Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2015 November 1; Volume 19 (Issue 11); 1300-1304.; DOI:10.5588/ijtld.15.0015
Cox V, De Azevedo V, Stinson K, Wilkinson LS, Rangaka MX, et al.
Int J Tuberc Lung Dis. 2015 November 1; Volume 19 (Issue 11); 1300-1304.; DOI:10.5588/ijtld.15.0015
BACKGROUND
The World Health Organization recommends tuberculin skin tests (TSTs) where feasible to identify individuals most likely to benefit from isoniazid preventive therapy (IPT). The requirement for TST reading after 48–72 h by a trained nurse is a barrier to implementation and increases loss to follow-up.
METHODS
Patients with human immunodeficiency virus (HIV) infection were recruited from a primary care clinic in South Africa and trained by a lay counsellor to interpret their own TST. The TST was placed by a nurse, and the patient was asked to return 2 days later with their self-reading result, followed by blinded reading by a trained nurse (reference).
RESULTS
Of 227 patients, 210 returned for TST reading; 78% interpreted their test correctly: those interpreting it as negative were more likely to be correct (negative predictive value 93%) than those interpreting it as positive (positive predictive value 42%); 10/36 (28%) positive TST results were read as negative by the patient.
CONCLUSIONS
Patients with HIV in low-resource settings can be trained to interpret their own TST. Those interpreting it as positive should return to the clinic within 48–72 h for confirmatory reading and IPT initiation; those with a negative interpretation can return at their next scheduled visit and initiate IPT at that time if appropriate.
The World Health Organization recommends tuberculin skin tests (TSTs) where feasible to identify individuals most likely to benefit from isoniazid preventive therapy (IPT). The requirement for TST reading after 48–72 h by a trained nurse is a barrier to implementation and increases loss to follow-up.
METHODS
Patients with human immunodeficiency virus (HIV) infection were recruited from a primary care clinic in South Africa and trained by a lay counsellor to interpret their own TST. The TST was placed by a nurse, and the patient was asked to return 2 days later with their self-reading result, followed by blinded reading by a trained nurse (reference).
RESULTS
Of 227 patients, 210 returned for TST reading; 78% interpreted their test correctly: those interpreting it as negative were more likely to be correct (negative predictive value 93%) than those interpreting it as positive (positive predictive value 42%); 10/36 (28%) positive TST results were read as negative by the patient.
CONCLUSIONS
Patients with HIV in low-resource settings can be trained to interpret their own TST. Those interpreting it as positive should return to the clinic within 48–72 h for confirmatory reading and IPT initiation; those with a negative interpretation can return at their next scheduled visit and initiate IPT at that time if appropriate.
Journal Article > LetterFull Text
Clin Infect Dis. 2014 April 23; Volume 59 (Issue 3); DOI:10.1093/cid/ciu288
Patten GE, Cox V, Stinson K, Boulle AM, Wilkinson LS
Clin Infect Dis. 2014 April 23; Volume 59 (Issue 3); DOI:10.1093/cid/ciu288
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
Bull World Health Organ. 2015 June 25; Volume 93 (Issue 9); 623-630.; DOI:10.2471/BLT.14.146480
Fajardo E, Metcalf CJ, Piriou E, Gueguen M, Maman D, et al.
Bull World Health Organ. 2015 June 25; Volume 93 (Issue 9); 623-630.; DOI:10.2471/BLT.14.146480
OBJECTIVE
To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Médecins Sans Frontières (MSF) in field projects and identify factors associated with invalid results.
METHODS
We collated 25,616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; if not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with invalid results.
FINDINGS
There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere PimaTM devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3-19.9) and 12.1% (IQR: 7.1-19.2), respectively. The proportion of invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood.
CONCLUSION
The Alere Pima CD4+ analyser generated a high proportion of invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+ T-lymphocyte testing.
To estimate the proportion of invalid results generated by a CD4+ T-lymphocyte analyser used by Médecins Sans Frontières (MSF) in field projects and identify factors associated with invalid results.
