Stock-outs! Improvisations and processes of infrastructuring in Uganda’s HIV/Aids and malaria programmes

ABSTRACT

This paper examines the stock-outs of medicines and diagnostic devices in Uganda. Our aim is to trace and compare interruptions in the supply of antiretrovirals and Rapid Diagnostic Tests in order to provide an ethnographic account of the complex role that improvisations play within global health infrastructures. We will argue that the fragmented and mobile infrastructures of these key global health technologies require and necessitate improvisations by the different actors involved as well as on almost all levels of the Ugandan health-care system. The extent and abundance of improvisations in itself works to acquire infrastructural capacities, a process that we will call the infrastructuring of care and treatment. We will also show how this process of infrastructuring of care and treatment – here rendered visible through improvisations – produces new dilemmas and uncertainties. Our approach to infrastructure challenges technocratic overtones prevalent in current debates around the much-needed strengthening of health systems. Our study of stock-outs aims to show how the infrastructure of under-resourced health systems is maintained by a complex nexus of socio-material practices and improvisations.     

Hatching success and survival of fish early life stages in a chronic exposure to nevirapine: a case study of the Mozambique tilapia

The anti-retroviral nevirapine has been detected in surface waters throughout South Africa and its effects on non-target aquatic animals are still unknown. The aim was to investigate the potential effects of nevirapine on the hatching success and survival of Oreochromis mossambicus early life stages through a chronic exposure. The exposer started with newly fertilized O. mossambicus eggs and concluded 30 days after hatching. Environmental relevant concentration of nevirapine (1.48 µg/l) was used in a static renewal system and a controlled environment (27 ± 1°C; 14:10 day/night cycle). The main endpoints assessed included hatching success and survival; a morphological assessment was also done on whole individual on day 1 and 30 post-hatching to identify any physical abnormality. Nevirapine had no noticeable effects on the hatching success and survival of O. mossambicus larvae; no statistically significant differences were observed between the control and the nevirapine exposed fish (p > 0.05).     

The use of a triple nucleoside-nucleotide regimen for nonoccupational HIV post-exposure prophylaxis

OBJECTIVES: Nonoccupational post-exposure prophylaxis (NPEP) for HIV is recommended after high-risk sexual exposure. Because of the high incidence of intolerable side effects observed with protease inhibitor- and zidovudine-based NPEP regimens, our unit changed standard NPEP treatment to 28 days of tenofovir-lamivudine-stavudine (TDF-3TC-d4T). The aim of this study was to compare side effects and numbers of individuals completing NPEP before and after this change. METHODS: Parameters were compared amongst individuals commencing the following NPEP regimens: zidovudine-lamivudine (ZDV-3TC), zidovudine-lamivudine-nelfinavir (ZDV-3TC-NFV) and TDF-3TC-d4T. RESULTS: A total of 385 individuals received ZDV-3TC (n = 36), ZDV-3TC-NFV (n = 225) or TDF-3TC-d4T (n = 137) as NPEP for the first time between June 1999 and November 2003. Noncompletion rates were 25%, 32% and 15%, respectively (P = 0.001), with odds ratios for noncompletion being 2.0 [95% confidence interval (CI) 0.8-4.8] and 2.7 (95% CI 1.6-4.8) in the first two groups compared with the TDF-3TC-d4T group (P = 0.008). Adverse events were less common in the TDF-3TC-d4T group, with significantly lower rates of nausea and headache, but significantly higher rates of peripheral neuropathy and asymptomatic raised transaminases. There was no HIV seroconversion in any group. CONCLUSIONS: TDF-3TC-d4T is significantly better tolerated than ZDV-3TC or ZDV-3TC-NFV as NPEP and results in greater numbers of individuals completing 28 days of treatment.     

In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs

Introduction:

The in vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process.

Objective:

To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans.

Methods:

Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated.

Results:

The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model.

Conclusions:

The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance.     

Pricing of drugs and donations: options for sustainable equity pricing

Effective medicines exist to treat or alleviate many diseases which predominate in the developing world and cause high mortality and morbidity rates. Price should not be an obstacle preventing access to these medicines. Increasingly, drug donations have been established by drug companies, but these are often limited in time, place or use. Measures exist which are more sustainable and will have a greater positive impact on people's health. Principally, these are encouraging generic competition; adopting into national legislation and implementing TRIPS safeguards to gain access to cheaper sources of drugs; differential pricing; creating high volume or high demand through global and regional procurement; and supporting the production of quality generic drugs by developing countries through voluntary licenses if needed, and facilitating technology transfer.