Journal Article > LetterSubscription Only
Clin Infect Dis. 5 August 2023; ciad459.; DOI:10.1093/cid/ciad459
Schomaker M, Kerschberger B, Boulle AM
Clin Infect Dis. 5 August 2023; ciad459.; DOI:10.1093/cid/ciad459
Journal Article > ResearchAbstract Only
AIDS. 24 November 2022; Volume 37 (Issue 3); 513-522.; DOI:10.1097/QAD.0000000000003442
Patten GE, Euvrard J, Anderegg N, Boulle AM, Arendse KD, et al.
AIDS. 24 November 2022; Volume 37 (Issue 3); 513-522.; DOI:10.1097/QAD.0000000000003442
OBJECTIVE
Despite improved access to antiretroviral therapy (ART) for people with HIV (PWH), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PWH who are ART-experienced.
DESIGN
Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa.
METHODS
Using data from IeDEA Southern Africa, we included PWH from South Africa, initiating ART from 2004 to 2017 aged more than 5 years with a CD4+ cell count at ART start and at least one subsequent measure. We defined a gap as no visit for at least 18 months. Five states were defined: ‘AHD on ART’ (CD4+ cell count <200 cells/μl), ‘Clinically Stable on ART’ (CD4+ cell count ≥200 or if no CD4+ cell count, viral load <1000 copies/ml), ‘Early Gap’ (commencing ≤18 months from ART start), ‘Late Gap’ (commencing >18 months from ART start) and ‘Death’.
RESULTS
Among 32 452 PWH, men and those aged 15–25 years were more likely to progress to unfavourable states. Later years of ART start were associated with a lower probability of transitioning from AHD to clinically stable, increasing the risk of death following AHD. In stratified analyses, those starting ART with AHD in later years were more likely to re-engage in care with AHD following a gap and to die following AHD on ART.
CONCLUSION
In more recent years, those with AHD on ART were more likely to die, and AHD at re-engagement in care increased. To further reduce HIV-related mortality, efforts to address the challenges facing these more vulnerable patients are needed.
Despite improved access to antiretroviral therapy (ART) for people with HIV (PWH), HIV continues to contribute considerably to morbidity and mortality. Increasingly, advanced HIV disease (AHD) is found among PWH who are ART-experienced.
DESIGN
Using a multi-state model we examined associations between engagement with care and AHD on ART in South Africa.
METHODS
Using data from IeDEA Southern Africa, we included PWH from South Africa, initiating ART from 2004 to 2017 aged more than 5 years with a CD4+ cell count at ART start and at least one subsequent measure. We defined a gap as no visit for at least 18 months. Five states were defined: ‘AHD on ART’ (CD4+ cell count <200 cells/μl), ‘Clinically Stable on ART’ (CD4+ cell count ≥200 or if no CD4+ cell count, viral load <1000 copies/ml), ‘Early Gap’ (commencing ≤18 months from ART start), ‘Late Gap’ (commencing >18 months from ART start) and ‘Death’.
RESULTS
Among 32 452 PWH, men and those aged 15–25 years were more likely to progress to unfavourable states. Later years of ART start were associated with a lower probability of transitioning from AHD to clinically stable, increasing the risk of death following AHD. In stratified analyses, those starting ART with AHD in later years were more likely to re-engage in care with AHD following a gap and to die following AHD on ART.
CONCLUSION
In more recent years, those with AHD on ART were more likely to die, and AHD at re-engagement in care increased. To further reduce HIV-related mortality, efforts to address the challenges facing these more vulnerable patients are needed.
Journal Article > ResearchFull Text
AIDS Behav. 31 July 2022; Online ahead of print; DOI:10.1007/s10461-022-03772-9
Cassidy T, Cornell M, Makeleni B, Horsburgh CR, Trivino Duran L, et al.
AIDS Behav. 31 July 2022; Online ahead of print; DOI:10.1007/s10461-022-03772-9
Men have higher rates of attrition from antiretroviral therapy (ART) programs than women. In Khayelitsha, a high HIV prevalence area in South Africa, two public sector primary healthcare clinics offer services, including HIV testing and treatment, exclusively to men. We compared attrition from ART care among men initiating ART at these clinics with male attrition in six general primary healthcare clinics in Khayelitsha. We described baseline characteristics of patients initiating ART at the male and general clinics from 1 January 2014 to 31 March 2018. We used exposure propensity scores (generated based on baseline health and age) to match male clinic patients 1:1 to males at other clinics. The association between attrition (death or loss to follow-up, defined as no visits for nine months) and clinic type was estimated using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer, or dataset closure. Before matching, patients from male clinics (n = 784) were younger than males from general clinics (n = 2726), median age: 31.2 vs 35.5 years. Those initiating at male clinics had higher median CD4 counts at ART initiation [Male Clinic 1: 329 (IQR 210–431), Male Clinic 2: 364 (IQR 260–536), general clinics 258 (IQR 145–398), cells/ mm3. In the matched analysis (1451 person-years, 1568 patients) patients initiating ART at male clinics had lower attrition (HR 0.71; 95% CI 0.60–0.85). In separate analyses for each of the two male clinics, only the more established male clinic showed a protective effect. Male-only clinics reached younger, healthier men, and had lower ART attrition than general services. These findings support clinic-specific adaptations to create more male-friendly environments.
Journal Article > ResearchFull Text
J Int AIDS Soc. 23 June 2017; Volume 20 (Issue 1); DOI:10.7448/IAS.20.1.21327
Fenner L, Atkinson A, Boulle AM, Fox MP, Prozesky HW, et al.
J Int AIDS Soc. 23 June 2017; Volume 20 (Issue 1); DOI:10.7448/IAS.20.1.21327
Chronic immune activation due to ongoing HIV replication may lead to impaired immune responses against opportunistic infections such as tuberculosis (TB). We studied the role of HIV replication as a risk factor for incident TB after starting antiretroviral therapy (ART).
Journal Article > LetterFull Text
Clin Infect Dis. 23 April 2014; Volume 59 (Issue 3); DOI:10.1093/cid/ciu288
Patten GE, Cox V, Stinson K, Boulle AM, Wilkinson LS
Clin Infect Dis. 23 April 2014; Volume 59 (Issue 3); DOI:10.1093/cid/ciu288
Journal Article > ResearchFull Text
S Afr Med J. 1 September 2009
Cornell M, Technau KG, Fairall L, Wood R, Moultrie H, et al.
S Afr Med J. 1 September 2009
OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.
Journal Article > ResearchFull Text
AIDS. 10 September 2010; Volume 24 (Issue 14); DOI:10.1097/QAD.0b013e32833d45c5
Cornell M, Grimsrud A, Fairall L, Fox MP, van Cutsem G, et al.
AIDS. 10 September 2010; Volume 24 (Issue 14); DOI:10.1097/QAD.0b013e32833d45c5
OBJECTIVE: Little is known about the temporal impact of the rapid scale-up of large antiretroviral therapy (ART) services on programme outcomes. We describe patient outcomes [mortality, loss-to-follow-up (LTFU) and retention] over time in a network of South African ART cohorts. DESIGN: Cohort analysis utilizing routinely collected patient data. METHODS: Analysis included adults initiating ART in eight public sector programmes across South Africa, 2002-2007. Follow-up was censored at the end of 2008. Kaplan-Meier methods were used to estimate time to outcomes, and proportional hazards models to examine independent predictors of outcomes. RESULTS: Enrolment (n = 44 177, mean age 35 years; 68% women) increased 12-fold over 5 years, with 63% of patients enrolled in the past 2 years. Twelve-month mortality decreased from 9% to 6% over 5 years. Twelve-month LTFU increased annually from 1% (2002/2003) to 13% (2006). Cumulative LTFU increased with follow-up from 14% at 12 months to 29% at 36 months. With each additional year on ART, failure to retain participants was increasingly attributable to LTFU compared with recorded mortality. At 12 and 36 months, respectively, 80 and 64% of patients were retained. CONCLUSION: Numbers on ART have increased rapidly in South Africa, but the programme has experienced deteriorating patient retention over time, particularly due to apparent LTFU. This may represent true loss to care, but may also reflect administrative error and lack of capacity to monitor movements in and out of care. New strategies are needed for South Africa and other low-income and middle-income countries to improve monitoring of outcomes and maximize retention in care with increasing programme size.
Journal Article > ReviewFull Text
Int J Epidemiol. 20 May 2016; Volume 46 (Issue 2); e21.; DOI:doi.org/10.1093/ije/dyw057
Stinson K, Goemaere E, Coetzee D, van Cutsem G, Hilderbrand K, et al.
Int J Epidemiol. 20 May 2016; Volume 46 (Issue 2); e21.; DOI:doi.org/10.1093/ije/dyw057
Journal Article > ResearchFull Text
PLOS One. 28 February 2013; Volume 8 (Issue 2); e57611.; DOI:10.1371/journal.pone.0057611
Estill J, Egger M, Johnson LF, Gsponer T, Wandeler G, et al.
PLOS One. 28 February 2013; Volume 8 (Issue 2); e57611.; DOI:10.1371/journal.pone.0057611
OBJECTIVES
Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.
DESIGN
Mathematical modelling study based on data from ART programmes.
METHODS
We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained.
RESULTS
RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality.
CONCLUSIONS
VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.
DESIGN
Mathematical modelling study based on data from ART programmes.
METHODS
We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained.
RESULTS
RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality.
CONCLUSIONS
VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
Protocol > Research Protocol
Fernandez MAL, Schomaker M, Mason PR, Fesselet JF, Baudot Y, et al.
18 June 2012
BACKGROUND
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.