Effects of national adoption of Treat-All guidelines on pre-ART CD4 testing and viral load monitoring after ART initiation: A regression discontinuity analysis

Background The World Health Organization’s Treat-All guidance recommends CD4 testing prior to antiretroviral treatment (ART) initiation, and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. Methods We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547,837 ART-naïve patients enrolling in HIV care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years) and children (0-9 years) in low/lower-middle income countries (L/LMICs) and high/upper-middle income countries (H/UMICs). Results Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in in H/UMICs, from 90.1 to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients just before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. In H/UMICs, VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. Conclusions While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

Performance of the BD FACSPresto near to patient Analyzer in comparison with representative conventional CD4 instruments in Cameroon.

Background In view of scaling up viral load during the management of HIV in adults and children in resource limited settings, CD4+ T-lymphocyte count still relevant in remote areas where the decentralization of treatment is independent of viral load. Effective clinical management of HIV within these resource-constrained settings depends on affordable and reliable CD4+ T lymphocytes enumeration methods. We have assessed the performance of a BD FACSPresto POC which is a dedicated CD4 enumeration system applicable in remote areas. A comparative analysis was made between the performance of the BD FACSPresto POC and representative flow cytometry instruments present in Cameroon in including FACSCalibur, FACSCount, and PIMA POC from Becton Dickinson and ALERE respectively. All these CD4 enumerations are known to perform more than 5000 CD4 T cells tests per year. Methods: The BD FACSPresto POC CD4+ T cell technology was placed at CIRCB and operated by technician staff. 268 patients aged between 1 to 72 years old were included in the study. Participants were recruited from the Chantal BIYA international reference Center (CIRCB), Centre de Sante Catholique de NKOLODOM, Centre de Sante Catholique de BIKOP and CASS de Nkolndongo – Yaounde respectively. We compared the performance of the BD FACSPresto with three existing CD4 enumeration technologies including FACSCalibur, FACSCount and PIMA capable of performing more than 5000 tests per year. Bland – Altman method and correlation analysis were used to estimate mean bias and 95% limits of agreement and to compare the methods, including analysis by subgroup of participant gestational age. Statistical significance was set at p-value < 0.05 Results: The BD FACSPresto POC CD4 enumeration system showed similar performance with the other CD4+ T lymphocytes enumeration instruments. Strong correlations were obtained between the BD FACSPresto poc system and other single platform methods. Bland–Altman plots showed interchangeability between two machines mean bias BD-FACSPresto vs PIMA= -126,522(-161,221 to -91,822) BD-FACSPresto vs FACSCount= -38,708 (-58,935 to -18,482) and FACSPresto vs FACSCALIBUR= 0,791(-11,908 to 13,491). Mean difference with Absolute CD4+ T-lymphocyte values obtained from the BD FACSPresto system correlated well with PIMA, FACSCount, and FACSCalibur method with R² equal to 0.88, 0.92 and 0.968 respectively with P < 0.001 for all. The mean comparison between values obtained from BD FACSPresto with PIMA, FACSCount, and FACSCalibur using paired T test give P=0.17, P=0.5 and P=0.6 respectively meaning that there is no significant differences between values obtained with BD FACSPresto and PIMA, FACSCount or FACSCalibur CD4 enumeration machines. Further analysis revealed close agreement between all the three instruments with no significant difference between the four equipment with different methods of analysis (P=0.91) Conclusion: This BD-FACSPresto POC system is a simple, robust and reliable system for enumeration of absolute and CD4+ T-lymphocytes percentages especially in remote areas with limited resources. Having a single BD-FACSPresto POC system which is easy to use, should reduce the cost and thus increase and improved access to CD4 testing for HIV infected patients in remote areas of resource-constrained countries. BD-FACSPresto POC CD4 will enable reduction in patient wait time and improve the overall quality of ART service count and may improve test access in remote areas. This technology can allow for greater decentralization and wider access to CD4 testing in areas where viral load is not possible during ART

Performance of the BD FACSPresto near to patient Analyzer in comparison with representative conventional CD4 instruments in Cameroon.

