Antiretroviral Provision Research Articles

Lack of Appropriate Treatment for People with Comorbid HIV/AIDS and Epilepsy in Sub‐Saharan Africa

To the Editors: We would like to draw your readership's attention to an emerging problem in epilepsy care in resource poor settings, particularly for regions heavily impacted by the HIV/AIDS pandemic such as sub-Saharan Africa (SSA). Through the efforts of the Global Fund, the President's Emergency Plan for HIV/AIDS Relief (PEPFAR), and the World Health Organization's three by five initiative, people in southern Africa are now gaining access to antiretroviral (ART) agents. Access to ARTs for people in the SSA region has been long-awaited and is clearly a humanitarian necessity—not only to decrease the global morbidity and mortality of HIV/AIDS, but also to facilitate social, economic, and political stability and development in such regions. Triomune, which contains stavudine, lamivudine, and nevirapine (NVP), is the most common fixed-dose, combination provided. In reality, many public ART clinics in SSA have only Triomune routinely available. Second-line agents are not affordable or accessible, particularly in the rural areas. Unfortunately, for people in resource-limited setting with epilepsy who also require ART therapy, access to ARTs represents a mixed blessing. Phenobarbitone is the mainstay of treatment for people with epilepsy in SSA. NVP's half-life is substantially shortened by the use of such enzyme-inducing agents. Coadministration of Triomune with the older, enzyme-inducing anticonvulsants results in suboptimal levels of NVP (L'Homme et al., 2006), which will likely lead to NVP resistance and ART treatment failure (Nowak et al., 1997). Development of HIV resistance to NVP has a negative impact on the health of the person undergoing treatment as well as public health implications for the long-term efficacy of presently affordable ART regimens. Newer antiepileptic drugs (AEDs) without enzyme induction properties are at present virtually unavailable in the region. This evolving situation places people with comorbid epilepsy and HIV in resource-poor regions in an untenable situation—essentially for each of these conditions they have one treatment available, but combining the two treatment (Triomune + phenobarbitone) has serious potential adverse outcomes for the individual as well as major public health implications for the community at large. Whether epilepsy care providers and/or ART clinic staff are aware of this concerning situation is unclear. ART provision has been largely facilitated by the development of separate, stand-alone clinics, and exchange between HIV/AIDS and epilepsy healthcare providers in Africa may be quite limited despite the reality that both conditions are exceedingly common in SSA relative to other parts of the world. We believe this is a complex, urgent, and important issue that requires the consideration and attention of international groups such as the International League against Epilepsy, the World Health Organization, and UNAIDS. Recognized interactions between NVP and TB treatment regimens have resulted in the development of recommendations for and access to alternative ART regimens for individuals with HIV/AIDS and TB comorbidity (Moreno et al., 2006). Similar attention and consideration is needed for persons suffering from HIV/AIDS and epilepsy.

Provision of HIV treatment in HIV preventive vaccine trials: a developing country perspective

HIV treatment for participants who become infected during HIV vaccine trials has been the focus of ethical controversy. The obligations of sponsors to ensure that participants have access to antiretrovirals have been a particular focus of this debate.This paper presents three arguments that have been made in this regard, and some of their limitations, in anticipation of HIV vaccine trials in South Africa.The first argument is that HIV risk behaviour increases in such trials, and HIV infection can be viewed as a research-related injury, justifying sponsor provision of treatment on grounds of compensation for harm. We conclude that risk-behaviour studies to date do not show general increases in risk behaviour that could constitute the basis for a general obligation. Participation may well adversely impact on risk behaviour for some individuals, and conceivably this could be demonstrated. This argument may, therefore, have merit at the individual level; however, it seems a weak platform from which to argue that sponsors should treat all HIV infections acquired during trials.The second argument is that treatment should be provided based on distributive justice. We conclude that traditional concepts of “distributive justice” in research appear limited in justifying obligations of sponsors to ensure access to antiretrovirals. Further, using research initiatives to reduce global health care inequities is controversial, and even proponents may disagree about the fairest use of finite resources.The third argument is that sponsors should ensure antiretroviral access on grounds of beneficence; namely, the maxim that if one can do something beneficial without sacrificing anything of comparable significance, it ought to be done. Thus, sponsors should provide more interventions than those minimally required to conduct the research. However, beneficence may demand levels of altruism that exceeds what is reasonable.While the latter arguments may provide stronger justifications than the first, it is difficult to use these arguments to establish that sponsor provision of antiretrovirals to infected individuals is obligatory.

Creation of a drug fund for post-clinical trial access to antiretrovirals

The long running debate about clinical trial sponsors’ responsibility for providing treatment to patients after a trial has ended does not seem likely to end soon. In September 2003 the World Medical Association postponed its decision about whether or not the Declaration of Helsinki should be revised to reflect concerns that the US government and the pharmaceutical industry have expressed about post-trial treatment. Paragraph 30 of the Declaration of Helsinki currently states: “At the conclusion of the study every patient entered into the study should be assured of access to the best proven prophylactic diagnostic and therapeutic methods identified by the study”. The proposed revision to paragraph 30 would introduce two main changes: that the physician should make every effort to see that patients receive treatment once it has been approved by appropriate authorities and that the physician is required to explicitly tell patients if they are unlikely to continue receiving treatment from sponsors after they leave the study. The ethical concerns over the undertaking of clinical trials in developing countries especially with respect to the standard of treatment that should be provided to trial participants have resulted in little research in countries where interventions are needed most. The initiation of preventative HIV vaccine trials has been delayed by debate about the provision of antiretrovirals to participants. (excerpt)

Concerns over antiretroviral provision voiced in South Africa

Concerns over antiretroviral provision voiced in South Africa