Journal Article > ReviewFull Text
Int J Epidemiol. 2016 May 20; 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. 2016 May 20; Volume 46 (Issue 2); e21.; DOI:doi.org/10.1093/ije/dyw057
Journal Article > ResearchFull Text
Clin Infect Dis. 2018 March 4; Volume 66 (Issue suppl_2); S118-S125.; DOI:10.1093/cid/cix1140
Osler M, Hilderbrand K, Goemaere E, Ford NP, Smith M, et al.
Clin Infect Dis. 2018 March 4; Volume 66 (Issue suppl_2); S118-S125.; DOI:10.1093/cid/cix1140
BACKGROUND
Antiretroviral treatment (ART) has been massively scaled up to decrease human immunodeficiency virus (HIV)-related morbidity, mortality, and HIV transmission. However, despite documented increases in ART coverage, morbidity and mortality have remained substantial. This study describes trends in the numbers and characteristics of patients with very advanced HIV disease in the Western Cape, South Africa.
METHODS
Annual cross-sectional snapshots of CD4 distributions were described over 10 years, derived from a province-wide cohort of all HIV patients receiving CD4 cell count testing in the public sector. Patients with a first CD4 count <50 cells/µL in each year were characterized with respect to prior CD4 and viral load testing, ART access, and retention in ART care.
RESULTS
Patients attending HIV care for the first time initially constituted the largest group of those with CD4 count <50 cells/µL, dropping proportionally over the decade from 60.9% to 26.7%. By contrast, the proportion who were ART experienced increased from 14.3% to 56.7%. In patients with CD4 counts <50 cells/µL in 2016, 51.8% were ART experienced, of whom 76% could be confirmed to be off ART or had recent viremia. More than half who were ART experienced with a CD4 count <50 cells/µL in 2016 were men, compared to approximately one-third of all patients on ART in the same year.
CONCLUSIONS
Ongoing HIV-associated morbidity now results largely from treatment-experienced patients not being in continuous care or not being fully virologically suppressed. Innovative interventions to retain ART patients in effective care are an essential priority for the ongoing HIV response.
Antiretroviral treatment (ART) has been massively scaled up to decrease human immunodeficiency virus (HIV)-related morbidity, mortality, and HIV transmission. However, despite documented increases in ART coverage, morbidity and mortality have remained substantial. This study describes trends in the numbers and characteristics of patients with very advanced HIV disease in the Western Cape, South Africa.
METHODS
Annual cross-sectional snapshots of CD4 distributions were described over 10 years, derived from a province-wide cohort of all HIV patients receiving CD4 cell count testing in the public sector. Patients with a first CD4 count <50 cells/µL in each year were characterized with respect to prior CD4 and viral load testing, ART access, and retention in ART care.
RESULTS
Patients attending HIV care for the first time initially constituted the largest group of those with CD4 count <50 cells/µL, dropping proportionally over the decade from 60.9% to 26.7%. By contrast, the proportion who were ART experienced increased from 14.3% to 56.7%. In patients with CD4 counts <50 cells/µL in 2016, 51.8% were ART experienced, of whom 76% could be confirmed to be off ART or had recent viremia. More than half who were ART experienced with a CD4 count <50 cells/µL in 2016 were men, compared to approximately one-third of all patients on ART in the same year.
CONCLUSIONS
Ongoing HIV-associated morbidity now results largely from treatment-experienced patients not being in continuous care or not being fully virologically suppressed. Innovative interventions to retain ART patients in effective care are an essential priority for the ongoing HIV response.
Journal Article > ResearchFull Text
AIDS. 2010 February 20; Volume 24 (Issue 4); DOI:10.1097/QAD.0b013e328333bfb7
Boulle AM, van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, et al.
AIDS. 2010 February 20; Volume 24 (Issue 4); DOI:10.1097/QAD.0b013e328333bfb7
OBJECTIVES: We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment. DESIGN: This is an observational cohort study. METHODS: Since inception, patient-level clinical data have been prospectively captured on-site into an electronic patient information system. Patients with available civil identification numbers who were lost to follow-up were matched with the national death registry to ascertain their vital status. Corrected mortality estimates weighted these patients to represent all patients lost to follow-up. CD4 cell count outcomes were reported conditioned on continuous virological suppression. RESULTS: Seven thousand, three hundred and twenty-three treatment-naive adults (68% women) started ART between 2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006. Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died. Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9-24.3). Mortality fell over time as patients accessed care earlier (median CD4 cell count at enrolment increased from 43 cells/microl in 2001 to 131 cells/microl in 2006). Patients who remained virologically suppressed continued to gain CD4 cells at 5 years (median 22 cells/microl per 6 months). By 5 years, 14.0% of patients had failed virologically and 12.2% had been switched to second-line therapy. CONCLUSION: At a time of considerable debate about future global funding of ART programmes in resource-poor settings, this study has demonstrated substantial and durable clinical benefits for those able to access ART throughout this period, in spite of increasing loss to follow-up.
Journal Article > ResearchFull Text
J Int AIDS Soc. 2020 June 26; Volume 23 (Issue S2); e25530.; DOI:10.1002/jia2.25530
Osler M, Cornell M, Ford NP, Hilderbrand K, Goemaere E, et al.
J Int AIDS Soc. 2020 June 26; Volume 23 (Issue S2); e25530.; DOI:10.1002/jia2.25530
INTRODUCTION
Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa.
METHODS
We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age.
RESULTS
Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time.
CONCLUSIONS
Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade.
Few studies have systematically described population‐level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa.
METHODS
We analysed population‐wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre‐ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age.
RESULTS
Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time.
CONCLUSIONS
Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co‐infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade.
Journal Article > CommentaryFull Text
J Int AIDS Soc. 2014 April 28; Volume 17 (Issue 1); DOI:10.7448/IAS.17.1.18908
Osler M, Hilderbrand K, Hennessey C, Arendse J, Goemaere E, et al.
J Int AIDS Soc. 2014 April 28; Volume 17 (Issue 1); DOI:10.7448/IAS.17.1.18908
The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions.
Journal Article > ResearchFull Text
Bull World Health Organ. 2008 September 1; Volume 86 (Issue 9); 678-687.; DOI:18797643
Boulle AM, Bock P, Osler M, Cohen K, Channing L, et al.
Bull World Health Organ. 2008 September 1; Volume 86 (Issue 9); 678-687.; DOI:18797643
OBJECTIVE
To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART.
METHODS
The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART.
FINDINGS
By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than 50 cells/microl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART.
CONCLUSION
The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.
To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART.
METHODS
The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART.
FINDINGS
By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than 50 cells/microl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART.
CONCLUSION
The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.
Journal Article > ResearchFull Text
Antivir Ther. 2008 November 1; Volume 13 (Issue 7); 937-943.
Stead D, Osler M, Boulle AM, Rebe K, Meintjes GA
Antivir Ther. 2008 November 1; Volume 13 (Issue 7); 937-943.
BACKGROUND
In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T.
METHODS
GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.
RESULTS
In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.
CONCLUSIONS
This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.
In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T.
METHODS
GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate.
RESULTS
In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL.
CONCLUSIONS
This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.