Directly observed therapy (DOT): from tuberculosis to HIV

BACKGROUND: Combination antiretroviral therapy, which is the standard of care since 1996, has been demonstrated to be very effective in suppressing plasma viral load in patients infected with HIV. Optimal benefit from antiretroviral drugs, however, is obtained when the patient adheres strictly to the rigorous treatment regimen. For some patients it is difficult to obtain good adherence to antiretroviral regimens. In response to these concerns, different strategies, such as directly observed therapy, have been proposed to attempt to improve adherence to antiretroviral treatment. Directly observed therapy is a strategy that has its roots in the treatment of tuberculosis and it consists essentially of taking the medication in the presence of a health care provider or another designated person. This strategy has been recently tried in the treatment of HIV but its efficacy remains unknown. METHOD: A Medline and Medscape search was performed to review all pertinent publications on the use of directly observed therapy in HIV infection. RESULTS: Twenty-five papers published between 1996 and 2004 were selected. Almost all the studies were performed in industrialized countries in North America and Europe. The majority of the studies are retrospective, six of them comparing at least two strategies (directly observed therapy vs standard of care). Only one randomized trial has been found. The patients involved in the studies are intravenous drug users or particularly non-adherent patients. Almost all studies show a better rate of adherence or a better control of the viremia in patients on directly observed therapy. CONCLUSIONS: The directly observed therapy seems to be a valuable and feasible way to raise the adherence rate in HIV patients with a problem of non-adherence to antiretroviral treatments. Clinical trials are needed to evaluate the efficacy of this strategy to raise the adherence rate among patients who need additional support to take their antiretrovirals.     

U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States.

These recommendations update the February 4,2002, guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission. This report provides healthcare providers with information for discussion with HIV-1-infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented, and the factors influencing treatment considerations are highlighted in this report. The Perinatal HIV Guidelines Working Group recognizes that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving and will continually review new data and provide regular updates to the guidelines. The most recent information is available from the HIV/AIDS Treatment Information Service (available at http.//www.hivatis.org). In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of persons with HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1-infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy pregnancy is not a reason to defer standard therapy. Use of antiretroviral drugs in pregnancy requires unique considerations, including the possible need to alter dosage as a result of physiologic changes associated with pregnancy the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness of the drugs in reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily for HIV-1 infection, for reduction of perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy to infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen.     

Malaria and HIV co-infection in pregnancy in sub-Saharan Africa: impact of treatment using antimalarial and antiretroviral agents

Malaria and HIV infection represent severe public health problems in sub-Saharan Africa, and pregnant women are at increased risk because the two diseases intersect in pregnancy, causing adverse perinatal outcome. As access to antiretroviral drugs is increasing in the sub-region, and new combinations of antimalarial drugs are being implemented while more are being evaluated, there is potential for interactions between these therapies. In this report, the impact of treatment using antimalarial and antiretroviral agents in pregnant women with malaria and HIV co-infection was reviewed, using scientific publications identified through a Medline Entrez-Pubmed search with reference to sub-Saharan Africa. The safety and operational feasibility of use of antimalarial and antiretroviral agents to treat co-infected pregnant women were evaluated. Although use of these therapies was shown to improve the health of pregnant women with co-infection, low adherence, poor-quality drugs, resource scarcity, lack of infrastructure and inadequate treatment in sub-Saharan Africa continue to hamper treatment outcome. The absence of studies on interaction between antimalarials and antiretrovirals, as well as mounting evidence of treatment failure due to drug resistance and adverse drug reactions, in most parts of sub-Saharan Africa, make the establishment of new guidelines for the prevention of malaria and HIV infection during pregnancy imperative.     

HIV as a chronic disease considerations for service planning in resource-poor settings

This paper reviews the healthcare issues facing nations which have a substantial caseload of chronic HIV cases. It considers the challenges of extending antiretroviral coverage to an expanding caseload as supplier price rises and international trade agreements come into force to reduce the availability of affordable antiretrovirals just as the economic downturn restricts donor funding. It goes on to review the importance in this context of supporting adherence to drug regimens in order to preserve access to affordable antiretrovirals for those already on treatment, and of removing key barriers such as patient fees and supply interruptions. The demands of those with chronic HIV for health services other than antiretroviral therapy are considered in the light of the fearful or discriminatory attitudes of non-specialist healthcare staff due to HIV-related stigma, which is linked with the weakness of infection control measures in many health facilities. The implications for prevention strategies including those involving criminalisation of HIV transmission or exposure are briefly summarised for the current context, in which the caseload of those whose chronic HIV infection must be controlled with antiretrovirals will continue to rise for the foreseeable future.     

