Few studies have reported on QOL of CCM patients post treatment completion. We used data collected among patients in the CryptoDex trial (ISRCTN59144167) to determine QOL and associated factors at week 10 and six months from treatment initiation. METHODOLOGY: CryptoDex was a double-blind placebo-controlled trial of adjunctive dexamethasone in HIV infected adults with CCM, conducted between 2013 and 2015 in six countries in Asia and Africa. QOL was determined using the descriptive and Visual Analog Scales (VAS) of the EuroQol Five-Dimension-Three-Level (EQ-5D-3L) tool. We derived index scores, and described these and the VAS scores at 10 weeks and 6 months; and used linear regression to determine the relationship between various characteristics and VAS scores at both time points. VAS scores were interpreted as very good (81-100), good (51-80), normal (31-50) and bad/very bad (0-30). RESULTS: Of 451 patients enrolled in the trial, 238 had QOL evaluations at week 10. At baseline, their mean age (SD) was 35.2(8.5) years. The mean index scores (SD) were 0.785(0.2) and 0.619(0.4) among African and Asian patients respectively at week 10, and 0.879(0.2) and 0.731(0.4) among African and Asian patients respectively at month six. The overall mean VAS score (SD) at 10 weeks was 57.2 (29.7), increasing significantly to 72(27.4) at month six (p<0.001). At week 10, higher VAS score was associated with greater weight (p = 0.007) and being African (p<0.001), while lower VAS score was associated with positive yeast culture at day 14 (p = 0.026). At month six, higher VAS score remained associated with African origin (p = 0.006) while lower VAS score was associated with positive yeast culture (p = 0.006). Lower VAS scores were associated with higher number of inpatient days at 10 weeks and 6 months (p = 0.003 and 0.002 respectively). CONCLUSION: QOL was good among patients that had completed therapy for CCM, but below perfect. Strategies to improve QOL among CCM survivors are required

Determinants of two-year mortality among HIV positive patients with Cryptococcal meningitis initiating standard antifungal treatment with or without adjunctive dexamethasone in Uganda.

Globally, early initiation of antiretroviral therapy for HIV led to a reduction in the estimated mortality from cryptococcal meningitis (CCM) from 624,700 in 2009 to 181,100 in 2014. However, CCM remains one of the leading causes of mortality among HIV infected patients especially in sub-Saharan Africa where 75% of the deaths occur. Most of the studies evaluating mortality have reported short-term mortality (at or before 10 weeks of therapy). We determined mortality and associated factors among patients treated for CCM in the CryptoDex trial (ISRCTN59144167) in Uganda, and the effect of dexamethasone adjunctive therapy on mortality at two years. We conducted a retrospective cohort study between May 2017 and July 2017 to determine the long term survival (up to 2 years post-randomization) of all patients who had been enrolled into the CryptoDex trial in Uganda. The CryptoDex trial recruited between April 2013 and February 2015. We estimated mortality rates and determined factors affecting mortality at two years using Cox regression. The study followed up 211 participants, 127 (60.2%) of whom were male. Sixteen participants (7.58%) were diagnosed with HIV at the same admission when CCM was diagnosed. By two years following randomization 127 (60%) participants had died, a mortality rate of 67 deaths per 100 person-years. Mortality was associated with Glasgow coma score (GCS) below 15 (adjusted Hazard ratio (aHR) 1.77, 95% CI: 1.02-2.44), p = 0.040; weight (aHR 0.97, per 1 Kg increase; 95% CI: 0.94-0.99), p = 0.003; and presence of convulsions (aHR 2.31, 95% CI: 1.32-4.04), p = 0.004, while dexamethasone use and fungal burden had no effect. Long-term mortality in CCM patients remains high even among patients receiving recommended therapy. Strategies to improve long-term survival in CCM patients are urgently needed, especially targeting those with reduced GCS, low weight, and convulsions

Implementation of accelerated research: strategies for implementation as applied in a phase 1 Ad26.ZEBOV, MVA-BN-Filo two-dose Ebola vaccine clinical trial in Uganda.

