Henry Sunpath - Academia.edu (original) (raw)

Papers by Henry Sunpath

Public health action, Jun 1, 2024

PROTEOMICS – Clinical Applications

PurposeElevated levels of inflammation associated with human immunodeficiency virus (HIV) infecti... more PurposeElevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age‐related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH.Experimental designWe profiled 73 inflammation‐related protein markers and assessed their associations with chronological age, sex, and CD4+ cell count among 87 black South African PWH before antiretroviral therapy (ART).ResultsWe identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4+ cell count, and age respectively. Twelve out of 14 age‐associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age‐associated proteins such as CST5, CCL23, SLAMF1, MMP‐1, MCP‐1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neuroco...

Health and Quality of Life Outcomes, Aug 20, 2023

Research Square (Research Square), Nov 9, 2020

Background: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV in... more Background: The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38•7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. Methods: A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included le hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess delity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. Results: Mkuze and Jozini clinics increased VL performance overall from 33•9% and 35•3% to 75•8% and 72•4%, respectively which was signi cantly greater than the increases in the comparison clinics (RR 1•86 and 1•68, p<0•01). VL suppression rates similarly increased overall by 39•3% and 36•2% (RR 1•84 and 1•70, p<0•01). The Chart Intervention phase showed signi cant increases in delity 16 months after implementation. Conclusions: The packaged intervention improved VL performance and suppression rates overall but was signi cant in Mkuze and Jozini. Larger sustained efforts will be needed to have a similar impact throughout the province.

Open Forum Infectious Diseases, Jul 1, 2023

Background: Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence ... more Background: Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence in persons with HIV (PWH). This association has not been evaluated using tenofovir diphosphate in dried blood spots (TFV-DP in DBS), a biomarker of cumulative ART adherence and exposure. Methods: Within a prospective South African cohort of treatment-naïve PWH initiating ART, a subset of participants with measured TFV-DP in DBS values were assessed for food insecurity status. Bivariate and multivariate median-based regression analysis compared the association between food insecurity and TFV-DP concentrations in DBS adjusting for age, gender, ethnicity, medication possession ratio (MPR), and estimated glomerular filtration rate. Results: Drug concentrations were available for 285 study participants. Overall, 62 (22%) PWH reported worrying about food insecurity and 44 (15%) reported not having enough food to eat in the last month. The crude median concentrations of TFV-DP in DBS differed significantly between those who expressed food insecurity worry versus those who did not (599 [IQR 417-783] vs. 716 [IQR 453-957] fmol/punch; p=0.032). In adjusted median-based regression, those with food insecurity worry had concentrations of TFV-DP that were 155 (95% CI:-275 to-35; p=0.012) fmol/punch lower than those who did not report food insecurity worry. Age and MPR remained significantly associated with TFV-DP. Conclusion: In this study, food insecurity worry is associated with lower cumulative TFV-DP ART concentrations in South African PWH. This highlights the role of food insecurity, as social determinant of HIV outcomes including ART failure and resistance.

Research Square (Research Square), Oct 28, 2020

The Journal of Infectious Diseases, Dec 1, 2007

Wiley-VCH Verlag GmbH & Co. KGaA eBooks, Dec 21, 2009

Page 1. Part Three Clinical Issues AIDS and Tuberculosis: A Deadly Liaison. Edited by Stefan HE K... more Page 1. Part Three Clinical Issues AIDS and Tuberculosis: A Deadly Liaison. Edited by Stefan HE Kaufmann and Bruce D. Walker Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-32270-1 Page 2. ...

South African Medical Journal, Mar 31, 2021

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

AIDS Research and Human Retroviruses, Dec 1, 2017

The delay between first-line antiretroviral therapy (ART) failure and initiation of second-line A... more The delay between first-line antiretroviral therapy (ART) failure and initiation of second-line ART in resource-limited settings can be prolonged. Increasing evidence links delayed antiretroviral switch with increased risk for opportunistic infection (OI) and death, particularly in patients with advanced HIV at the time of first-line failure. As access to viral load (VL) monitoring widens beyond a few countries, mechanisms are needed to optimize the use of routine virologic monitoring and assure that first-line regimen failure results in prompt second-line switch. For patients with advanced HIV or OI at the time of first-line failure, a targeted fast track to second-line ART should be considered, involving a switch to second-line ART during a single visit. To derive the maximum benefit from both the current expansion of VL monitoring and the falling costs of second-line ART, clinics and healthcare workers should be given the tools and training to detect and switch patients with regimen failure before HIV disease progression.

