Journal Article > ResearchFull Text
PLOS One. 23 February 2012; Volume 7 (Issue 2); e31706.; DOI:10.1371/journal.pone.0031706
Henriques J, Pujades M, McGuire M, Szumilin E, Iwaz J, et al.
PLOS One. 23 February 2012; Volume 7 (Issue 2); e31706.; DOI:10.1371/journal.pone.0031706
OBJECTIVE
The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses.
METHODS
We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis.
RESULTS
Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76-1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61-2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17-1.66 vs. 1.29 to 1.34).
CONCLUSIONS
In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.
The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses.
METHODS
We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis.
RESULTS
Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76-1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61-2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17-1.66 vs. 1.29 to 1.34).
CONCLUSIONS
In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.
Journal Article > ResearchFull Text
J Clin Microbiol. 16 July 2014; Volume 52 (Issue 9); DOI:10.1128/JCM.00593-14
Ritchie AV, Ushiro-Lumb I, Edemaga D, Joshi HA, De Ruiter A, et al.
J Clin Microbiol. 16 July 2014; Volume 52 (Issue 9); DOI:10.1128/JCM.00593-14
Routine viral load (VL) testing of HIV-infected individuals on antiretroviral therapy (ART) is used to monitor treatment efficacy. However, due to logistical challenges, implementation of VL has been difficult in resource-limited settings. The aim of this study was to evaluate the performance of the SAMBA Semi-Q Test in London, Malawi, and Uganda. The SAMBA HIV-1 Semi-Q Test can distinguish between patients with VL above or below 1000 copies/ml. The SAMBA Semi-Q was validated with diluted clinical samples and blinded plasma samples collected from HIV-1-positive individuals. SAMBA Semi-Q results were compared with results from the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0. Testing of 96 2-10 fold dilutions of four samples containing HIV-1 subtype C as well as 488 samples from patients in the United Kingdom, Malawi, and Uganda, respectively, yielded an overall accuracy for SAMBA Semi-Q of 99% (95% CI 93.8 - 99.9%) and 96.9% (95% CI 94.9 - 98.3%) respectively compared to Roche. Analysis of VL data from patients in Malawi and Uganda showed that the SAMBA cut-off of 1000 copies/ml appropriately distinguished treated from untreated individuals. Furthermore, analysis of the viral load of 232 patients on ART in Malawi and Uganda revealed similar patterns for virological control defined as either <1000 copies/ml (SAMBA cut-off) or <5000 copies/ml (WHO 2010 criterion). This study suggests that SAMBA Semi-Q has adequate concurrency with the gold standard measurements for viral load measurement. This test can allow VL monitoring of patients on ART at the point of care in resource-limited settings.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 June 2010; Volume 15; DOI:10.1111/j.1365-3156.2010.02504.x
McGuire M, Munyenyembe T, Szumilin E, Heinzelmann A, Le Paih M, et al.
Trop Med Int Health. 1 June 2010; Volume 15; DOI:10.1111/j.1365-3156.2010.02504.x
OBJECTIVES: To ascertain the outcome of pre-Antiretroviral therapy (ART) and ART patients defaulting from care and investigate reasons for defaulting. METHODS: Patients defaulting from HIV care in Chiradzulu between July 2004 and September 2007 were traced at last known home address. Deaths and moves were recorded, and patients found alive were interviewed. Defaulting was defined as missed last appointment by more than 1 month among patients of unknown vital status. RESULTS: A total of 1637 individuals were traced (54%-88% of eligible), 981 pre-ART and 656 ART patients. Of 694 pre-ART patients found, 49% had died (51% of adults and 38% of children), a median of 47 days after defaulting, and 14% had moved away. Of 451 ART patients found, 54% had died (54% of adults and 50% of children), a median of 52 days after defaulting, and 20% had moved away. Overall, 221 patients were interviewed (90% of those found alive), 42% had worked outside the district in the previous year; 49% of pre-ART and 19% of ART patients had not disclosed their HIV status to other household members. Main reasons for defaulting were stigma (43%), care dissatisfaction (34%), improved health (28%) and for ART discontinuation, poor understanding of disease or treatment (56%) and drug side effects (42%). CONCLUSION: This study in a rural African HIV programme reveals the dynamics related to health service access and use, and it provides information to correct programme mortality estimates for adults and children.
Journal Article > ResearchFull Text
AIDS. 17 July 2012; Volume 26 (Issue 11); 1393-8.; DOI:10.1097/QAD.0b013e328352d054
Maman D, Pujades-Rodriguez M, Nicholas S, McGuire M, Szumilin E, et al.
AIDS. 17 July 2012; Volume 26 (Issue 11); 1393-8.; DOI:10.1097/QAD.0b013e328352d054
OBJECTIVE
We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières.
DESIGN
Multicentric retrospective cohort study.
METHODS
All antiretroviral therapy (ART) naive adults (>15 years) who initiated therapy between March 2001 and November 2010 and receiving therapy for 9 months or more were included. We described the evolution of mortality over time. Mixed Poisson models were used to assess the effect of updated CD4 cell counts and other potential risk factors on mortality.
