REVIEW OF CONTROL OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION IN NIGERIA.

The global scourge of human immunodeficiency virus (HIV) infection is inundating, especially in sub-Saharan Africa and in particular Nigeria which is home to 10% of the world's HIV-infected persons. The target of the millennium development goal 6 is to halt and reverse the spread of HIV/AIDS by 2015. HIV control in Nigeria was initially shrouded in denial and apathy. Subsequently, a more pragmatic approach was launched during the tenure of President Olusegun Obasanjo. Several policies were formulated. The national prevalence of HIV witnessed some progressive decline and is currently 4.1%. There is now improvement in both HIV awareness and counselling and testing. Greater access to antiretroviral therapy and other support services have also been witnessed with over 300,000 persons currently on drugs. Notable achievements have been recorded in prevention of mother to child transmission (PMTC). However, with increased access to antiretroviral therapy, antiretroviral drug resistance has become inevitable. Acquired drug resistance is high-82% and transmitted drug resistance ranges between 0.7 and 4.5%. The achievements were largely facilitated by international partnerships which have become more streamlined in recent years. A sustained shift to indigenously sourced financial and manpower resource has become imperative. It is also important to integrate HIV facilities with other existing health care facilities for sustainability and cost-effectiveness. In an attempt to strengthen the national response, President Goodluck Ebele Jonathan launched the President's Comprehensive Response Plan for HIV/AIDS in Nigeria. It is hoped that this well-articulated policy would be well implemented to significantly reverse the epidemic.

Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics.

The aim of this study was to examine the concordance between human in vivo and in vitro skin irritation classifications of cosmetic products and to evaluate the correlations between the different parameters. For that purpose, 22 formulations from product development test series, covering the full range of in vivo scores and representing different cosmetic product classes, were tested in vivo (modified Frosch-Kligman Soap Chamber Patch Test with repetitive occlusive application) and in vitro using two epidermis equivalents commercially available as kits (EpiDerm and EPISKIN) and one in-house model (Cosmital). In vivo, skin reactions (erythema, dryness and fissures) were visually evaluated and, in addition, skin redness and transepidermal water loss (TEWL) were measured by means of technical instruments. The parameters measured in vitro were the percent cell viability in the MTT reduction assay, with ET(50) determination, and the extracellular release of the pro-inflammatory mediator IL-1alpha and of the cytosolic enzyme lactate dehydrogenase (LDH), into the culture medium collected after topical application of the products for different exposure times (time-course assay). In general, good Spearman rank correlations could be observed between the different in vivo parameters (with the exception of TEWL and dryness at day 2). Furthermore, high correlation coefficients were obtained by comparing the different in vitro parameters (except for LDH release) and different models, which allowed to conclude that the results obtained with the different reconstructed epidermis models were very similar. A comparison between in vivo and in vitro parameters resulted in the best rank correlation for ET(50), then in decreasing order, for the percent MTT viability at 16 h, the IL-1alpha release and finally, for LDH release, where the correlation was generally low. A direct comparison of the mean total scores (sum of erythema, dryness and fissures at day 5) of the 22 products with the best predictor, ET(50) obtained with the three reconstructed epidermis models, using simple linear regression analysis resulted in a coefficient of correlation R=0.94 for EpiDerm, R=0.90 for Cosmital and R=0.84 for EPISKIN. Multivariate descriptive statistics showed that the in vitro parameters, MTT viability evaluated after the 16-h exposure and ET(50), as well as the in vivo parameters, sum of visual scores at day 5 and chromameter value, were the best endpoints to discriminate between irritant and non-irritant products. Using the in vivo mean total scores at day 5 with a cut-off value at 2 and the in vitro percent MTT viability after the 16-h exposure with a cut-off value at 50% to classify the products, the same two-by-two contingency table was obtained for all the three reconstructed epidermis models with sensitivity=92%, specificity=100% and observed concordance=95% (kappa=0.91; 95% confidence interval 0.74-1.08). This classification system was a satisfactory and relevant approach to discriminate the "irritant" from the "non-irritant" cosmetic products in this study. In conclusion, this study demonstrated the usefulness of reconstructed human epidermis equivalents for the in vitro assessment of the irritation potential of a series of cosmetic products. These models allow the measurement of quantifiable and objective endpoints relevant to in vivo irritative phenomena.

A summary report of the COLIPA international validation study on alternatives to the draize rabbit eye irritation test.

The principal goal of this study was to determine whether the results from a set of selected currently available alternative methods as used by cosmetics companies are valid for predicting the eye irritation potential of cosmetics formulations and ingredients and, as a consequence, could be valid replacements for the Draize eye irritation test. For the first time in a validation study, prediction models (PMs) that convert the in vitro data from an assay to a prediction of eye irritation were developed for each alternative method before the study began. The PM is an unequivocal description of the relationship between the in vitro and the in vivo data and allows an objective assessment of the reliability and relevance of the alternative methods. In this study, 10 alternative methods were evaluated using 55 test substances selected as representative of substances commonly used in the cosmetics industry (23 ingredients and 32 formulations). Twenty of the single ingredients were common to the European Commission/British Home Office (EC/HO) eye irritation validation study (Balls et al., 1995b). The test substances were coded and supplied to the participating laboratories. The results were collected centrally and analysed independently, using statistical methods that had been agreed before the testing phase began. Each alternative method was then evaluated for reliability and relevance in assessing eye irritation potential. Using the criteria of both reliability and relevance as defined in the study, the preliminary results indicate that none of the alternative methods evaluated could be confirmed as a valid replacement for the Draize eye irritation test across the full irritation scale. However, three alternative methods-the fluorescein leakage test, the red blood cell assay (classification model) and the tissue equivalent assay-each satisfied one criterion of reliability or relevance. Further investigation of the decoded data from this study to explore more fully the relationship between the in vitro data and the in vivo data is recommended. Such a review may allow the development of new prediction models to be tested in a subsequent validation study.

Evaluation of eye irritation potential: statistical analysis and tier testing strategies.

Eye irritation testing, specifically the Draize test, has been the centre of controversy for many reasons. Several alternatives, based on the principles of reduction, refinement and replacement, have been proposed and are being used by the industry and government authorities. However, no universally applicable, validated non-animal alternative(s) is currently available. This report presents a statistical analysis and two testing approaches: the partial least squares multivariate statistical analysis of de Silva and colleagues from France, the tier-testing approach for regulatory purposes described by Gerner and colleagues from Germany, and the three-step tier-testing approach of the US Interagency Regulatory Alternatives Group described by Gupta and Hill. These approaches were presented as three separate papers at the November 1993 Interagency Regulatory Alternatives Group (IRAG) Workshop on Eye Irritation Testing; they have been summarized and combined into the following three-part report. The first part (de Silva et al.) presents statistical techniques for establishing test batteries of in vitro alternatives to the eye irritation test. The second (Gerner et al.) and third (Gupta and Hill) parts are similar in that they stage assessment of information by using a combination of screening information and animal testing to effect reductions in animal use and distress.