The Journal of Infectious Diseases, Aug 6, 2013

Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloprotein... more Background. Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods. Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results. Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIVuninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). Conclusions. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.

Title: Case Management and Clinical Outcomes of People Living with HIV and Admitted to a State-ai... more Title: Case Management and Clinical Outcomes of People Living with HIV and Admitted to a State-aided District Hospital in Durban, South Africa in 2007. Introduction: A proportion of the many patients who have advanced AIDS in South Africa present for the first time requiring admission to hospital, the number of which are limited by the availability of beds. Novel ways were developed to offer subacute inpatient care at Siyaphila, a facility linked to McCord Hospital in Durban to provide expedited or immediate antiretroviral therapy (ART) (exposed) for patients with advanced disease before their discharge (ART group). Different components of palliative care were offered for those who did not enter the inpatient ART programme or who were terminally ill (non-ART group) (non-exposed). Aim: The aim of the study is to describe the clinical condition, inpatient case management and outcomes before discharge of people living with HIV admitted to Siyaphila in order to assist in developing appropriate protocols for inpatient care. Methods: This was an observational, analytic, cohort study using a convenience sample of all patients consecutively admitted to Siyaphila during nine months in 2006/2007. Prevalence of AIDS defining conditions at Siyaphila, time taken to progress from one stage of care to another and outcomes for the two groups before discharge were determined. Univariate and multivariate logistic regression analysis was performed on the ART group to identify risk factors for mortality before discharge. A comparison between the ART and non-ART group was also undertaken. Results: Among the cohort of 405 PLHIV enrolled at Siyaphila during the study period only 171 (42%) were initiated on ART immediately. In all patients, tuberculosis (251; 62%) was the most common opportunistic infection followed by cryptococcal meningitis (68; 17%) and Pneumocystis pneumonia (28; 7%). The mean baseline CD4 cell count was 84 celis/uL for the non-ART group and 55 celis/uL for the ART group. (p <0.01) The median time from initial admission until discharge was 13 days in the non-ART group and 18 days in the ART group. The mortality before discharge among the non-ART group was 24% compared to 6% among the ART group. (p =0.001). The median number of days before ART was initiated was 14 days. Immune reconstitution inflammatory syndrome was diagnosed in seven patients (4%) among the admissions but caused no deaths. In the multivariate analysis, the odds ratio for mortality for patients under 40 years was 0.1 (95% Confidence Interval : 0.01-0.9). Conclusions: Subacute care offered at Siyaphila provides an entry point into the ART programme for non-ambulatory patients who in the KwaZulu-Natal context have low ART uptake after discharge. The findings of this study should be adopted as the best clinical practice for PLHIV and AIDS admitted in the late stages of the disease. 0Nords 423) Title: Case Management and Clinical Outcomes of People Living with HIV and Admitted to a State-aided District Hospital in Durban, South Africa in 2007. Introduction: A proportion of the many patients who have advanced AIDS in South Africa present for the first time requiring admission to hospital, the number of which are limited by the availability of beds. Novel ways were developed to offer subacute inpatient care at Siyaphila, a facility linked to McCord Hospital in Durban to provide expedited or immediate antiretroviral therapy (ART) (exposed) for patients with advanced disease before their discharge (ART group). Different components of palliative care were offered for those who did not enter the inpatient ART programme or who were terminally ill (non-ART group) (non-exposed). Aim: The aim of the study is to describe the clinical condition , inpatient case management and outcomes before discharge of people living with HIV admitted to Siyaphila in order to assist in developing appropriate protocols for inpatient care. Methods: This was an observational , analytic, cohort study using a convenience sample of all patients consecutively admitted to Siyaphila during nine months in 2006/2007. Prevalence of AIDS defining conditions at Siyaphila , time taken to progress from one stage of care to another and outcomes for the two groups before discharge were iii determined. Univariate and mUltivariate logistic regression analysis was performed on the ART group to identify risk factors for mortality before discharge. A comparison between the ART and non-ART group was also undertaken. Results: Among the cohort of 405 PLHIV enrolled at Siyaphila during the study period only 171 (42%) were initiated on ART immediately. In all patients, tuberculosis (251; 62%) was the most common opportunistic infection followed by cryptococcal meningitis (68; 17%) and Pneumocystis pneumonia (28; 7%). The mean baseline CD4 cell count was 84 celis/uL for the non-ART group and 55 celis/uL for the ART group. (p <0.01) The median time from initial admission until discharge was 13 days in the non-ART group and 18 days in the ART group. The mortality before discharge among the non-ART group was 24% compared to 6% among the ART group. (p =0.001). The median number of days before ART was initiated was 14 days. Immune reconstitution inflammatory syndrome was diagnosed in seven patients (4%) among the admissions but caused no deaths. In the mUltivariate analysis, the odds ratio for mortality for patients under 40 years was 0.1

