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The efavirenz, a non nucleoside reverse transcriptase inhibitor of HIV-1, presents a marked pharmacokinetics variability related to an intense hepatic metabolism. Efavirenz is also a potent inducer. Central nervous system (CNS) toxicity associated with efavirenz therapy is a major cause of non adherence and therefore treatment failure. The literature has been analyzed to evaluate the level of evidence of the interest of a therapeutic drug monitoring for efavirenz. Several studies have reported that an efavirenz plasma concentration >1 000 ng/mL is a predictive factor of the viral response. Efavirenz plasma concentrations >4 000 ng/mL were associated to an increase frequency of CNS side effects. CNS toxicity was also more frequent in patients carrying the 516G > T mutation (CYP2B6*6 allele), associated with a significantly greater efavirenz plasma exposure. Non-randomized studies have reported the interest of efavirenz therapeutic drug monitoring to optimize viral response and prevent CNS toxicity, allowing to suggest a level of evidence "recommended" for efavirenz., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

Nevirapine, a HIV non nucleosidic reverse transcriptase inhibitor, displays an inter-individual variability in its pharmacokinetics parameters, related to its hepatic metabolism. Based on literature, is the nevirapine therapeutic drug monitoring relevant? In naïve and pre-treated HIV infected patients, the probability of achieving and maintaining an undetectable HIV viral load was significantly associated with a nevirapine plasma trough concentration (C(trough)) > 4 000 ng/mL. The probability of virologic failure was significantly associated with a C(trough) < 3 000 ng/mL. Concerning the exposure-toxicity relationship, the emergence of hepatotoxicity was more frequently associated with high C(trough), especially in case of HCV coinfection. Non-randomized studies have reported the interest of nevirapine therapeutic drug monitoring to optimize the virologic response and, to a lesser extent, to prevent hepatotoxicity. Therefore, the level of evidence of the interest of nevirapine therapeutic drug monitoring is "recommended"., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

The human immunodeficiency virus (HIV) protease inhibitor saquinavir displays a large inter-individual variability in its pharmacokinetic parameters, related to a low absorption rate and an important hepatic metabolism. Based on literature, is the saquinavir therapeutic drug monitoring relevant? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a saquinavir plasma trough concentration >100 ng/mL. Two studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of virologic response with a threshold value around 40 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 abdominal pains was more frequently associated with high concentrations of saquinavir, but without threshold value determination. Several studies, one of which was randomized, have reported the interest of saquinavir therapeutic drug monitoring to optimize the virologic response. Therefore, the level of evidence of the interest of saquinavir therapeutic drug monitoring is "recommended"., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

The HIV protease inhibitor lopinavir presents a wide inter-individual variability related to liver and intestinal metabolism involving CYP3A. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of lopinavir could improve patient care. In naïve or pretreated HIV-infected patients, no relationship could be evidenced between virological efficacy and trough lopinavir concentration, most likely because concentrations are above inhibitory concentrations. Although data are limited, patients with elevated triglycerides and cholesterol had trough lopinavir concentrations >8 000 ng/mL. These data suggest that the level of evidence of interest of lopinavir therapeutic drug monitoring is may be recommended in some situations such as children, pregnant women, pretreated patients if the number of mutations is <5, when coadministration with drug with metabolizing enzyme inducing properties is warranted and toxicity., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

The HIV protease inhibitor atazanavir presents a wide inter-individual variability related to an intense hepatic metabolism. Dose-dependent elevations of bilirubin have been frequently reported with atazanavir. Relative to literature, the atazanavir therapeutic drug monitoring can it be proposed? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a plasma trough concentration (C(min)) of atazanavir >200 ng/mL. Studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of the virologic response with a threshold value around 200 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 hyperbilirubinemia was more frequently associated with C(min) > 750-800 ng/mL. Non-randomized studies have reported the interest of atazanavir therapeutic drug monitoring to optimize the virologic response and prevent severe bilirubin elevations. Therefore, the level of evidence of the interest of atazanavir therapeutic drug monitoring is recommended., (© 2011 Société Française de Pharmacologie et de Thérapeutique.)

Despite a relative global stabilization of its incidence, HIV infection remains a major threat for public health, principally in Africa where it concerns more than 22 million people and constitutes the first cause of death on the continent. To face the emergency of the HIV/AIDS epidemics on the African continent, the primary goal is to make available to all patients free and efficient antiretroviral medications. Such a goal cannot be dissociated from large scale prevention campaigns. In 2000, Triomune, one of the first fixed dose combinations of three antiretrovirals (stavudine, lamivudine & nevirapine) was launched by the Indian drug company Cipla, specialized in the production of low cost medications. Its convenient pill burden (one pill twice a day) and its very low cost (around 30 US $ per month) make Triomune an appealing solution for the treatment of HIV/AIDS in Africa. Unfortunately, Triomune presents several drawbacks (low genetic barrier, frequent side effects) and one of its constituents is not used in Europe anymore. Other first line treatments are urgently needed.

Since the start of the new century, development aid targeted on health care has seen an unprecedented rise, driven by the fight against AIDS. This article shows how this struggle has been accompanied with a renewal of the economic paradigms governing international action in favour of health care in developing countries: the idea that an improvement in health care constitutes an unavoidable prerequisite to macroeconomic growth, rather than a consequence; the insistence on the founding of mechanisms for health insurance to finance the costs of health care, rather than covering the costs at the point of use by the health care users; a concern to impose price differentials for access to medicine in developing countries, and to introduce flexibility in the regulation of international intellectual property law; the priority to vertical programmes targeted on certain illnesses, thought to act as levers for a global reinforcement of health care systems. This article discusses the pertinence of these new paradigms in light of the evolution of the AIDS/HIV epidemic, and the international context.

The objective was to assess the cost-effectiveness ratio of HAART in the treatment of HIV infection. Two random samples were extracted from the database of the Rothschild Public Hospital, and patients were matched for age, sex and T4 cell counts: a first sample selected in 1996/97 of HAART treated patients (CAS group) and a second sample selected in 1994/95 of non-HAART treated patients (CONTROL group). Immune recovery and use of resources data were extracted and analyzed over two years for 196 included patients. Mean T4 cell count after two years was higher among CAS patients (344/mm3 vs. 234/mm3; p < 0.0001). CAS patients recorded a supplementary cost of antiretroviral treatments (+171%; p < 0.0001) balanced by savings in other drugs expenses (-62%; p = 0.0560) and in hospitalizations (-25%; NS). Overall, CAS patients presented a 15% (NS) lower medical cost than CONTROL patients.

Little is known about the costs of treating HIV-infected children in Africa. However, this is one of the factors that must be taken into account when assessing the cost-effectiveness of strategies aimed at reducing the transmission of HIV from mother to child. The aim of this study was to estimate the direct costs of the treatment of African children born to HIV-infected mothers and the additional costs of treating those children who are themselves infected with the virus. We assessed the direct costs of care for a sample of children born in 1996 to HIV-positive mothers participating in a clinical trial to evaluate the efficacy of administering a short course of zidovudine to the mother in the peri-partum period, in Abidjan, Ivory Coast (DITRAME ANRS 049a). We systematically reviewed the medical records of these children and recorded drug prescriptions, clinical investigations, consultations with medical specialists, hospital admissions and transportation costs during their first year of life. This study included 78 children, 15 of whom were HIV-positive. The mean cost of treatment was 1,671 FF (254 Euros) per child-year for infected children, 709 FF (108 Euros) more than the mean cost of treatment for HIV-negative children born to HIV-positive mothers. Thus, HIV infection resulted in a 74% increase in treatment costs. The mean cost of a drug prescription was 50 FF (7.6 Euros), and could have been halved if only generic drugs had been prescribed. This study was limited to the direct costs of pediatric HIV infection and did not take into account the cost of health service provision in Ivory Coast or the indirect costs for the family. These results were obtained in the context of a prospective clinical trial within a system providing free and unlimited access to health care. In a city where the mean salary of a civil servant is 900 FF (137 Euros) per month, the expenditure necessary to pay for the basic care of one HIV-infected child is high. Health-care services in sub-Saharan Africa should make more use of generic drugs and pediatric HIV infection provides a clear example of the benefits to be obtained by such a rational strategy for the use of scarce health resources.

The production of ganciclovir doses by a hospital pharmacy having the necessary facilities to reconstitute anticancer drugs would be of the utmost relevance regarding both protection of the nursing staff and therapeutic safety. As this activity is also economically worthwhile a large number of our colleagues would like to implement it. The aim of this work has was to take advantage of a 40 weeks production of ganciclovir dose by the pharmacy at Rangueil hospital in Toulouse so as to answer some of the questions raised by such a project. The savings achieved by the team at Brabois hospital in Vandoeuvre les Nancy could therefore be validated. They are expressed in fraction of flask per dose produced (0,265). Applied to the number of doses that we delivered over a 40 week period, this coefficient enabled us to estimate from the only datum which is initially available to us, namely the number of flasks used, the extra work load and the savings that could be made: given steady activity, the number of doses the pharmacy will have to prepare is equal to the number of flasks multiplied by 1.418 and, provided one opts for a production process mostly in batches, the savings will be equivalent to 37.5% of the flasks.

Mother to child transmission (MCT) of Human Immunodeficiency Virus (HIV) is the main cause of the spread of the HIV epidemic in the pediatric population. It is estimated that to date, three million children worldwide have been infected by HIV. The epidemic burden in developing countries is dramatic. Ninety-five percent of the world's HIV-infected women are living in developing countries. In industrialized countries, antiretroviral treatment of pregnant women and newborns with azidothymidine (AZT, ACTG 076 regimen) and discouraging breast feeding by HIV-infected mothers are effectively reducing MCT of HIV. However, there are three major obstacles to the systematic application of these strategies in developing countries: (a) difficulties in implementing the complex AZT administration and its corollary the avoidance of breast feeding; (b) the complexity of the logistics of the ACTG 076 regimen; (c) cost. Indeed, in developing countries the socioeconomic situation of the populations are precarious and health structures and services are underdeveloped. In addition, the anxiety and the reluctance of general population in the face of the HIV problem and the high prevalence of maternal anemia reduce the acceptability and safety of AZT treatment for pregnant women in developing regions. Only interventions that are applicable, acceptable, safe, affordable, of low cost and integrated into health system will be able to reduce HIV MCT. We now know that MCT occurs mostly during the perinatal period and the maternal viral load in blood, in cervical secretions and in breast milk appears to be the main determinant of transmission. Maternal vitamin A deficiency may also favor MCT of HIV. It is however possible that this association is confounded by the relationship between advanced maternal HIV disease (a known risk factor for transmission) and vitamin A deficiency. In spite of these uncertainties concerning determinants of MCT of HIV, several interventions have been designed. The first involves treating the mother with antiretroviral drugs for the perinatal period. The second is vaginal disinfection by application of virucidal antiseptics during the perinatal period. The third is to give vitamin A supplements to pregnant women and children. Finally, passive immunotherapy with anti-HIV antibodies applied to pregnant women and/or new born, may be beneficial. The feasibility, safety and efficacy of these potential interventions have not yet been demonstrated in developing countries. In view of the dramatic spread of HIV infection in these countries, the evaluation of these interventions is of utmost priority. These trials are necessary because of the public health emergency but should be performed in strict respect of human rights and medical ethics.