AIDS treatment in Africa: the risk of antiretroviral resistance

--In recent years, implementation of antiretroviral therapy in developing countries with a high prevalence of HIV-1 has been recognised as a public health priority. Consequently, the availability ofantiretroviral combination therapy for people with HIV is increasing rapidly in sub-Saharan Africa. --HIV treatment programmes are implemented according to the standardised, simplified public health guidelines developed by the World Health Organization (WHO). --However, the implementation of treatment programmes in Africa is hindered by several factors, including the lack of adequate immunological and virological laboratory monitoring, insufficient support for adherence to therapy, vulnerable health care systems and the use of suboptimal drug combinations. --These suboptimal treatment conditions increase the risk that resistant virus strains will emerge that are less susceptible to standard first-line combination therapy, thus threatening the long-term success of the treatment programmes. --The WHO has initiated HIVResNet, an international expert advisory board that has developed a global strategy for surveillance and prevention of antiretroviral drug resistance. --The Dutch initiative known as 'PharmAccess African studies to evaluate resistance' (PASER) is contributing to this strategy by creating a surveillance network in sub-Saharan Africa.     

World AIDS Conference

Several findings from the 1998 World AIDS Conference are presented regarding current HIV research. One finding is that early access to drugs for HIV infection is cost-effective, increases life span, and improves quality of life. Research is also being conducted at Massachusetts General Hospital to investigate whether a patient's immune system can ward off further infection if antiretroviral therapy is ceased. Other findings conclude that expanding Medicaid coverage may reduce the number of AIDS-related deaths, that there are fewer treatment options for those who are poor, and that women may need to begin HIV treatment earlier than men. Also, the Centers for Disease Control and Prevention (CDC) has found that the prevention of HIV infections is a cost-effective way to control the spread of the epidemic. Post-exposure practices and adherence are also discussed. The first case of an HIV strain that is resilient to 6 of the 11 approved drugs was presented.     

Illicit drugs, alcohol, and addiction in human immunodeficiency virus

Drug and alcohol use complicate both the prevention and treatment of human immunodeficiency virus (HIV) infection. Substance use is one of the major engines driving HIV transmission, directly, through the sharing of injection drug use equipment and indirectly, through increasing risky sexual behaviors. Drug and alcohol dependence compromise effective HIV treatment by influencing both access and adherence to antiretroviral therapy. Exposure to addictive substances may have direct immunosuppressive effects independent of their impact on access and adherence to treatment. Measures effective at minimizing HIV transmission attributable to drug and alcohol use include HIV testing and referral to treatment, syringe and needle exchange programs, opioid replacement therapy (i.e., methadone and buprenorphine), and behavioral interventions targeting HIV risk behaviors among both HIV-infected and HIV-uninfected people. Measures effective at optimizing HIV treatment among alcohol and drug-dependent patients include HIV testing with referral to treatment and substance use treatment that is linked to or integrated into HIV treatment. Due to the intertwining problems of substance use and HIV infection, physicians and other health care providers must address the issues of illicit drugs and alcohol use as mainstream medical problems in order to provide optimal care for HIV-infected patients.     

Clinical and Economic Implications of Non-Adherence to HAART in HIV Infection

Highly active antiretroviral therapy (HAART) has dramatically altered the natural history of HIV disease. Studies demonstrate that ≥95% adherence is necessary to garner the full benefits of HAART. However, appropriate adherence to treatment is difficult and challenging. This paper provides an overview of potential clinical and economic outcomes associated with poor adherence to HAART. Since there are no studies exploring the costs associated with poor adherence to HAART, we discuss potential direct and indirect costs accrued with more frequent treatment failures, selection of resistant strains, increased hospitalizations and a faster progression to AIDS associated with poor adherence to HAART. Additionally, we review studies of interventions and strategies to improve adherence to HAART. Although, single-focus interventions have enhanced the chances of achieving viral suppression by 10 to 23%, the literature has demonstrated that for long-term treatments, programs employing diverse interventions that continue over time are more effective. Under constrained healthcare budgets, government, healthcare managers and policy makers require accurate and timely information concerning the cost effectiveness of adherence intervention programs. We discuss considerations in determining the cost effectiveness of an adherence intervention program.     

Social meanings of adherence to antiretroviral therapy in Cambodia

Global expansion of antiretroviral therapy (ART) programmes for people living with HIV is the largest public health undertaking to date. Antiretroviral therapy adherence drives individual and programme outcomes, yet little is known regarding the determinants of these behaviours. We investigated beliefs and practices associated with ART use in Cambodia. In-depth interviews were conducted during 2005 with 27 people living with HIV who were recruited using a theoretical sampling strategy and analysed in Khmer and English using an inductive approach to code data and identify themes. Limited access to ART generated a sense of ART as rare and precious, with access granted by doctors once patients proved themselves dependable. The social construction of ART use was strict, precise and modern with ritualistic preparation and dosing procedures. Experiences of life-saving efficacy in self and others built a deep sense of trust. For many, ART was simply equated to life. Antiretroviral therapy dosing was prioritized and supported by an ever-present sense of remembering, reminder devices and social networks. Healthcare workers set norms and provided various forms of adherence support. Antiretroviral therapy use in Cambodia is shaped by the relationship between individuals and social and healthcare networks that set, encourage and enforce precise norms of ART use.     