PLOS ONE, Nov 20, 2012

Background: With improved access to pediatric antiretroviral therapy (ART) in resource-limited se... more Background: With improved access to pediatric antiretroviral therapy (ART) in resource-limited settings, more children could experience first-line ART treatment failure. Methods: We performed a retrospective cohort analysis using electronic medical records from HIV-infected children who initiated ART at McCord Hospital's Sinikithemba Clinic in KwaZulu-Natal, South Africa, from August 2003 to December 2010. We analyzed all records from children who began second-line ART due to first-line treatment failure. We used logistic regression to compare viral outcomes in Protease Inhibitor (PI)-based versus Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based second-line ART, controlling for time on first-line ART, sex, and whether HIV genotyping guided the regimen change. Results: Of the 880 children who initiated ART during this time period, 80 (9.1%) switched to second-line ART due to therapeutic failure of first-line ART after a median of 95 weeks (IQR 65-147 weeks). Eight (10%) of the failures received NNRTI-based second-line ART, all of whom failed a PI-based first-line regimen. Seventy (87.5%) received PI-based secondline ART, all of whom failed a NNRTI-based first-line regimen. Two children (2.5%) received non-standard dual therapy as second-line ART. Six months after switching ART regimens, the viral suppression rate was significantly higher in the PI group (82%) than in the NNRTI group (29%; p = 0.003). Forty-one children (51%) were tested for genotypic resistance prior to switching to second-line ART. There was no significant difference in six month viral suppression (p = 0.38) between children with and without genotype testing. Conclusion: NNRTI-based second-line ART carries a high risk of virologic failure compared to PI-based second-line ART.

BMC Infectious Diseases

BackgroundThere is poor viral load monitoring (VLM) and inadequate management of virological fail... more BackgroundThere is poor viral load monitoring (VLM) and inadequate management of virological failure in HIV-positive individuals on antiretroviral therapy in rural KwaZulu-Natal, South Africa. This could be contributing to increasing HIV drug resistance in the setting. This study aims to investigate the clinical and process impediments in VLM within the health system and to evaluate a quality improvement package (QIP) to address the identified gaps. The QIP comprises (i) a designated viral load champion responsible for administrative management and triaging of viral load results (ii) technological enhancement of the routine clinic-based Three Interlinked Electronic Register (TIER.Net) to facilitate daily automatic import of viral load results from the National Health Service Laboratory to TIER.Net (iii) development of a dashboard system to support VLM.Methods/designThe study will evaluate the effectiveness of the QIP compared to current care for improving VLM and virological suppres...

The Lancet. Infectious diseases, 2016

Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatm... more Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used ...

