HIV Disease Progression Among Antiretroviral Therapy Patients in Zimbabwe: A Multistate Markov Model.

Background: Antiretroviral therapy (ART) impact has prolonged survival of people living with HIV. We evaluated HIV disease progression among ART patients using routinely collected patient-level data between 2004 and 2017 in Zimbabwe. Methods: We partitioned HIV disease progression into four transient CD4 cell counts states: state 1 (CD4 ≥ 500 cells/μl), state 2 (350 cells/μl ≤ CD4 < 500 cells/μl), state 3 (200 cells/μl ≤ CD4 < 350 cells/μl), state 4 (CD4 < 200 cells/μl), and the absorbing state death (state 5). We proposed a semiparametric time-homogenous multistate Markov model to estimate bidirectional transition rates. Covariate effects (age, gender, ART initiation period, and health facility level) on the transition rates were assessed. Results: We analyzed 204,289 clinic visits by 63,422 patients. There were 24,325 (38.4%) patients in state 4 (CD4 < 200) at ART initiation, and 7,995 (12.6%) deaths occurred by December 2017. The overall mortality rate was 3.9 per 100 person-years. The highest mortality rate of 5.7 per 100 person-years (4,541 deaths) was from state 4 (CD4 < 200) compared to other states. Mortality rates decreased with increase in time since ART initiation. Health facility type was the strongest predictor for immune recovery. Provincial or central hospital patients showed a diminishing dose-response effect on immune recovery by state from a hazard ratio (HR) of 8.30 [95% confidence interval (95% CI), 6.64-10.36] (state 4 to 3) to HR of 3.12 (95% CI, 2.54-4.36) (state 2 to 1) compared to primary healthcare facilities. Immune system for male patients was more likely to deteriorate, and they had a 32% increased mortality risk (HR, 1.32; 95% CI, 1.23-1.42) compared to female patients. Elderly patients (45+ years) were more likely to immune deteriorate compared to 25-34 years age group: HR, 1.35; 95% CI, 1.18-1.54; HR, 1.56; 95% CI, 1.34-1.81 and HR, 1.53; 95% CI, 1.32-1.79 for states 1 to 2, state 2 to 3, and states 3 to 4, respectively. Conclusion: Immune recovery was pronounced among provincial or central hospitals. Male patients with lower CD4 cell counts were at a higher risk of immune deterioration and mortality, while elderly patients were more likely to immune deteriorate. Early therapeutic interventions when the immune system is relatively stable across gender and age may contain mortality and increase survival outcomes. Interventions which strengthen ART services in primary healthcare facilities are essential

Competing risk of mortality on loss to follow-up outcome among patients with HIV on ART: a retrospective cohort study from the Zimbabwe national ART programme.

OBJECTIVE: To determine the loss to follow-up (LTFU) rates at different healthcare levels after antiretroviral therapy (ART) services decentralisation among ART patients who initiated ART between 2004 and 2017 using the competing risk model in addition to the Kaplan-Meier and Cox regressions analysis. DESIGN: A retrospective cohort study. SETTING: The study was done in Zimbabwe using a nationwide routinely collected HIV patient-level data from various health levels of care facilities compiled through the electronic patient management system (ePMS). PARTICIPANTS: We analysed 390 771 participants aged 15 years and above from 538 health facilities. OUTCOMES: The primary endpoint was LTFU defined as a failure of a patient to report for drug refill for at least 90 days from last appointment date or if the patient missed the next scheduled visit date and never showed up again. Mortality was considered a secondary outcome if a patient was reported to have died. RESULTS: The total exposure time contributed was 1 544 468 person-years. LTFU rate was 5.75 (95% CI 5.71 to 5.78) per 100 person-years. Adjustment for the competing event independently increased LTFU rate ratio in provincial and referral (adjusted sub-HRs (AsHR) 1.22; 95% CI 1.18 to 1.26) and district and mission (AsHR 1.47; 95% CI 1.45 to 1.50) hospitals (reference: primary healthcare); in urban sites (AsHR 1.61; 95% CI 1.59 to 1.63) (reference: rural); and among adolescence and young adults (15-24 years) group (AsHR 1.19; 95% CI 1.16 to 1.21) (reference: 35-44 years). We also detected overwhelming association between LTFU and tuberculosis-infected patients (AsHR 1.53; 95% CI 1.45 to 1.62) (reference: no tuberculosis). CONCLUSIONS: We have observed considerable findings that 'leakages' (LTFU) within the ART treatment cascade persist even after the decentralisation of health services. Risk factors for LTFU reflect those found in sub-Saharan African studies. Interventions that retain patients in care by minimising any 'leakages' along the treatment cascade are essential in attaining the 90-90-90 UNAIDS fast-track targets