BACKGROUND: The 2013-2016 Ebola epidemic in West Africa is the worst ever caused by Ebolaviruses with over 28,000 human cases and 11,325 deaths. The World Health Organisation (WHO) declared the epidemic a public health crisis that required accelerated development of novel interventions including vaccines. The Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit (MRC/UVRI & LSHTM Uganda Research Unit) was among the African research sites that implemented the VAC52150EBL1004 Ebola vaccine trial. OBJECTIVE: We report on the strategies utilised by the Unit and sponsor in ensuring expedited clinical trial approval and accelerated conduct. METHODS: Janssen Vaccines and Prevention B.V. conducted a phase 1 trial to evaluate the safety, tolerability, and immunogenicity of heterologous two-dose vaccination regimens using Ad26.ZEBOV and MVA-BN-Filo, in healthy adults in Africa. Accelerated implementation strategies are hereby presented. RESULTS: Strategies included: holding the African Vaccine Regulatory Forum (AVAREF) joint review meeting; expedited review by institutional ethics and country-specific regulatory bodies; competitive recruitment between sites; electronic data capture (EDC); frequent study monitoring schedule; involvement of a community advisory board (CAB); and utilization of a 'phased' study information-sharing approach in community engagement and participant recruitment. These strategies enabled the site to acquire approvals within 2 months and enrol 47 participants within a spurn of five. The same milestone is usually acquired in at least 1 year without accelerated implementation. CONCLUSION: The use of well-thought strategies by sponsors and research sites can enable the implementation of accelerated research. We recommend the use of similar strategies in other settings

COVID-19 Vaccine Acceptability Among Healthcare Facility Workers in Sierra Leone, the Democratic Republic of Congo and Uganda: A Multi-Centre Cross-Sectional Survey.

Objectives: This cross-sectional survey explored COVID-19 vaccine acceptability among public healthcare facility workers in Kambia (Sierra Leone), Goma (Democratic Republic of Congo) and Masaka (Uganda). Methods: Questionnaire-based interviews conducted between April-October 2021 explored participants' knowledge and perceptions of, and attitudes towards, the COVID-19 pandemic and COVID-19 vaccines, as well as COVID-19 vaccine acceptability (defined as uptake of ≥1 dose or intent to get vaccinated). Results: Whilst most (n = 444; 81.8%) of the 543 participants had one or more concerns about COVID-19 vaccines, 487 (89.7%) nonetheless perceived that they were important for pandemic control. Most participants from Kambia or Masaka either were vaccinated (n = 137/355; 38.6%) or intended to get vaccinated (n = 211/355; 59.4%) against COVID-19. In Goma, all 188 participants were unvaccinated; only 81 (43.1%) participants intended to get vaccinated, and this was associated with positive perceptions about COVID-19 vaccines. In Goma, the most common reasons for not wanting a COVID-19 vaccine were concerns that the vaccines were new (n = 75/107; 70.1%) and fear of side effects (n = 74/107; 69.2%). Conclusion: Reported COVID-19 vaccine acceptability was high among healthcare facility workers in Kambia and Masaka. The lower vaccine acceptability in Goma may highlight the importance of social mobilisation and accurate, accessible information that addresses specific concerns

Knowledge, Attitudes, and Practices Regarding COVID-19 among Healthcare Workers in Uganda: A Cross-Sectional Survey.

Healthcare workers (HCWs) are at high risk of COVID-19. However, data on HCWs' knowledge, attitudes, and practices (KAP) toward COVID-19 are limited. Between September and November 2020, we conducted a questionnaire-based COVID-19 KAP survey among HCWs at three hospitals in Uganda. We used Bloom's cut-off of ≥80% to determine sufficient knowledge, good attitude, and good practice, and multivariate Poisson regression with robust variance for statistical analysis. Of 717 HCWs invited to participate, 657 (91.6%) agreed and were enrolled. The mean age (standard deviation) of enrollees was 33.2 (10.2) years; most were clinical HCWs (64.7%) and had advanced secondary school/other higher-level education (57.8%). Overall, 83.9% had sufficient knowledge, 78.4% had a positive attitude, and 37.0% had good practices toward COVID-19. Factors associated with KAP were: Knowledge: being a clinical HCW (aRR: 1.12; 95% CI: 1.02-1.23) and previous participation in health research (aRR: 1.10; 95% CI: 1.04-1.17); Attitude: age > 35 years (aRR: 0.88; 95% CI: 0.79-0.98); Practice: being a clinical HCW (aRR: 1.91; 95% CI: 1.41-2.59). HCWs in Uganda have good knowledge and positive attitude but poor practices towards COVID-19. Differences in COVID-19 KAP between clinical and non-clinical HCWs could affect uptake of COVID-19 interventions including vaccination

