Journal Article > ResearchFull Text
Trop Med Int Health. 2016 March 6; Volume 21 (Issue 5); 603-609.; DOI:10.1111/tmi.12688
Kosack CS, Nick S
Trop Med Int Health. 2016 March 6; Volume 21 (Issue 5); 603-609.; DOI:10.1111/tmi.12688
OBJECTIVE
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
METHODS
Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany.
RESULTS
Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9).
CONCLUSION
This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.
To evaluate the diagnostic accuracy of the OraQuick HCV rapid antibody test from OraSure and the Multisure HCV antibody assay from MP Biomedicals.
METHODS
Five seropanels from patients, intravenous drug users and blood donors with and without HCV infection were used on the two rapid immunochromatographic tests. Sensitivity, specificity and predictive values were calculated. In addition, seropanels from 10 seroconverters were used to assess early identification of HCV infection. The study was undertaken in a laboratory at Paul Ehrlich Institute in Germany.
RESULTS
Panel 1 contained of 55 positive and 25 negative samples. The OraQuick HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 100% (95% CI: 86.3-100). The Multisure HCV test had a sensitivity of 100% (95% CI: 93.5-100) and a specificity of 96% (95% CI: 79.6-99.9). Panel 2 consisted of 193 pre-characterised anti-HCV-positive patient samples. The OraQuick HCV test identified 191 samples correctly and the Multisure HCV 192. The sensitivity was 99.0% (95% CI: 96.3-99.9) for the OraQuick HCV test and 99.5% (95% CI: 97.1-100) for the Multisure HCV test. Panel 3 was composed of seroconversion samples of 10 patients. The OraQuick HCV test detected all of these 10 infections while the Multisure HCV test detected six and was indeterminate on 2. Panel 4 included 53 anti-HCV negative blood samples from blood donors. Both tests correctly identified all 53. Panel 5 consisted of 26 samples of HCV/HIV co-infected patients. The sensitivity of the OraQuick HCV test was 65.2% (95% CI: 42.8-82.8) after 20 min and 73.9% (95% CI: 51.3-88.9) after 40 min of incubation. The Multisure HCV test had a sensitivity of 96.2% (95% CI: 80.4-99.9).
CONCLUSION
This evaluation revealed good sensitivity for both rapid screening assays. The detection of seroconverters, however, was lower in the MutiSure HCV test. Therefore the MultiSure test should be used with hesitation in high incidence settings. The OraQuick gave HCV false-negative results in almost 25% of the HIV-positive sera. Therefore may the OraQuick be less suited in HIV prevalent areas.
Journal Article > ResearchFull Text
Public Health Action. 2022 June 21; Volume 12 (Issue 2); 96-101.; DOI:10.5588/pha.22.0002
Kirakosyan O, Melikyan N, Falcao J, Khachatryan N, Atshemyan H, et al.
Public Health Action. 2022 June 21; Volume 12 (Issue 2); 96-101.; DOI:10.5588/pha.22.0002
BACKGROUND
Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients.
METHODS
We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment.
RESULTS
The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden.
CONCLUSION
Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.
Direct-acting antivirals (DAAs) are not widely used for patients with chronic hepatitis C virus (HCV) infection and multidrug- or rifampicin-resistant TB (MDR/RR-TB). We describe the implementation aspects of a new integrated model of care in Armenia and the perceptions of the healthcare staff and patients.
METHODS
We used qualitative methods, including a desktop review and semi-structured individual interviews with healthcare staff and with patients receiving HCV and MDR/RR-TB treatment.
RESULTS
The new integrated model resulted in simplified management of HCV and MDR/RR-TB at public TB facilities. Training on HCV was provided for TB clinic staff. All MDR/RR-TB patients were systematically offered HCV testing and those diagnosed with HCV, offered treatment with DAAs. Treatment monitoring was performed by TB staff in coordination with a hepatologist. The staff interviewed had a positive opinion of the new model. They suggested that additional training should be provided. Most patients were fully satisfied with the care received. Some were concerned about the increased pill burden.
CONCLUSION
Integrating HCV treatment into MDR/ RR-TB care was feasible and appreciated by patients and staff. This new model facilitated HCV diagnosis and treatment among people with MDR/RR-TB. Our results encourage piloting this model in other settings.
Journal Article > ResearchFull Text
J Viral Hepat. 2020 November 4; Volume 28 (Issue 2); 268-278.; DOI:10.1111/jvh.13422
Mafirakureva N, Lim AG, Khalid GG, Aslam K, Campbell L, et al.
J Viral Hepat. 2020 November 4; Volume 28 (Issue 2); 268-278.; DOI:10.1111/jvh.13422
Despite the availability of effective direct-acting antiviral (DAA) treatments for Hepatitis C virus (HCV) infection, many people remain undiagnosed and untreated. We assessed the cost-effectiveness of a Médecins Sans Frontières (MSF) HCV screening and treatment programme within a primary health clinic in Karachi, Pakistan. A health state transition Markov model was developed to estimate the cost-effectiveness of the MSF programme. Programme cost and outcome data were analysed retrospectively. The incremental cost-effectiveness ratio (ICER) was calculated in terms of incremental cost (2016 US$) per disability-adjusted life year (DALY) averted from the provider's perspective over a lifetime horizon. The robustness of the model was evaluated using deterministic and probabilistic sensitivity analyses (PSA). The ICER for implementing testing and treatment compared to no programme was US$450/DALY averted, with 100% of PSA runs falling below the per capita Gross Domestic Product threshold for cost-effective interventions for Pakistan (US$1,422). The ICER increased to US$532/DALY averted assuming national HCV seroprevalence (5.5% versus 33% observed in the intervention). If the cost of liver disease care was included (adapted from resource use data from Cambodia which has similar GDP to Pakistan), the ICER dropped to US$148/DALY, while it became cost-saving if a recently negotiated reduced drug cost of $75/treatment course was assumed (versus $282 in base-case) in addition to cost of liver disease care. In conclusion, screening and DAA treatment for HCV infection are expected to be highly cost-effective in Pakistan, supporting the expansion of similar screening and treatment programmes across Pakistan.
Journal Article > ResearchAbstract Only
J Viral Hepat. 2020 May 2; Volume 27 (Issue 9); 886-895.; DOI:10.1111/jvh.13311
Zhang M, O'Keefe D, Iwamoto M, Sann K, Kien A, et al.
J Viral Hepat. 2020 May 2; Volume 27 (Issue 9); 886-895.; DOI:10.1111/jvh.13311
Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF+DCV) facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières(MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF+DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF+DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post-treatment (SVR12) according to a modified intention to treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and non-serious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n=8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF+DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.
Journal Article > ResearchFull Text
Liver Int. 2020 May 31; Volume 40 (Issue 10); 2356-2366.; DOI:10.1111/liv.14550
Walker JG, Mafirakureva N, Iwamoto M, Campbell L, Kim CS, et al.
Liver Int. 2020 May 31; Volume 40 (Issue 10); 2356-2366.; DOI:10.1111/liv.14550
BACKGROUND & AIMS
In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention.
METHODS
Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY).
RESULTS
The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters.
CONCLUSIONS
The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings.
In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention.
METHODS
Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY).
RESULTS
The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters.
CONCLUSIONS
The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings.
Journal Article > ResearchFull Text
Health Sci Rep. 2023 February 17; Volume 6 (Issue 2); e1119.; DOI:doi.org/10.1002/hsr2.1119
Swe TM, Johnson DC, Mar HT, Thit P, Homan T, et al.
Health Sci Rep. 2023 February 17; Volume 6 (Issue 2); e1119.; DOI:doi.org/10.1002/hsr2.1119
BACKGROUND AND AIMS
In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar.
METHODS
HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure.
RESULTS
About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up.
CONCLUSION
The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.
In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar.
METHODS
HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure.
RESULTS
About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up.
CONCLUSION
The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.
Conference Material > Poster
Ashakin KA, Hadiuzzaman M, Firuz W, Rahman A, Ben-Farhat J, et al.
Epicentre Scientific Day 2024. 2024 May 23
Journal Article > ResearchFull Text
Sci Rep. 2019 May 13; Volume 9 (Issue 1); 7314.; DOI:10.1038/s41598-019-43785-4
Nouhin J, Iwamoto M, Prak S, Doussett JP, Phon K, et al.
Sci Rep. 2019 May 13; Volume 9 (Issue 1); 7314.; DOI:10.1038/s41598-019-43785-4
In Cambodia, little epidemiological data of hepatitis C virus (HCV) is available. All previous studies were limited to only small or specific populations. In the present study, we performed a characterization of HCV genetic diversity based on demography, clinical data, and phylogenetic analysis of HCV non-structural 5B (NS5B) sequences belonging to a large cohort of patients (n = 3,133) coming from majority part of Cambodia between September 2016 and December 2017. The phylogenetic analysis revealed that HCV genotype 1 and 6 were the most predominant and sharing equal proportions (46%). The remaining genotypes were genotype 2 (4.3%) and unclassified variants (3.6%). Among genotype 1, subtype 1b was the most prevalent subtype accounting for 94%. Within genotype 6, we observed a high degree of diversity and the most common viral subtypes were 6e (44%) and 6r (23%). This characteristic points to the longstanding history of HCV in Cambodia. Geographic specificity of viral genotype was not observed. Risks of HCV infection were mainly associated with experience of an invasive medical procedure (64.7%), having partner with HCV (19.5%), and blood transfusion (9.9%). In addition, all of these factors were comparable among different HCV genotypes. All these features define the specificity of HCV epidemiology in Cambodia.