Loss to Follow-Up Risk among HIV Patients on ART in Zimbabwe, 2009-2016: Hierarchical Bayesian Spatio-Temporal Modeling

Loss to follow-up (LTFU) is a risk factor for poor outcomes in HIV patients. The spatio-temporal risk of LTFU is useful to identify hotspots and guide policy. Secondary data on adult HIV patients attending a clinic in provinces of Zimbabwe between 2009 and 2016 were used to estimate the LTFU risk in each of the 10 provinces. A hierarchical Bayesian spatio-temporal Poisson regression model was fitted using the Integrated Nested Laplace Approximation (INLA) package with LTFU as counts adjusting for age, gender, WHO clinical stage, tuberculosis coinfection and duration on ART. The structured random effects were modelled using the conditional autoregression technique and the temporal random effects were modelled using first-order random walk Gaussian priors. The overall rate of LTFU was 22.7% (95%CI: 22.6/22.8) with Harare (50.28%) and Bulawayo (31.11%) having the highest rates. A one-year increase in the average number of years on ART reduced the risk of LTFU by 35% (relative risk (RR) = 0.651; 95%CI: 0.592-0.712). In general, the provinces with the highest exceedance LTFU risk were Matabeleland South and Matabeleland North. LTFU is one of the drawbacks of HIV prevention. Interventions targeting high-risk regions in the southern and northern regions of Zimbabwe are a priority. Community-based interventions and programmes which mitigate LTFU risk remain essential in the global HIV prevention campaign

A review of multistate modelling approaches in monitoring disease progression: Bayesian estimation using the Kolmogorov-Chapman forward equations.

There are numerous fields of science in which multistate models are used, including biomedical research and health economics. In biomedical studies, these stochastic continuous-time models are used to describe the time-to-event life history of an individual through a flexible framework for longitudinal data. The multistate framework can describe more than one possible time-to-event outcome for a single individual. The standard estimation quantities in multistate models are transition probabilities and transition rates which can be mapped through the Kolmogorov-Chapman forward equations from the Bayesian estimation perspective. Most multistate models assume the Markov property and time homogeneity; however, if these assumptions are violated, an extension to non-Markovian and time-varying transition rates is possible. This manuscript extends reviews in various types of multistate models, assumptions, methods of estimation and data features compatible with fitting multistate models. We highlight the contrast between the frequentist (maximum likelihood estimation) and the Bayesian estimation approaches in the multistate modeling framework and point out where the latter is advantageous. A partially observed and aggregated dataset from the Zimbabwe national ART program was used to illustrate the use of Kolmogorov-Chapman forward equations. The transition rates from a three-stage reversible multistate model based on viral load measurements in WinBUGS were reported

Markov modelling of viral load adjusting for CD4 orthogonal variable and multivariate conditional autoregressive mapping of the HIV immunological outcomes among ART patients in Zimbabwe

BACKGROUND: This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying "incremental transients states" variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU). METHODS: Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients' retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model. RESULTS: The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual's VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North. CONCLUSION: With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030

Microbiota identified from preserved Anopheles

peer reviewedBackground: Mosquito species from the Anopheles gambiae complex and the Anopheles funestus group are dominant African malaria vectors. Mosquito microbiota play vital roles in physiology and vector competence. Recent research has focused on investigating the mosquito microbiota, especially in wild populations. Wild mosquitoes are preserved and transported to a laboratory for analyses. Thus far, microbial characterization post-preservation has been investigated in only Aedes vexans and Culex pipiens. Investigating the efficacy of cost-effective preservatives has also been limited to AllProtect reagent, ethanol and nucleic acid preservation buffer. This study characterized the microbiota of African Anopheles vectors: Anopheles arabiensis (member of the An. gambiae complex) and An. funestus (member of the An. funestus group), preserved on silica desiccant and RNAlater® solution. Methods: Microbial composition and diversity were characterized using culture-dependent (midgut dissections, culturomics, MALDI-TOF MS) and culture-independent techniques (abdominal dissections, DNA extraction, next-generation sequencing) from laboratory (colonized) and field-collected mosquitoes. Colonized mosquitoes were either fresh (non-preserved) or preserved for 4 and 12 weeks on silica or in RNAlater®. Microbiota were also characterized from field-collected An. arabiensis preserved on silica for 8, 12 and 16 weeks. Results: Elizabethkingia anophelis and Serratia oryzae were common between both vector species, while Enterobacter cloacae and Staphylococcus epidermidis were specific to females and males, respectively. Microbial diversity was not influenced by sex, condition (fresh or preserved), preservative, or preservation time-period; however, the type of bacterial identification technique affected all microbial diversity indices. Conclusions: This study broadly characterized the microbiota of An. arabiensis and An. funestus. Silica- and RNAlater®-preservation were appropriate when paired with culture-dependent and culture-independent techniques, respectively. These results broaden the selection of cost-effective methods available for handling vector samples for downstream microbial analyses

Assessing spatial patterns of HIV prevalence and interventions in semi-urban settings in South Africa. Implications for spatially targeted interventions

DATA AVAILABITY STATEMENT : The data presented in this study are available on request from the corresponding author. The data are not publicly available as permission from the gatekeepers is required for access.Equitable allocation of resources targeting the human immunodeficiency virus (HIV) at the local level requires focusing interventions in areas of the greatest need. Understanding the geographical variation in the HIV epidemic and uptake of selected HIV prevention and treatment programmes are necessary to identify such areas. Individual-level HIV data were obtained from a 2012 national HIV survey in South Africa. Spatial regression models on each outcome measure (HIV infection, sub-optimal condom use or non-anti-retroviral treatment (ART) adjusted for spatial random effects at the ward level were fitted using WINBUGS software. In addition, ward-level data was utilized to estimate condom use coverage and ART initiation rates which were obtained from routinely collected data in 2012. Ordinary Kriging was used to produce smoothed maps of HIV infection, condom use coverage and ART initiation rates. HIV infection was associated with individuals undertaking tertiary education [posterior odds ratio (POR): 19.53; 95% credible intervals (CrI): 3.22- 84.93]. Sub-optimal condom use increased with age (POR: 1.09; 95%CrI: 1.06-1.11) and was associated with being married (POR: 4.14; 95%CrI: 1.23-4.28). Non-ART use was associated with being married (POR: 6.79; 95%CrI: 1.43-22.43). There were clusters with high HIV infection, sub-optimal condom use, and non- ART use in Ekurhuleni, an urban and semi-urban district in Gauteng province, South Africa. Findings show the need for expanding condom programmes and/or strengthening other HIV prevention programmes such as pre-exposure prophylaxis and encouraging sustained engagement in HIV care and treatment in the identified areas with the greatest need in Ekurhuleni Metropolitan Municipality.This PhD work is based on the research supported by the Department of Science and Innovation and the National Research Foundation (NRF).https://www.geospatialhealth.net/index.php/ghhj2023Statistic

The use of 18F-FDG PET/CT metabolic parameters in predicting overall survival in patients undergoing restaging for malignant melanoma

Malignant melanoma is one of the more aggressive cancers in the skin, with an increasing incidence every year. Melanoma has a better prognosis if diagnosed early and survival tends to decrease once the disease has metastasized. Positron emission tomography (PET) with 2-[18F]fluoro2-deoxy-D-glucose (18F-FDG) has been used extensively over the past two decades in staging and assessing responses to therapy in patients with melanoma. Metabolic PET parameters have been demonstrated to be independent prognostic factors for progression-free survival (PFS) and overall survival (OS) in different malignancies, melanoma included. In our study, we evaluated the metabolic parameters of 18F-FDG PET/CT (flourodeoxyglucose positron emission tomography/computed tomography) in predicting the overall survival in patients with malignant melanoma who presented for restaging. Metabolic PET parameters (maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) of the primary tumor, as well as whole-body MTV and TLG of the metastatic disease, were measured. Survival curves for OS were constructed and mortality rates were determined using the different PET variables. Forty-nine patients who presented for a PET/CT restaging in melanoma were included in this study. We found that non-survivors had significantly higher median MTV (11.86 cm3 vs. 5.68 cm3 ; p-value = 0.022), TLG (3125 vs. 14; p-value = 0.0357), whole-body MTV (53.9 cm3 vs. 14.4 cm3 ; p-value = 0.0076) and whole-body TLG (963.4 vs. 114.6; p-value = 0.0056). This demonstrated that high MTV and TLG values of the primary tumor and whole-body TLG as quantified by 18F-FDG PET/CT were prognostic factors for overall survival. The findings may potentially guide clinicians in decision making and identifying patients with a poorer prognosis.https://www.mdpi.com/journal/diagnosticsdm2022Nuclear Medicin