Antiretroviral initiation at ≥800 CD4+ cells/ mm 3 associated with lower HIV reservoir size.

BACKGROUND: Identifying factors that determine the frequency of latently infected CD4+ T-cells on antiretroviral therapy (ART) may inform strategies for HIV cure. We investigated the role of CD4 count at ART initiation for HIV persistence on ART. METHODS: Among participants of the Strategic Timing of Antiretroviral Treatment (START) Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500-599, 600-799 or ≥800 cells/mm 3. After 36-44 months on ART, we quantified levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA) and 2-long terminal repeat HIV-DNA in CD4+ T-cells and measured plasma HIV-RNA by single-copy assay. We measured T-cell expression of HLA-DR, programmed death-1, phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. RESULTS: We enrolled 146 PWH, 36 in the 500-599, 60 in the 600-799 and 50 in the ≥800 CD4 strata. After 36-44 months of ART, total HIV-DNA, plasma HIV-RNA and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥800 cells/mm 3 at ART initiation compared to 600-799 or 500-599 cells/mm 3. The median level of HIV-DNA after 36-44 months of ART was lower by 75% in participants initiating ART with ≥800 vs. 500-599 cells/mm 3 [median (IQR): 16.3 (7.0-117.6) vs. 68.4 (13.7-213.1) copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females.. CONCLUSION: Initiating ART with a CD4+ count ≥800 cells/mm 3 compared to 600-799 or 500-599 cells/mm 3 was associated with achieving a substantially smaller HIV reservoir on ART

Determinants of loss to follow-up among HIV positive patients receiving antiretroviral therapy in a test and treat setting: A retrospective cohort study in Masaka, Uganda.

BACKGROUND:Retaining patients starting antiretroviral therapy (ART) and ensuring good adherence remain cornerstone of long-term viral suppression. In this era of test and treat (T&T) policy, ensuring that patients starting ART remain connected to HIV clinics is key to achieve the UNAIDS 90-90-90 targets. Currently, limited studies have evaluated the effect of early ART initiation on loss to follow up in a routine health care delivery setting. We studied the cumulative incidence, incidence rate of loss to follow up (LTFU), and factors associated with LTFU in a primary healthcare clinic that has practiced T&T since 2012. METHODS:We retrospectively analyzed extracted routine program data on patients who started ART from January 2012 to 4th July 2016. We defined LTFU as failure of a patient to return to the HIV clinic for at least 90 days from the date of their last appointment. We calculated cumulative incidence, incidence rate and fitted a multivariable Cox proportion hazards regression model to determine factors associated with LTFU. RESULTS:Of the 7,553 patients included in our sample, 3,231 (42.8%) started ART within seven days following HIV diagnosis. There were 1,180 cases of LTFU observed over 15,807.7 person years at risk. The overall incidence rate (IR) of LTFU was 7.5 (95% CI, 7.1-7.9) per 100 person years of observation (pyo). Cumulative incidence of LTFU increased with duration of follow up from 8.9% (95% CI, 8.2-9.6%) at 6 months to 20.2% (95% CI, 19.0-21.4%) at 48 months. Predictors of elevated risk of LTFU were: starting ART within 7 days following HIV diagnosis ((aHR) = 1.69, 95% CI, 1.50-1.91), lack of a telephone set (aHR = 1.52, 95% CI, 1.35-1.71), CD4 cell count of 200-350μ/ml (aHR = 1.21, 95% CI, 1.01-1.45) and baseline WHO clinical stage 3 or 4 (aHR = 1.35, 95% CI, 1.10-1.65). Factors associated with a reduced risk of LTFU were: baseline age ≥25 years (aHR ranging from 0.62, 95% CI, 0.47-0.81 for age group 25-29 years to 0.24, 95% CI, 0.13-0.44 for age group ≥50 years), at least primary education level (aHR ranging from aHR = 0.77, 95% CI, 0.62-0.94 for primary education level to 0.50, 95% CI, 0.34-0.75 for post-secondary education level), and having a BMI ≥ 30 (aHR = 0.28, 95% CI, 0.15-0.51). CONCLUSION:The risk of loss to follow up increased with time and was higher among patients who started ART within seven days following HIV diagnosis, higher among patients without a telephone set, lower among patients aged ≥ 25 years, lower among patients with at least primary education and lower among patients with BMI of ≥ 30. In this era of T&T, it will be important for HIV programs to initiate and continue enhanced therapeutic education programs that target high risk groups, as well as leveraging on mHealth to improve patients' retention on ART throughout the cascade of care