Social meanings of adherence to antiretroviral therapy in Cambodia

Global expansion of antiretroviral therapy (ART) programmes for people living with HIV is the largest public health undertaking to date. Antiretroviral therapy adherence drives individual and programme outcomes, yet little is known regarding the determinants of these behaviours. We investigated beliefs and practices associated with ART use in Cambodia. In-depth interviews were conducted during 2005 with 27 people living with HIV who were recruited using a theoretical sampling strategy and analysed in Khmer and English using an inductive approach to code data and identify themes. Limited access to ART generated a sense of ART as rare and precious, with access granted by doctors once patients proved themselves dependable. The social construction of ART use was strict, precise and modern with ritualistic preparation and dosing procedures. Experiences of life-saving efficacy in self and others built a deep sense of trust. For many, ART was simply equated to life. Antiretroviral therapy dosing was prioritized and supported by an ever-present sense of remembering, reminder devices and social networks. Healthcare workers set norms and provided various forms of adherence support. Antiretroviral therapy use in Cambodia is shaped by the relationship between individuals and social and healthcare networks that set, encourage and enforce precise norms of ART use.     

Therapeutic vaccination for future management of HIV/AIDS

The investigation of novel and innovative treatment approaches for long-term management of HIV-infection has intensified due to the growing number of infected individuals worldwide and the constraints of resistance, toxicity and inconvenience associated with lifelong therapy. Current treatment relies entirely on antiretroviral drugs targeting various stages of the life cycle of HIV, rather than on leveraging the immune system. However, the boosting of HIV-specific immune responses in chronic infection offers a vast potential for synergy with antiretroviral drugs, thereby contributing to durable control of viral replication. A novel immunotherapeutic agent that delivers plasmid DNA to dendritic cells after topical skin application is the first therapeutic vaccine that has demonstrated immunological and clinical benefit in chronically infected rhesus macaques in combination with antiretroviral therapy.     

Optimal antiretroviral therapy for aging

The introduction of highly active antiretroviral therapy (HAART) has irrevocably changed the nature of the HIV epidemic in developed countries. Although the use of HAART does not completely restore health in HIV-infected individuals, it has dramatically reduced morbidity and mortality. Increases in life expectancy resulting from effective long-term treatment mean that the proportion of older people living with HIV has increased substantially in the past 15 years. Increasing age is associated with many complications including cardiovascular disease, neurological complications, kidney and liver dysfunction, and metabolic complications such as dyslipidaemia and diabetes. HIV infection and antiretroviral drugs have also been associated with similar complications to those seen with increasing age. The increase in HIV prevalence in older age groups has not been accompanied by the development of treatment guidelines or recommendations for appropriate antiretroviral therapy or clinical management in these patients.     

Treatment adherence to an antiretroviral regime: the lived experience of Native Hawaiians and kokua

Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity of people living with HIV, but treatment efficacy relies on strict adherence that is difficult for many consumers to manage. Results presented in this article are based on semi-structured in-depth interviews with Native Hawaiian consumers (n = 6) who reported moderate to low levels of overall HAART adherence, and based on their kokua, or primary support. All interviews were recorded on audiotape, transcribed verbatim, and analyzed using Grounded Theory methods. Research questions that guided the inquiry, included: What are the challenges of Hawaiians who report moderate to low levels of HAART adherence? How does non-adherence occur? What is the role of the kokua (primary caregiver) and/or family members in treatment adherence? What types of support enhance adherence? The unpredictability of living with HIV was a major challenge to adherence. Symptom distress and active use of alcohol and other drugs interfered with the capacity to appropriately adhere. Two patterns of non-adherence were identified: interrupted regime and intermittent use. Tangible and emotional types of support, sometimes delivered in culture-specific ways, were viewed as helpful in maintaining compliance and in resuming the regime when difficulties arose. The findings complement extant research on HAART by providing an understanding of adherence as a lived experience among Native Hawaiians and their kokua.     

Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death

Injection drug users (IDUs) continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART) in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes) provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.     

Tuberculosis and HIV infection in Brazil: magnitude of the problem and strategies for control

The aim of the article was to propose, based on an analysis of the current scenario and of the interaction between tuberculosis and AIDS, strategies to minimize the epidemiological impact of one disease over the other in Brazil. The manner by which health policies aimed at controlling the HIV/AIDS epidemic is analyzed -- such as access to antiretroviral drugs and campaigns for the early detection of HIV infection and for encouraging adherence to treatment - and their impact on the achievement of goals related to controlling tuberculosis. The implementation of measures for preventing the onset of tuberculosis in HIV-infected individuals, early detection of tuberculosis disease, and ensuring treatment adherence, is discussed. It is commented upon the role that Brazil may assume in the global effort to develop a therapeutic arsenal and the need for integrated work between the fields of tuberculosis and HIV/AIDS.