Background: In the context of scaling the viral load in resource limited settings, following HIV infected patient’s adults and children with CD4+ T-lymphocyte count still very important in settings where the decentralization of treatment still has some challenges. Effective HIV monitoring in these resource-constrained settings needs affordable and reliable CD4+ T lymphocytes enumeration methods. We investigated the validity of a BD FACSPresto POC which is a dedicated system for enumeration that uses immunofluorescent technologies. In this study, we have assessed the correlation between most representative flow cytometry instruments present in Cameroon with more than 5000 CD4 T cells tests per year including FACSCalibur, FACSCount, and PIMA POC from Becton Dickinson and ALERE respectively. Methods: 268 patients aged from 1 to 72 years old were enrolled and included in the study. The BD FACSPresto POC CD4+ T cell technology was placed at CIRCB and operated by technician staff. HIV infected patients were from Chantal BIYA international reference Center (CIRCB), Centre de Sante Catholique de NKOLODOM, Centre de Sante Catholique de BIKOP and CASS de Nkolndongo – Yaounde We compared the accuracy of the BD FACSPresto and three existing reference technologies with more than 5000 tests per year like FACSCalibur, FACSCount and PIMA according to the number of CD4 test done per year and their repartition in the country. Bland – Altman method and correlation analysis were used to estimate mean bias and 95% limits of agreement and to compare the methods, including analysis by subgroup of participant gestational age. Statistical significance was set at p-value < 0.05Results: The BD FACSPresto POC system has excellent precision, accuracy and linearity for CD4+ T lymphocytes enumeration. Good correlations were obtained between the BD FACSPresto poc system and other single platform methods. Bland–Altman plots showed interchangeability between two machines mean bias BD-FACSPresto vs PIMA= -126,522(-161,221 to -91,822) BD-FACSPresto vs FACSCount= -38,708 (-58,935 to -18,482) and FACSPresto vs FACSCALIBUR= 0,791(-11,908 to 13,491). Mean difference with Absolute CD4+ T-lymphocyte values obtained from the BD FACSPresto system correlated well with PIMA, FACSCount, and FACSCalibur method with R² equal to 0.88, 0.92 and 0.968 respectively with P < 0.001 for all. The mean comparison between values obtained from BD FACSPresto with PIMA, FACSCount, and FACSCalibur using paired T test give P=0.17, P=0.5 and P=0.6 respectively meaning that there is no significant differences between values obtained with BD FACSPresto and PIMA, FACSCount or FACSCalibur CD4 enumeration machines. Further analysis revealed close agreement between all the three instruments with no significant difference between the forth methods (P=0.91) Conclusion: This BD-FACSPresto POC system is a simple, robust and reliable system for enumeration of absolute and percentage of CD4+ T-lymphocytes especially suitable for remote areas with limited resources. Having one BD-FACSPresto POC system easy to use, should reduce the cost and thus increase and improved access to CD4 testing for HIV infected patients in resource-constrained countries. BD-FACSPresto POC CD4 will enable reduction in patient time and improve the overall quality of ART service count and may improve test access in remote areas. This technology can allow for greater decentralization and wider access to CD4 testing and ART

Reduction in Baseline CD4 Count Testing Following Human Immunodeficiency Virus “Treat All” Adoption in Uganda

Baseline CD4 testing rates declined from 73% to 21% between 2013 and 2018 with adoption of “Treat All” in Uganda. Advanced human immunodeficiency virus (HIV) disease (CD4 count &lt; 200 cells/µL) remained common (24% of those tested in 2018, 83% of whom had World Health Organization stage I/II disease). Despite frequent presentation with advanced HIV disease, CD4 testing has declined dramatically.

Trends in CD4 and viral load testing 2005 to 2018: Multi-cohort study of people living with HIV in Southern Africa

IntroductionWHO recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.MethodsWe analysed data from 14 HIV treatment programs with over 300 clinics in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in years 2005-2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3) or failing to suppress viral replication (>1000 HIV-RNA copies/ml) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex.ResultsAmong 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017. The percentage starting with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018. VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested but fewer than 2% were tested in the other four countries. The probability of having a CD4 cell count at ART start declined by 14% each year (odds ratio [OR] 0.86; 95% CI 0.86-0.86); the probability of advanced HIV disease declined by 20% per year (OR 0.80; 95% CI 0.80-0.81). The increase in VL testing after ART start was only modest (OR 1.06; 95% CI 1.05-1.06) and there was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99-1.01).ConclusionsCD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.

Cost-effectiveness of reflex laboratory-based cryptococcal antigen screening for the prevention and treatment of cryptococcal meningitis in Botswana

Background: Cryptococcal antigen (CrAg) screening for antiretroviral therapy (ART)-naïve adults with advanced HIV/AIDS can reduce the incidence of cryptococcal meningitis (CM) and all-cause mortality. We modeled the cost-effectiveness of laboratory-based “reflex” CrAg screening for ART-naïve CrAg-positive patients with CD4<100 cells/µL (those currently targeted in guidelines) and ART-experienced CrAg-positive patients with CD4<100 cells/µL (who make up an increasingly large proportion of individuals with advanced HIV/AIDS). Methods: A decision analytic model was developed to evaluate CrAg screening and treatment based on local CD4 count and CrAg prevalence data, and realistic assumptions regarding programmatic implementation of the CrAg screening intervention. We modeled the number of CrAg tests performed, the number of CrAg positives stratified by prior ART experience, the proportion of patients started on pre-emptive antifungal treatment, and the number of incident CM cases and CM-related deaths. Screening and treatment costs were evaluated, and cost per death or disability-adjusted life year (DALY) averted estimated. Results: We estimated that of 650,000 samples undergoing CD4 testing annually in Botswana, 16,364 would have a CD4<100 cells/µL and receive a CrAg test, with 70% of patients ART-experienced at the time of screening. Under base model assumptions, CrAg screening and pre-emptive treatment restricted to ART-naïve patients with a CD4<100 cells/µL prevented 20% (39/196) of CM-related deaths in patients undergoing CD4 testing at a cost of US$2 per DALY averted. Expansion of preemptive treatment to include ART-experienced patients with a CD4<100 cells/µL resulted in 55 additional deaths averted (a total of 48% [94/196]) and was cost-saving compared to no screening. Findings were robust across a range of model assumptions. Conclusions: Reflex laboratory-based CrAg screening for patients with CD4<100 cells/µL is a cost-effective strategy in Botswana, even in the context of a relatively low proportion of advanced HIV/AIDS in the overall HIV-infected population, the majority of whom are ART-experienced.