METHODS
We collated 25,616 CD4+ T-lymphocyte test results from 39 sites in nine countries for the years 2011 to 2013. Information about the setting, user, training, sampling technique and device repair history were obtained by questionnaire. The analyser performs a series of checks to ensure that all steps of the analysis are completed successfully; if not, an invalid result is reported. We calculated the proportion of invalid results by device and by operator. Regression analyses were used to investigate factors associated with invalid results.
FINDINGS
There were 3354 invalid test results (13.1%) across 39 sites, for 58 Alere PimaTM devices and 180 operators. The median proportion of errors per device and operator was 12.7% (interquartile range, IQR: 10.3-19.9) and 12.1% (IQR: 7.1-19.2), respectively. The proportion of invalid results varied widely by country, setting, user and device. Errors were not associated with settings, user experience or the number of users per device. Tests performed on capillary blood samples were significantly less likely to generate errors compared to venous whole blood.
CONCLUSION
The Alere Pima CD4+ analyser generated a high proportion of invalid test results, across different countries, settings and users. Most error codes could be attributed to the operator, but the exact causes proved difficult to identify. Invalid results need to be factored into the implementation and operational costs of routine CD4+ T-lymphocyte testing.
Journal Article > ResearchFull Text
PLOS One. 2015 November 10; Volume 10 (Issue 11); e0142873.; DOI:10.1371/journal.pone.0142873
Daniels J, Khogali MA, Mohr E, Cox V, Moyo S, et al.
PLOS One. 2015 November 10; Volume 10 (Issue 11); e0142873.; DOI:10.1371/journal.pone.0142873
SETTING
Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.
OBJECTIVE
To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.
DESIGN
A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.
RESULTS
Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4).
CONCLUSIONS
Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.
Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection.
OBJECTIVE
To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes.
DESIGN
A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation.
RESULTS
Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4).
CONCLUSIONS
Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.
Journal Article > ResearchFull Text
Southern African Journal of HIV medicine. 2019 June 11; Volume 20 (Issue 1); 905.; DOI:10.4102/sajhivmed.v20i1.905
Sharp J, Wilkinson LS, Cox V, Cragg C, van Custem G, et al.
Southern African Journal of HIV medicine. 2019 June 11; Volume 20 (Issue 1); 905.; DOI:10.4102/sajhivmed.v20i1.905
BACKGROUND
Eligibility for differentiated antiretroviral therapy (ART) delivery models has to date been limited to low-risk stable patients.
OBJECTIVES
We examined the outcomes of patients who accessed their care and treatment through an ART adherence club (AC), a differentiated ART delivery model, immediately following receiving support to achieve viral suppression after experiencing elevated viral loads (VLs) at a high-burden ART clinic in Khayelitsha, South Africa.
METHODS
Beginning in February 2012, patients with VLs above 400 copies/mL either on first or second-line regimens received a structured intervention developed for patients at risk of treatment failure. Patients who successfully suppressed either on the same regimen or after regimen switch were offered immediate enrolment in an AC facilitated by a lay community health worker. We conducted a retrospective cohort analysis of patients who enrolled in an AC directly after receiving suppression support. We analysed outcomes (retention in care, retention in AC care and viral rebound) using Kaplan–Meier methods with follow-up from October 2012 to June 2015.
RESULTS
A total of 165 patients were enrolled in an AC following suppression (81.8% female, median age 36.2 years). At the closure of the study, 119 patients (72.0%) were virally suppressed and 148 patients (89.0%) were retained in care. Six, 12 and 18 months after AC enrolment, retention in care was estimated at 98.0%, 95.0% and 89.0%, respectively. Viral suppression was estimated to be maintained by 90.0%, 84.0% and 75.0% of patients at 6, 12 and 18 months after AC enrolment, respectively.
CONCLUSION
Our findings suggest that patients who struggled to achieve or maintain viral suppression in routine clinic care can have good retention and viral suppression outcomes in ACs, a differentiated ART delivery model, following suppression support.
Eligibility for differentiated antiretroviral therapy (ART) delivery models has to date been limited to low-risk stable patients.
OBJECTIVES
We examined the outcomes of patients who accessed their care and treatment through an ART adherence club (AC), a differentiated ART delivery model, immediately following receiving support to achieve viral suppression after experiencing elevated viral loads (VLs) at a high-burden ART clinic in Khayelitsha, South Africa.
METHODS
Beginning in February 2012, patients with VLs above 400 copies/mL either on first or second-line regimens received a structured intervention developed for patients at risk of treatment failure. Patients who successfully suppressed either on the same regimen or after regimen switch were offered immediate enrolment in an AC facilitated by a lay community health worker. We conducted a retrospective cohort analysis of patients who enrolled in an AC directly after receiving suppression support. We analysed outcomes (retention in care, retention in AC care and viral rebound) using Kaplan–Meier methods with follow-up from October 2012 to June 2015.
RESULTS
A total of 165 patients were enrolled in an AC following suppression (81.8% female, median age 36.2 years). At the closure of the study, 119 patients (72.0%) were virally suppressed and 148 patients (89.0%) were retained in care. Six, 12 and 18 months after AC enrolment, retention in care was estimated at 98.0%, 95.0% and 89.0%, respectively. Viral suppression was estimated to be maintained by 90.0%, 84.0% and 75.0% of patients at 6, 12 and 18 months after AC enrolment, respectively.
CONCLUSION
Our findings suggest that patients who struggled to achieve or maintain viral suppression in routine clinic care can have good retention and viral suppression outcomes in ACs, a differentiated ART delivery model, following suppression support.
Journal Article > Short ReportFull Text
Southern African Journal of HIV medicine. 2015 April 28; DOI:10.4102/hivmed.v16i1.376
Nelson AM, Maritz J, Giddy J, Frigati L, Rabie H, et al.
Southern African Journal of HIV medicine. 2015 April 28; DOI:10.4102/hivmed.v16i1.376
Journal Article > LetterFull Text
Eur Respir J. 2015 December 1; Volume 46 (Issue 6); DOI:10.1183/13993003.01374-2015
Hughes J, Isaakidis P, Andries A, Mansoor H, Cox V, et al.
Eur Respir J. 2015 December 1; Volume 46 (Issue 6); DOI:10.1183/13993003.01374-2015
Journal Article > ResearchFull Text
Int J Epidemiol. 2016 June 24; DOI:10.1093/ije/dyw097
Schomaker M, Leroy V, Wolfs T, Technau KG, Renner L, et al.
Int J Epidemiol. 2016 June 24; DOI:10.1093/ije/dyw097
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
Journal Article > CommentaryFull Text
Bull World Health Organ. 2015 July 1; Volume 93 (Issue 7); 491-497.; DOI:10.2471/BLT.14.138925
Cox HS, Furin J, Mitnick CD, Daniels C, Cox V, et al.
Bull World Health Organ. 2015 July 1; Volume 93 (Issue 7); 491-497.; DOI:10.2471/BLT.14.138925
Approximately half a million people are thought to develop multidrug-resistant tuberculosis annually. Barely 20% of these people currently receive recommended treatment and only about 10% are successfully treated. Poor access to treatment is probably driving the current epidemic, via ongoing transmission. Treatment scale-up is hampered by current treatment regimens, which are lengthy, expensive, poorly tolerated and difficult to administer in the settings where most patients reside. Although new drugs provide an opportunity to improve treatment regimens, current and planned clinical trials hold little promise for developing regimens that will facilitate prompt treatment scale-up. In this article we argue that clinical trials, while necessary, should be complemented by timely, large-scale, operational research that will provide programmatic data on the use of new drugs and regimens while simultaneously improving access to life-saving treatment. Perceived risks - such as the rapid development of resistance to new drugs - need to be balanced against the high levels of mortality and transmission that will otherwise persist. Doubling access to treatment and increasing treatment success could save approximately a million lives over the next decade.