Journal Article > ResearchFull Text
Pan Afr Med J. 2017 December 31; Volume 30; 44.; DOI:10.11604/pamj.2018.30.44.14663
Yambasu EE, Reid AJ, Owiti P, Manzi M, Sia Murray MJ, et al.
Pan Afr Med J. 2017 December 31; Volume 30; 44.; DOI:10.11604/pamj.2018.30.44.14663
INTRODUCTION
Transmissible blood-borne infections are a serious threat to blood transfusion safety in West African countries; and yet blood remains a key therapeutic product in the clinical management of patients. Sierra Leone screens blood donors for blood-borne infections but has not implemented prevention of mother-to-child transmission for hepatitis B. This study aimed to describe the overall prevalence of hepatitis B and C, HIV and syphilis among blood donors in Sierra Leone in 2016 and to compare the differences between volunteer versus family replacement donors, as well as urban versus rural donors.
METHODS
Retrospective, cross-sectional study from January-December 2016 in five blood bank laboratories across the country. Routinely-collected programme data were analyzed; blood donors were tested with rapid diagnostic tests-HBsAg for HBV, anti-HCV antibody for HCV, antibodies HIV1&2 for HIV and TPHA for syphilis.
RESULTS
There were 16807 blood samples analysed, with 80% from males; 2285 (13.6%) tested positive for at least one of the four pathogens. Overall prevalence was: 9.7% hepatitis B; 1.0% hepatitis C; 2.8% HIV; 0.8% syphilis. Prevalence was higher among samples from rural blood banks, the difference most marked for hepatitis C. The proportion of voluntary donors was 12%. Family replacement donors had a higher prevalence of hepatitis B, C and HIV than volunteers.
CONCLUSION
A high prevalence of blood-borne pathogens, particularly hepatitis B, was revealed in Sierra Leone blood donors. The study suggests the country should implement the prevention of mother-to-child transmission of hepatitis B and push to recruit more volunteer, non-remunerated blood donors.
Transmissible blood-borne infections are a serious threat to blood transfusion safety in West African countries; and yet blood remains a key therapeutic product in the clinical management of patients. Sierra Leone screens blood donors for blood-borne infections but has not implemented prevention of mother-to-child transmission for hepatitis B. This study aimed to describe the overall prevalence of hepatitis B and C, HIV and syphilis among blood donors in Sierra Leone in 2016 and to compare the differences between volunteer versus family replacement donors, as well as urban versus rural donors.
METHODS
Retrospective, cross-sectional study from January-December 2016 in five blood bank laboratories across the country. Routinely-collected programme data were analyzed; blood donors were tested with rapid diagnostic tests-HBsAg for HBV, anti-HCV antibody for HCV, antibodies HIV1&2 for HIV and TPHA for syphilis.
RESULTS
There were 16807 blood samples analysed, with 80% from males; 2285 (13.6%) tested positive for at least one of the four pathogens. Overall prevalence was: 9.7% hepatitis B; 1.0% hepatitis C; 2.8% HIV; 0.8% syphilis. Prevalence was higher among samples from rural blood banks, the difference most marked for hepatitis C. The proportion of voluntary donors was 12%. Family replacement donors had a higher prevalence of hepatitis B, C and HIV than volunteers.
CONCLUSION
A high prevalence of blood-borne pathogens, particularly hepatitis B, was revealed in Sierra Leone blood donors. The study suggests the country should implement the prevention of mother-to-child transmission of hepatitis B and push to recruit more volunteer, non-remunerated blood donors.
Journal Article > ResearchFull Text
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Morgan JR, Marsh E, Savinkina A, Shilton S, Shadaker S, et al.
J Viral Hepat. 2022 March 12; Online ahead of print; DOI: 10.1111/jvh.13672
Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12-weeks post-treatment (SVR12). We assembled a global dataset of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique), and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th , 95th, 97th, and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5,973 cases of detectable viremia at SVR12 from the combined dataset. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viremia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR=1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure