Immunologic Response and HIV Progression Following HAART
Immunologic Response and HIV Progression Following HAART
Objectives Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes.
Methods Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (≥3, 1–2 or <1) or CD4 (≥3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively.
Results Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001).
Conclusion Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.
Highly active antiretroviral therapy (HAART) suppresses HIV viral load (VL) resulting in enhanced patient immune function and reduced risk of opportunistic infections and death. Disparities remain in patient access to antiretrovirals (ARVs), however, the challenges of treatment coverage and health system capacity are being progressively addressed. As a result, more HIV-infected patients in developing and transitional economies have the opportunities of decreased morbidity and longer survival as have been observed in developed economies.
Predictive biomarkers of disease progression are HIV RNA in plasma (VL) and CD4 cell count (immune function). HIV RNA informs knowledge of trends in viral replication and gives advance notice of non-adherence, treatment regimen failure and HIV drug resistance (HIVDR). CD4 cell counts provide quantitative measures of immunocompetence and current clinical status. Furthermore, international patient management guidelines recommend periodic collection of HIV RNA and CD4 cell counts to determine indications for treatment and the monitoring of therapeutic response.
Still, in developing countries access to disease staging diagnostics has lagged considerably behind the availability of anti-HIV medications. Consequently, monitoring of patient status via surrogate markers, thereby identifying optimal therapy initiation periods and when treatment should be changed, is not available in resource-limited settings at a level comparable to that found in developed economies. Plasma VL commercial assay kits and CD4 reagents remain expensive. Assays require dedicated space and equipment and infrastructure costs are prohibitive. Further, the lack of physical resources, such as uninterrupted electricity and water, and the cost and availability of maintenance impact upon whether valid results of patient prognostic status are obtained even when infrastructure is in place. Currently, there is little information on how the lack of economic and, particularly, diagnostic resourcing affects patient health outcomes. Therefore, our objective was to determine whether clinical resourcing, measured as country income and site-reported frequencies of CD4 and VL diagnostic testing, impacted on patient treatment outcomes.
Abstract and Introduction
Abstract
Objectives Surrogate markers of HIV disease progression are HIV RNA in plasma viral load (VL) and CD4 cell count (immune function). Despite improved international access to antiretrovirals, surrogate marker diagnostics are not routinely available in resource-limited settings. Therefore, the objective was to assess effects of economic and diagnostic resourcing on patient treatment outcomes.
Methods Analyses were based on 2333 patients initiating highly active antiretroviral therapy (HAART) from 2000 onwards. Sites were categorized by World Bank country income criteria (high/low) and annual frequency of VL (≥3, 1–2 or <1) or CD4 (≥3 or <3) testing. Endpoints were time to AIDS/death and change in CD4 cell count and VL suppression (<400 HIV-1 RNA copies/mL) at 12 months. Demographics, Centers for Disease Control and Prevention (CDC) classification, baseline VL/CD4 cell counts, hepatitis B/C coinfections and HAART regimen were covariates. Time to AIDS/death was analysed by proportional hazards models. CD4 and VL endpoints were analysed using linear and logistic regression, respectively.
Results Increased disease progression was associated with site-reported VL testing less than once per year [hazard ratio (HR)=1.4; P=0.032], severely symptomatic HIV infection (HR=1.4; P=0.003) and hepatitis C virus coinfection (HR=1.8; P=0.011). A total of 1120 patients (48.2%) had change in CD4 cell count data. Smaller increases were associated with older age (P<0.001) and 'Other' HIV source exposures, including injecting drug use and blood products (P=0.043). A total of 785 patients (33.7%) contributed to the VL suppression analyses. Patients from sites with VL testing less than once per year [odds ratio (OR)=0.30; P<0.001] and reporting 'Other' HIV exposures experienced reduced suppression (OR=0.28; P<0.001).
Conclusion Low measures of site resourcing were associated with less favourable patient outcomes, including a 35% increase in disease progression in patients from sites with VL testing less than once per year.
Introduction
Highly active antiretroviral therapy (HAART) suppresses HIV viral load (VL) resulting in enhanced patient immune function and reduced risk of opportunistic infections and death. Disparities remain in patient access to antiretrovirals (ARVs), however, the challenges of treatment coverage and health system capacity are being progressively addressed. As a result, more HIV-infected patients in developing and transitional economies have the opportunities of decreased morbidity and longer survival as have been observed in developed economies.
Predictive biomarkers of disease progression are HIV RNA in plasma (VL) and CD4 cell count (immune function). HIV RNA informs knowledge of trends in viral replication and gives advance notice of non-adherence, treatment regimen failure and HIV drug resistance (HIVDR). CD4 cell counts provide quantitative measures of immunocompetence and current clinical status. Furthermore, international patient management guidelines recommend periodic collection of HIV RNA and CD4 cell counts to determine indications for treatment and the monitoring of therapeutic response.
Still, in developing countries access to disease staging diagnostics has lagged considerably behind the availability of anti-HIV medications. Consequently, monitoring of patient status via surrogate markers, thereby identifying optimal therapy initiation periods and when treatment should be changed, is not available in resource-limited settings at a level comparable to that found in developed economies. Plasma VL commercial assay kits and CD4 reagents remain expensive. Assays require dedicated space and equipment and infrastructure costs are prohibitive. Further, the lack of physical resources, such as uninterrupted electricity and water, and the cost and availability of maintenance impact upon whether valid results of patient prognostic status are obtained even when infrastructure is in place. Currently, there is little information on how the lack of economic and, particularly, diagnostic resourcing affects patient health outcomes. Therefore, our objective was to determine whether clinical resourcing, measured as country income and site-reported frequencies of CD4 and VL diagnostic testing, impacted on patient treatment outcomes.
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