Data for: “Loss to follow-up and associated factors in an HIV vaccine preparedness cohort study in Masaka, Uganda”

A quantitative dataset collected as part of an on-going HIV vaccine preparedness study “The PrEPVacc Registration Cohort”. The study was set up at sites in Tanzania, Mozambique, South Africa, and Uganda to prepare a population of HIV negative individuals at risk of acquiring HIV for possible participation in the PrEPVacc HIV vaccine efficacy trial. In Uganda, the study is conducted at the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit’s clinical research site in Masaka city, Masaka district. This dataset only includes information from the Masaka registration cohort collected between July 2018 and March 2021. It contains information on demographic, HIV risk behavioural characteristics and study schedule adherence data/ LTFU data. Participants were considered LTFU if they missed two or more consecutive scheduled study visits and failed to attend further study visits after at least three documented attempts

Predictors of Loss to Follow-Up in an HIV Vaccine Preparedness Study in Masaka, Uganda.

BACKGROUND: High participant retention is essential to achieve adequate statistical power for clinical trials. We assessed participant retention and predictors of loss to follow-up (LTFU) in an HIV vaccine-preparedness study in Masaka, Uganda. METHODS: Between July 2018 and March 2021, HIV sero-negative adults (18-45 years) at high risk of HIV infection were identified through HIV counselling and testing (HCT) from sex-work hotspots along the trans-African highway and fishing communities along the shores of Lake Victoria. Study procedures included collection of baseline socio-demographic data, quarterly HCT, and 6-monthly collection of sexual risk behaviour data. Retention strategies included collection of detailed locator data, short clinic visits (1-2 h), flexible reimbursement for transport costs, immediate (≤7 days) follow-up of missed visits via phone and/or home visits, and community engagement meetings. LTFU was defined as missing ≥2 sequential study visits. Poisson regression models were used to identify baseline factors associated with LTFU. RESULTS: 672 participants were included in this analysis. Of these, 336 (50%) were female and 390 (58%) were ≤24 years. The median follow-up time was 11 months (range: 0-31 months). A total 214 (32%) participants were LTFU over 607.8 person-years of observation (PYO), a rate of 35.2/100 PYO. LTFU was higher in younger participants (18-24 years versus 35-45 years, adjusted rate ratio (aRR) = 1.29, 95% confidence interval (CI) 0.80-2.11), although this difference was not significant. Female sex (aRR = 2.07, 95% CI, 1.51-2.84), and recreational drug use (aRR = 1.61, 95% CI, 1.12-2.34) were significantly associated with increased LTFU. Engagement in transactional sex was associated with increased LTFU (aRR = 1.36, 95% CI, 0.97-1.90) but this difference was not significant. LTFU was higher in 2020-2021 (the period of COVID-19 restrictions) compared to 2018-2019 (aRR = 1.54, 1.17-2.03). Being Muslim or other (aRR = 0.68, 95% CI 0.47-0.97) and self-identification as a sex worker (aRR = 0.47, 95% CI, 0.31-0.72) were associated with reduced LTFU. CONCLUSION: We observed a high LTFU rate in this cohort. LTFU was highest among women, younger persons, recreational drug users, and persons who engage in transactional sex. Efforts to design retention strategies should focus on these subpopulations