FINDINGS
A total of 24 037 patients, of which 68% were women, contributed 69 516.2 person-years of follow-up. At ART initiation, 5718 patients (23.7%) were classified as WHO clinical stage 4, 1587 (6.6%) had a BMI below 16 kg/m and 2568 (10.7%) had CD4 cell count below 50 cells/μl. A total of 568 (2.4%) deaths were recorded during the study period. In the CD4 response categories 500 cells/μl or more, 350-499, 200-349, 50-199 cells/μl and less than 50 cells/μl, unadjusted mortality rates were 0.36; 0.58; 0.88; 1.91 and 7.43 per 100 person-years, respectively. In multivariate analysis, higher mortality was observed in patients with CD4 response levels 350-499 cells/μl [adjusted hazard ratio (aHR) 1.70, 95% confidence interval (CI) 1.26-2.30] and for those between 200-349 (aHR 2.56; 95% CI 1.93-3.38), compared to those with 500 cells/μl or more.
INTERPRETATION
The observed higher survival of patients with a CD4 response to ART higher than 500 cells/μl supports the need of further research to evaluate the individual benefit of initiating ART at higher CD4 levels in sub-Saharan Africa.
We investigated the association between immune response and mortality in four HIV African programs supported by Médecins Sans Frontières.
DESIGN
Multicentric retrospective cohort study.
METHODS
All antiretroviral therapy (ART) naive adults (>15 years) who initiated therapy between March 2001 and November 2010 and receiving therapy for 9 months or more were included. We described the evolution of mortality over time. Mixed Poisson models were used to assess the effect of updated CD4 cell counts and other potential risk factors on mortality.
FINDINGS
A total of 24 037 patients, of which 68% were women, contributed 69 516.2 person-years of follow-up. At ART initiation, 5718 patients (23.7%) were classified as WHO clinical stage 4, 1587 (6.6%) had a BMI below 16 kg/m and 2568 (10.7%) had CD4 cell count below 50 cells/μl. A total of 568 (2.4%) deaths were recorded during the study period. In the CD4 response categories 500 cells/μl or more, 350-499, 200-349, 50-199 cells/μl and less than 50 cells/μl, unadjusted mortality rates were 0.36; 0.58; 0.88; 1.91 and 7.43 per 100 person-years, respectively. In multivariate analysis, higher mortality was observed in patients with CD4 response levels 350-499 cells/μl [adjusted hazard ratio (aHR) 1.70, 95% confidence interval (CI) 1.26-2.30] and for those between 200-349 (aHR 2.56; 95% CI 1.93-3.38), compared to those with 500 cells/μl or more.
INTERPRETATION
The observed higher survival of patients with a CD4 response to ART higher than 500 cells/μl supports the need of further research to evaluate the individual benefit of initiating ART at higher CD4 levels in sub-Saharan Africa.
Journal Article > ResearchFull Text
PLOS One. 16 September 2013; Volume 8 (Issue 9); DOI:10.1371/journal.pone.0074090
McGuire M, Farhat JB, Pedrono G, Szumilin E, Heinzelmann A, et al.
PLOS One. 16 September 2013; Volume 8 (Issue 9); DOI:10.1371/journal.pone.0074090
Background: Expanding access to antiretroviral therapy (ART) in sub-Saharan Africa requires implementation of alternative care delivery models to traditional physician-centered approaches. This longitudinal analysis compares outcomes of patients initiated on antiretroviral therapy (ART) by non-physician and physician providers. Methods: Adults (≥15 years) initiating ART between September 2007 and March 2010, and with >1 follow-up visit were included and classified according to the proportion of clinical visits performed by nurses or by clinical officers(≥80% of visits). Multivariable Poisson models were used to compare 2-year program attrition (mortality and lost to follow-up) and mortality by type of provider. In sensitivity analyses only patients with less severe disease were included. Results: A total of 10,112 patients contributed 14,012 person-years to the analysis: 3386 (33.5%) in the clinical officer group, 1901 (18.8%) in the nurse care group and 4825 (47.7%) in the mixed care group. Overall 2-year program retention was 81.8%. Attrition was lower in the mixed care and higher in the clinical officer group, compared to the nurse group (adjusted incidence rate ratio [aIRR]=0.54, 95%CI 0.45-0.65; and aIRR=3.03, 95%CI 2.56-3.59,respectively). While patients initiated on ART by clinical officers in the mixed care group had lower attrition(aIRR=0.36, 95%CI 0.29-0.44) than those in the overall nurse care group; no differences in attrition were found between patients initiated on ART by nurses in the mixed care group and those included in the nurse group (aIRR=1.18, 95%CI 0.95-1.47). Two-year mortality estimates were aIRR=0.72, 95%CI 0.49-1.09 and aIRR=5.04,95%CI 3.56-7.15, respectively. Slightly higher estimates were observed when analyses were restricted to patients with less severe disease. Conclusion: The findings of this study support the use of a mixed care model with well trained and regularly supervised nurses and medical assistants to provide HIV care in countries with high HIV prevalence.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 September 2011; Volume 16 (Issue 12); DOI:10.1111/j.1365-3156.2011.02874.x
Kanapathipillai R, McGuire M, Mogha R, Szumilin E, Heinzelmann A, et al.
Trop Med Int Health. 1 September 2011; Volume 16 (Issue 12); DOI:10.1111/j.1365-3156.2011.02874.x
Objective Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa. Methods Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated. Results Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria. Conclusions Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries.