Antiretroviral Therapy In Low-income Countries Research Articles

Improved life expectancy of people living with HIV: who is left behind?

Improved life expectancy of people living with HIV: who is left behind?

A Model for Reduced HIV-1 Viral Load Monitoring in Resource-Limited Settings

Viral load monitoring of antiretroviral therapy in low-income countries is rarely used because of high costs. Reducing the frequency of monitoring may make it financially feasible. We modeled three testing schemes: reduced viral load monitoring (RVLM) with CD4 count at baseline and viral load testing at 6, 36, and 60 months; United States Department of Health and Human Services (US DHHS) Treatment Guidelines; and World Health Organization (WHO) Guidelines using a cohort of 313 HIV-infected patients using Kaplan-Meier analysis. Median time to detection of antiretroviral therapy (ART) failure using RVLM was 147 days; using US DHHS, it was 115 days; and using WHO guidelines, it was 1110 days. Median time for the development of first thymidine analog mutation was 594 days. The cost of RVLM was significantly lower than US DHHS. RVLM detected failure significantly sooner than CD4 count monitoring alone at a lower cost than US DHHS monitoring. RVLM is a potentially effective method of monitoring ART in resource-limited settings.

The Cost-Effectiveness of Cotrimoxazole in People With Advanced HIV Infection Initiating Antiretroviral Therapy in Sub-Saharan Africa

In sub-Saharan Africa, high mortality rates have been reported among patients with advanced HIV infection initiating antiretroviral therapy (ART). We evaluated the cost-effectiveness of expanding access to cotrimoxazole (CTX) for persons with HIV in averting mortality during the first 6 months of ART. We also evaluated possible cost savings related to prevention of specific opportunistic infections (OIs). We developed a decision-analytic model to estimate the incremental cost, deaths averted, and incremental cost-effectiveness ratio. The model compared 2 scenarios for providing CTX and evaluated potential benefits of increased CTX coverage in reducing deaths and cases of OI. The base case scenario represents an estimated current level of CTX coverage among adults initiating ART in low-income countries (65%). The comparator is 97% coverage (excluding only those with contraindications to CTX). We conducted sensitivity analyses on all parameters in the model. Full coverage reduced deaths from 94 to 72 per 1000 patients, averting 22 deaths during the first 6 months of ART compared with the base case. The incremental cost of moving from base case to full coverage was estimated at $3.29 per person on ART and $146.91 per death averted over 6 months. Additional benefits from averted OI cases would likely be realized as well as savings from averted OI treatment costs. Our findings suggest that expanding CTX coverage is a cost-effective approach to reducing mortality among patients who present with advanced HIV and initiate ART. The expansion of coverage may also yield benefits for OIs.

Life Expectancy of Persons Receiving Combination Antiretroviral Therapy in Low-Income Countries: A Cohort Analysis From Uganda

Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa. To estimate life expectancy of patients once they initiate cART in Uganda. Prospective cohort study. Public sector HIV and AIDS disease-management program in Uganda. 22 315 eligible patients initiated cART during the study period, of whom 1943 were considered to have died. All-cause mortality rates were calculated and abridged life tables were constructed and stratified by sex and baseline CD4 cell count status to estimate life expectancies for patients receiving cART. The average number of years remaining to be lived by patients who received cART at varying age categories was estimated. After adjustment for loss to follow-up, crude mortality rates (deaths per 1000 person-years) ranged from 26.9 (95% CI, 25.4 to 28.5) in women to 43.9 (CI, 40.7 to 47.0) in men. For patients with a baseline CD4 cell count less than 0.050 × 10(9) cells/L, the mortality rate was 67.3 (CI, 62.1 to 72.9) deaths per 1000 person-years, whereas among persons with a baseline CD4 cell count of 0.250 × 10(9) cells/L or more, the mortality rate was 19.1 (CI, 16.0 to 22.7) deaths per 1000 person-years. Life expectancy at age 20 years for the overall cohort was 26.7 (CI, 25.0 to 28.4) additional years and at age 35 years was 27.9 (CI, 26.7 to 29.1) additional years. Life expectancy increased substantially with increasing baseline CD4 cell count. Similar trends are observed for older age groups. A small (6.4%) proportion of patients were lost to follow-up, and it was imputed that 30% of these patients had died. Few patients with a CD4 cell count greater than 0.250 × 10(9) cells/L initiated cART. Ugandan patients receiving cART can expect an almost normal life expectancy, although there is considerable variability among subgroups of patients. Canadian Institutes of Health Research.

Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies

Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a limited repertoire of drugs. To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation. Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 [interquartile range (IQR) 144-338] at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories. These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.

Determination of the Incidence of Tuberculosis in Low‐Income Countries

To the Editor—We read with interest the report by The Antiretroviral Therapy in Low-Income Countries Collaboration of the International epidemiological Databases to Evaluate AIDS (IeDEA) andThe ART Cohort Collaboration on tuberculosis (TB) after initiation of antiretroviral therapy in low-income and high-income countries [1]. The authors do notmention the number of patients who were already receiving treatment for TB when the antiretroviral therapy was started (were the data not available?). However, they do mention that programs in lower-income countries routinely screened patients for TB before they commenced HAART. It is unclear to us whether patients being given treatment for TB at the start of HAART were included in the analysis. We propose that they should have been excluded from the study population if the aim of the study was to determine the incidence of TB and to compare the incidence rateratios for new TB infections. Indeed, in contrast to in high-income countries, in low-income countries, TB is one of the main reasons to initiate HAART. In Malawi, for example, from July through September 2005, 12% of the patients who started HAART did so because of TB [2]. During treatment for TB, by definition these patients cannot develop a new TB infection. We suppose that, if this approach were taken, the conclusions of the report would remain the same, but the calulations may change slightly. If the number of patients not receiving treatment for TB who started HAART is used as the denominator, the real incidence of TB in low-income countries will be even higher, particularly soon after the initiation of HAART.

Pediatric clinical pharmacology and its implications for antiretroviral drug development

Highly active antiretroviral therapy, which is widely available throughout developed countries, has become increasingly effective for treating the human immunodeficiency virus. In contrast, access to antiretroviral therapy in low-income countries is difficult at best. Thus, antiretroviral therapy for pediatric patients in resource-rich countries predominantly targets new drugs, and in low-income countries focuses on acquiring inexpensive, generic antiretroviral compounds available in pediatric-friendly formulations. Regardless of the economic region, success of antiretroviral therapy in pediatric patients depends upon our understanding of the physiological differences in drug absorption and disposition that occur with age, and our ability to adjust antiretroviral dosing according to these changes. The purpose of this review is to describe these differences and present recently published pharmacokinetic data of antiretrovirals in pediatric patients. Antiretroviral pharmacokinetic data in pediatric patients are limited. Recent data, however, continue to illustrate that antiretroviral pharmacology differs in children and adolescents when compared with adults. This review describes our current understanding of pharmacology in pediatric patients and summarizes key pharmacokinetic data on antiretroviral agents presented over the past year. We briefly describe how pediatric pharmacology impacts future research and drug development of antiretroviral agents.

Cost-effectiveness and cost-benefit in the prevention of mother-to-child transmission of HIV in developing countries

Approximately 25-30% of infants born to HIV-infected mothers in developing countries are infected with HIV. A range of approaches exists to reduce the rate of mother-to-child transmission (MCT). Currently however the only therapeutic approach proven to reduce such vertical transmission is the administration of zidovudine therapy during pregnancy delivery and the neonatal period in the absence of breast-feeding. The authors review economic evaluation as an approach to help guide the development of policies on preventing MCT in developing countries drawing from studies evaluating anti-retroviral therapy in sub-Saharan Africa and Thailand. Principles of economic evaluation are discussed followed by a review of available evidence and the consideration of the sensitivity of estimates to parameter variation the reliability of parameter estimates model completeness and comparability and affordability. Future evaluations of MCT interventions should include economic evaluation to determine whether the intervention if found to be effective can or should be implemented as a public health measure. Such economic evaluations should be clear and include a sensitivity analysis of the most important variables thought to influence effectiveness and costs. Affordability should also be considered and multiple outcome measures and frames of reference used.