The Journal of Infectious Diseases, Sep 15, 2008

PubMed, Aug 1, 2006

Objective: To determine the incidence of and predisposing risk factors for lactic acidosis in HIV... more Objective: To determine the incidence of and predisposing risk factors for lactic acidosis in HIV-infected patients on antiretroviral drugs in South Africa. Design: Observational case series. Setting: Sinikithemba HIV Clinic, McCord Hospital, Durban. Subjects: Eight hundred and ninety-one HIV-positive patients on highly active antiretroviral therapy (HAART) during an 18-month period commencing in January 2004. Measurements and results: Fourteen cases of lactic acidosis (incidence rate of 19 (95% confidence interval (CI): 9-29) cases per 1,000 person-years of treatment) were reported. All cases were female, with a median age of 36 years and a median weight of 81 kg. The median time on HAART before developing lactic acidosis was 7.5 months and the median peak lactate level was 9.3 mmol/l. All cases were on stavudine (d4T), lamivudine (3TC) and 1 non-NRTI. The case mortality rate was 29% (4 patients). Conclusions: The incidence rate is higher than reported in studies in developed countries. This may be due to d4T, which is recommended as a first-line antiretroviral drug in South Africa. This implication raises the question whether it is an appropriate drug in first-line treatment of patients with predisposing risk factors such as female gender and being overweight.

Southern African Journal of Hiv Medicine, Aug 31, 2021

When the novel coronavirus emerged in late 2019, much was unknown about its transmission, treatme... more When the novel coronavirus emerged in late 2019, much was unknown about its transmission, treatment and trajectory. In response to the rapidly growing case numbers and global spread, the World Health Organization declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern on 30 January 2020. 1 At the time, there was widespread uncertainty and fear about the mode of spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to hysteria and responses such as washing down groceries and other measures that were ultimately discarded. Early on, there were no known treatments for COVID-19, and in many places around the world, medications that ultimately proved ineffective-like hydroxychloroquine-were frequently administered out of desperation. 2,3 In addition, it soon became clear that COVID-19 was disproportionately affecting key populations such as racial and ethnic minorities in the United States (US) and other countries and the poor all around the world. In many ways, these early responses to COVID-19 were eerily reminiscent of the world's first tentative responses to HIV/AIDS (Box 1).

Public health action, Dec 21, 2020

Delayed identification and response to virologic failure in case of first-line antiretroviral the... more Delayed identification and response to virologic failure in case of first-line antiretroviral therapy (ART) in resource-limited settings is a threat to the health of HIV-infected patients. There is a need for the implementation of an effective, standardized response pathway in the public sector. Discussion: We evaluated published cohorts describing virologic failure on first-line ART. We focused on gaps in the detection and management of treatment failure, and posited ways to close these gaps, keeping in mind scalability and standardization. Specific shortcomings repeatedly recorded included early loss to follow-up (>20%) after recognized first-line ART virologic failure; frequent delays in confirmatory viral load testing; and excessive time between the confirmation of first-line ART failure and initiation of second-line ART, which exceeded 1 year in some cases. Strategies emphasizing patient tracing, resistance testing, drug concentration monitoring, adherence interventions, and streamlined response pathways for those failing therapy are further discussed. Conclusion: Comprehensive, evidence-based, clinical operational plans must be devised based on findings from existing research and further tested through implementation science research. Until this standard of evidence is available and implemented, high rates of losses from delays in appropriate switch to second-line ART will remain unacceptably common and a threat to the success of global HIV treatment programs.

Journal of Antimicrobial Chemotherapy, Mar 10, 2021

ObjectivesThere is conflicting evidence on the impact of pre-existing HIV drug resistance mutatio... more ObjectivesThere is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRMs) in patients infected with non-B subtype virus.MethodsWe performed a case–cohort substudy of the AIDS Drug Resistance Surveillance Study, which enrolled South African patients initiating first-line efavirenz/emtricitabine/tenofovir. Pre-ART DRMs were detected by Illumina sequencing of HIV pol and DRMs present at <20% of the viral population were labelled as minority variants (MVs). Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of virological failure (VF), defined as confirmed HIV-1 RNA ≥1000 copies/mL after ≥5 months of ART.ResultsThe evaluable population included 178 participants from a randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the subcohort, 16% of participants harboured ≥1 majority DRM. The presence of any majority DRM was associated with a 3-fold greater risk of VF (P = 0.002), which increased to 9.2-fold (P < 0.001) in those with <2 active drugs. Thirteen percent of participants harboured MV DRMs in the absence of majority DRMs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity but reduced the specificity of predicting VF.ConclusionsIn a South African cohort, the presence of majority DRMs increased the risk of VF, especially for participants receiving <2 active drugs. The detection of drug-resistant MVs alone did not predict an increased risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF.