HIV This Week

Tossonian HK, Raffa JD, Grebely J, Trotter B, Viljoen M, Mead A, Khara M, McLean M, Duncan F, Fraser C, Devlaming S, Conway B. Methadone Dosing Strategies in HIV-Infected Injection Drug Users Enrolled in a Directly Observed Therapy Program. J Acquir Immune Defic Syndr 2007 July 1; 45(3):324-7.

Tossonian and colleagues have measured methadone dose adjustments and treatment responses after nevirapine (NVP)-, efavirenz (EFV)-, ritonavir-boosted lopinavir (LPV/r), or atazanavir (ATV; with or without ritonavir)-based highly active antiretroviral therapy (HAART) was initiated in injection drug users (IDUs). The authors identified 120 IDUs receiving HAART and methadone within a directly observed therapy (DOT) program. Follow-up was according to clinical standards, with changes in methadone dose being made as required to achieve clinical stabilization within the first 3 months of HAART. Their results showed that the observed median methadone dose changes from baseline were 20 mg/d (P < 0.001) in patients on NVP, with 32 (86%) of 37 patients requiring daily dose increases, and 7.5 mg/d (P = 0.004) in patients on EFV, with 11 (61%) of 18 patients requiring daily dose increases. Conversely, median changes were 0 mg/d for patients on LPV/r (P = 0.56) or ATV (P = 0.95). Virologic suppression (HIV RNA <400 copies/mL) was achieved in 26 (70%) of 37, 12 (67%) of 18, 25 (76%) of 33, and 24 (75%) of 32 patients receiving NVP-, EFV-, LPV/r-, and ATV-based regimens, respectively (P = 0.89). The authors concluded that although methadone-based DOT can be a successful tool for the co-administration of HAART, careful monitoring is required to ensure that methadone withdrawal does not adversely affect the goals of treatment, particularly when non-nucleoside reverse transcriptase inhibitors are used.

Editors’ note: Monitoring the need for an increase in methadone dosage is clearly required for patients being started on nevirapine or efavirenz. The majority of drug substitution patients placed on these antiretroviral medications will require an adjustment of methadone dose to achieve good drug substitution cover and improve the likelihood of antiretroviral drug adherence and viral suppression.

Tirwomwe JF, Rwenyonyi CM, Muwazi LM, Besigye B, Mboli F. Oral manifestations of HIV/AIDS in clients attending TASO clinics in Uganda. Clin Oral Investig 2007 Sep;11(3):289-92.

The objective of the study is to establish the prevalence of oral manifestations and their influence on oral functions. A total of 514 subjects aged 18 to 58 years (mean 42 years) were randomly recruited from five The AIDS Support Organization (TASO) clinics in Uganda. They were clinically examined for oral lesions under field conditions by four trained dentists based on World Health Organization criteria. Women constituted 74.5% of the study population. Oral manifestations were recorded in 72% of the subjects, out of which 70% had candidiasis of pseudomembranous, erythematous, and angular cheilitis variants. Non-Hodgkin’s lymphoma, atypical ulcers, necrotizing periodontitis, and hairy leucoplakia were least frequently observed in the subjects. Of those who had oral lesions (n = 370), 68.4% had some form of discomfort in the mouth. Tooth brushing, chewing, and swallowing were frequently associated with discomfort. Reported forms of discomfort were dry mouth, increased salivation, and burning sensation especially on taking salty and spicy foods or acidic drinks. Only 8.5% (n = 44) of the subjects were taking medications specifically for oral lesions, which included antifungal, antiviral, and antibacterial agents. None of the subjects were on antiretroviral therapy. Oral lesions associated with human immunodeficiency virus/acquired immunodeficiency syndrome in TASO clients is a major public health problem requiring education in recognition and appropriate management.  

Editors’ note: Oral candidiasis, also known as thrush, is common among people living with HIV in Uganda attending TASO clinics. Identifying the problem and treating it is important as eventually the pain and discomfort do affect eating and eventually nutritional status.

Mullan F, Frehywot S. Non-physician clinicians in 47 sub-Saharan African countries. Lancet 2007; [Epub ahead of print].

Many countries have health-care providers who are not trained as physicians but who take on many of the diagnostic and clinical functions of medical doctors. The authors identified non-physician clinicians in 25 of 47 countries in sub-Saharan Africa, although their roles varied widely between countries. In nine countries, numbers of non-physician clinicians equalled or exceeded numbers of physicians. In general non-physician clinicians were trained with less cost than were physicians, and for only 3-4 years after secondary school. All non-physician clinicians did basic diagnosis and medical treatment, but some were trained in specialty activities such as caesarean section, ophthalmology, and anaesthesia. Many non-physician clinicians were recruited from rural and poor areas, and worked in these same regions. Low training costs, reduced training duration, and success in rural placements suggest that non-physician clinicians could have substantial roles in the scale-up of health workforces in sub-Saharan African countries, including for the planned expansion of HIV prevention and AIDS treatment programmes.

Editors’ note: “Clinical Officers” rather than physicians are providing care on the frontlines directly to patients in many countries throughout sub-Saharan Africa, meaning that task shifting has already been underway for many years. As work proceeds to examine provider roles, patients’ needs, and rational deployment of human resources for health, the potential of clinical officers is receiving increasing attention.

Funding for scaling-up antiretroviral treatment (ART) in low-income countries has increased substantially, but the lack of human resources for health (HRH) is increasingly being identified as an important constraint for scaling-up ART. In a clinic run by Médecins Sans Frontières in Siem Reap, Cambodia, Van Damme and colleagues documented the use of doctor-time for ART in September 2004 and in August 2005, for different phases in ART (pre-ART, ART initiation, ART follow-up Year 1, & ART follow-up Year 2). Based on these observations and using a variety of assumptions for survival of patients on ART (between 90 and 95% annually) and for further reductions in doctor-time per patient (between 0 and 10% annually), the authors estimated the need for doctors for the period 2004 till 2013 in the Siem Reap clinic, and in a hypothetical district in sub-Saharan Africa. In the Siem Reap clinic, the authors found that from 2004 to 2005 the doctor-time needed per patient was reduced by between 14% and 33%, thanks to a reduction in number of visits per patient and shorter consultation times. In 2004, 2.06 full-time equivalent (FTE) doctors were needed for 522 patients on ART, and in 2005 this was slightly reduced to 1.97 FTE doctors for 911 patients on ART. By 2013, Siem Reap clinic will need between 2 and 5 FTE doctors for ART. In a district in sub-Saharan Africa with 200,000 inhabitants and 20% adult HIV prevalence, using a similar doctor-based ART delivery model, between 4 and 11 FTE doctors would be needed to cover 50% of ART needs. The authors conclude that ART is labour intensive. Important reductions in doctor-time per patient can be realized during scaling-up. The doctor-based ART delivery model analysed seems adequate for Cambodia. However, for many districts in sub-Saharan Africa a doctor-based ART delivery model may be incompatible with their HRH constraints.

Editors’ note: Physician time considerations in resource constrained settings should prompt consideration of alternate delivery models for scale-up, involving clinical officers, nurse practitioners, nurses and community adherence and support counsellors, among others. Determining the best utilisation of available human resources is a key to achieving favourable outcomes for patients and their families.

Macqueen KM, Namey E, Chilongozi DA, Mtweve SP, Mlingo M, Morar N, Reid C, Ristow A, Sahay S, Hptn T, Team SO. Community perspectives on care options for HIV prevention trial participants. AIDS Care 2007;19:554-60.

There is on-going global debate and policy-setting concerning researchers’ obligations to meet the health needs of people participating in HIV prevention trials in resource-poor settings. The perspectives of local community stakeholders on this issue are poorly understood as most of what is presented on behalf of communities where research takes place is anecdotal commentary. Using qualitative methods (130 in-depth interviews and 20 focus groups) MacQueen and colleagues assessed perceived fairness of different strategies to meet the health needs of women who become HIV-infected during a hypothetical vaginal microbicide trial. Respondents included HIV prevention research participants, community stakeholders and health-care service providers in ten sites in seven countries (South Africa, Malawi, Tanzania, Zimbabwe, Zambia, India, US). Many respondents perceived referrals to be a potentially fair way to address care and treatment needs but concerns were also voiced about the adequacy of local health-care options and the ability of trial participants to access options. Most respondents viewed the provision of antiretroviral treatment by researchers to HIV-infected trial participants as unfair if treatment was not sustained beyond the end of the trial. The results underscore the importance of effectively linking trial participants to sustainable, community-based treatment and care.

Editors’ note: This formative research with women in ten communities in Africa, India and the USA informed policy, not only at Family Health International, but among other research and community partners around the world. More information on the issues of standard of prevention and access to care is available from UNAIDS through two publications: Ethical considerations for biomedical HIV prevention trials and Good Participatory Practices in biomedical HIV prevention trials.

Ethical principles of beneficence and justice combined with international human rights norms and standards create certain obligations on researchers, sponsors and public health authorities. These include treatment provision for participants enrolled in clinical trials of vaccines, drugs and other new preventive and curative technologies and methods. However, these obligations are poorly defined in practical terms, inconsistently understood or inadequately applied. Vaccine clinical trial designs normally define standards of prevention applicable to the population where the trial is to take place. The present document addresses specifically the setting of standards applicable to care and treatment in vaccine trials. The lack of clear guidance on how to achieve the optimal synergy between the development of new health technologies, on the one hand, and the promotion and protection of ethical and human rights principles, on the other, is a barrier to the progress of health research and therefore to the advancement of public health. The World Health Organization and UNAIDS have engaged in a series of consultations in Africa, the Americas, Asia and Europe to reflect on how this aim could best be achieved. This document highlights the outcome of these consultations. It proposes a structured approach to consensual decision making in the context of the clinical trial of vaccines against such public health challenges as HIV and newly emerging or threatening epidemics. A structured approach involving investigators and sponsors in a consultative process with trial communities and other stakeholders in research will ensure that the needs and legitimate expectations of trial participants are appropriately met, obligations towards them are delivered and, as a result, ethical research is facilitated in the interest of public health.

Editors’ note: Who will provide and who will pay for the treatment and care of people who become infected during a biomedical HIV prevention trial has been hotly debated now for ten years. UNAIDS in collaboration with WHO has revised Ethical considerations for biomedical HIV prevention trials and in collaboration with the AIDS Vaccine Advocacy Coalition, and a Working Group with diverse membership, has created Good Participatory Practices in biomedical HIV prevention trials. Both of these documents make it clear that providing access to antiretroviral treatment for those who seroconvert in an HIV prevention trial is the accepted standard.