Abstract
Introduction: In the highly active anti-retroviral therapy (HAART) era, acquired immunodeficiency syndrome (AIDS)-related causes of death have declined, while non-AIDS-related causes, especially drug overdose and liver disease, have become a leading cause of death in persons with human immunodeficiency virus (HIV). Excess mortality among HIV-infected patients has been identified in those with substance use dependence. Our aim was to review the recent literature regarding the impact of HIV/AIDS on the current drug overdose epidemic with respect to the HAART era (1997 onwards). Methods: This systematic review screened Pubmed database using search terms (HIV, AIDS, HAART, overdose, hepatitis, nephropathy, opioid, acetaminophen, methadone) and included cohort studies with derived mortality rates while excluding individual case reports, commentaries, letters, and publications over 20 years old. The crude overdose mortality rate (COMR) for each study was used to calculate a pooled COMR for each region during the post-HAART era. Calculation of 95% confidence intervals (CI) for COMR used 5% alpha. Results: The COMR in HIV-infected persons was calculated for 17 cohort studies that analyzed cause of death in 22,414 total cases of HIV infected individuals who died from overdose in the United States, Canada, Puerto Rico, Europe, and Asia. The COMR worldwide during the pre-HAART era was 4.0% (CI 0.9-7.16) but this figure significantly increased to 17.5% (CI 12.4-22.7) during the post-HAART era. Factors that contributed to the rising COMR included: demographic factors, chronic pain, acetaminophen use, intravenous drug use, prescription drug addiction, HAART use, and end-organ disease (nephropathy, liver disease, neuro-cognitive disorder). Conclusion: In the HAART era, AIDS-related causes of death declined, while deaths due to overdose significantly increased in HIV patients. The rise in COMR was primarily attributable to pharmaceutical drugs for pain management. AIDS-related end-organ diseases may possibly impair metabolism and physiologic responses to drug overdose. Future research should focus on expanded COMR reporting, drug misuse, and prognostic markers.
Highlights
In the highly active anti-retroviral therapy (HAART) era, acquired immunodeficiency syndrome (AIDS)-related causes of death have declined, while non-AIDS-related causes, especially drug overdose and liver disease, have become a leading cause of death in persons with human immunodeficiency virus (HIV)
We found the Crude Overdose Mortality Rate (COMR) during the HAART era was 5.30% while the COMR during the post-HAART era increased to 19.50% (95% Confidence Interval (CI) 10.51-28.39) in Asia
We found the COMR in the pre-HAART era was 7.26% (5.53-8.99) while the COMR due to overdose during the post-HAART era increased to 13.63% (10.56-16.70) in Europe
Summary
In the highly active anti-retroviral therapy (HAART) era, acquired immunodeficiency syndrome (AIDS)-related causes of death have declined, while non-AIDS-related causes, especially drug overdose and liver disease, have become a leading cause of death in persons with human immunodeficiency virus (HIV). Excess mortality among HIV-infected patients has been identified in those with substance use dependence. Considerable progress has been made in reducing the impact of the HIV epidemic, there remains excess mortality among HIV infected patients diagnosed with substance use dependence [7, 8]. There is a demand for research expanding HAART therapy coverage to reduce HIV transmission among high-risk, vulnerable populations. The “seek, test, treat, and retain” model is based on the idea that by increasing HIV testing and effective enrollment into treatment plans with Highly Active Antiretroviral Therapy (HAART), the viral load among HIV positive individuals would be reduced resulting in decreased transmission of HIV at a population level [9]. Clinical research is needed to aggressively seek out high-risk, hard-to-reach substance abusers and to offer them HIV testing, access to treatment, and the necessary support to remain in treatment-both for HIV and for substance abuse [10]
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