Mapping evidence on the burden of breast, cervical, and prostate cancers in Sub-Saharan Africa : a scoping review

BACKGROUND : Cancer remains a major public health problem, especially in Sub-Saharan Africa (SSA) where the provision of health care is poor. This scoping review mapped evidence in the literature regarding the burden of cervical, breast and prostate cancers in SSA. METHODS : We conducted this scoping review using the Arksey and O’Malley framework, with five steps: identifying the research question; searching for relevant studies; selecting studies; charting the data; and collating, summarizing, and reporting the data. We performed all the steps independently and resolved disagreements through discussion. We used Endnote software to manage references and the Rayyan software to screen studies. RESULTS : We found 138 studies that met our inclusion criteria from 2,751 studies identified through the electronic databases. The majority were retrospective studies of mostly registries and patient files (n = 77, 55.8%), followed by cross-sectional studies (n = 51, 36.9%). We included studies published from 1990 to 2021, with a sharp increase from 2010 to 2021. The quality of studies was overall satisfactory. Most studies were done in South Africa (n = 20) and Nigeria (n = 17). The majority were on cervical cancer (n = 93, 67.4%), followed by breast cancer (67, 48.6%) and the least were on prostate cancer (48, 34.8%). Concerning the burden of cancer, most reported prevalence and incidence. We also found a few studies investigating mortality, disability-adjusted life years (DALYs), and years of life lost (YLL). CONCLUSIONS : We found many retrospective record review cross-sectional studies, mainly in South Africa and Nigeria, reporting the prevalence and incidence of cervical, breast and prostate cancer in SSA. There were a few systematic and scoping reviews. There is a scarcity of cervical, breast and prostate cancer burden studies in several SSA countries. The findings in this study can inform policy on improving the public health systems and therefore reduce cancer incidence and mortality in SSA.The National Science Foundation.https://www.frontiersin.org/journals/public-healthdm2022School of Health Systems and Public Health (SHSPH

Prevalence and factors associated with self-reported HIV testing among adolescent girls and young women in Rwanda : evidence from 2019/20 Rwanda Demographic and Health Survey

AVAILABILITY OF DATA AND MATERIALS : The dataset generated and analysed during the current study are not publicly available since we received a data access letter from the DHS team https://dhsprogram.com/ specifc to our project but are available from the DHS team upon request.BACKGROUND : HIV/AIDS remains a major public health problem globally. The majority of people living with HIV are from Sub-Saharan Africa, particularly adolescent girls and young women (AGYW) aged 15-24 years. HIV testing is crucial as it is the gateway to HIV prevention, treatment, and care; therefore this study determined the prevalence and factors associated with self-reported HIV testing among AGYW in Rwanda. METHODS : We conducted secondary data analysis on the AGYW using data extracted from the nationally representative population-based 2019/2020 cross-sectional Rwanda Demographic and Health Survey (DHS). We described the characteristics of study participants and determined the prevalence of HIV testing and associated factors using the multivariable logistic regression model. We adjusted all our analyses for unequal sampling probabilities using survey weights. RESULTS : There were a total of 5,732 AGYW, with the majority (57%) aged 15-19 years, 83% were not living with a man, 80% were from rural areas, 29% were from the East region, and 20% had a history of pregnancy. Self-reported HIV testing prevalence was 55.4% (95%CI: 53.7 to 57.0%). The odds of ever having an HIV test were significantly higher for those aged 20-24 years (aOR 2.87, 95%CI: 2.44 to 3.37); with higher education (aOR 2.41, 95%CI:1.48 to 3.93); who were rich (aOR 2.06, 95%CI:1.57 to 2.70); with access to at least one media (aOR 1.64, 95%CI: 1.14 to 2.37); who had ever been pregnant (aOR 16.12, 95%CI: 9.60 to 27.07); who ever had sex (aOR 2.40, 95%CI: 1.96 to 2.95); and those who had comprehensive HIV knowledge (aOR 1.34, 95%CI: 1.17 to 1.54). CONCLUSIONS : We report an unmet need for HIV testing among AGYW in Rwanda. We recommend a combination of strategies to optimize access to HIV testing services, especially among the 15-19 years adolescent girls, including facility-based testing, school and community outreach, awareness campaigns on HIV testing, and home-based testing through HIV self-testing.http://www.biomedcentral.com/bmcpublichealtham2023School of Health Systems and Public Health (SHSPH