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The purpose of this study was to identify risk factors associated with the severity of acute ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in sub-Saharan Africa.A retrospective study was carried out at the dermatology department in collaboration with the ophthalmology department for SJS/TEN patients between January 2000 and December 2016 in Lomé (Togo). The severity of acute ocular involvement was evaluated using the Power classification, and the drug eruption score was assessed using de Bastuji-Garin classification.A total of 107 cases of SJS/TEN (84 cases of SJS, 20 cases of TEN and 3 cases of overlap syndrome) were analyzed. There were 71 women and 36 men, with an average age of 32.3±12.5 years (range: 5 to 75 years). Sulfonamides (37.4%) were the most commonly used drugs followed by nevirapine (22.4%). HIV serology was positive in 46 (58.2%) of the 79 patients tested. A total of 54 (50.5%) patients had acute ocular involvement, which was mild in 29.9% of patients, moderate in 13.1% and severe in 7.5%. In multivariate analysis, exposure to sulfadoxine was the sole factor associated with moderate or severe acute ocular involvement in SJS/TEN (adjusted odds ratio=3.3; 95% CI=[1.1; 10.2]).Exposure to sulfadoxine was identified in our study as a risk factor associated with the severity of acute ocular involvement in SJS/TEN. Multicenter studies should be conducted in sub-Saharan Africa to confirm this associated risk factor.

Pregnant women are exposed to numerous drugs and for obvious ethical reasons studies in this sensitive population arelimited. Information about the maternal pharmacokinetic (PK) changes and transplacental transfer of drugs prior to theiradministration to pregnant women would be highly useful. Indeed is it known that physiological changes during pregnancycan affect drug disposition. Time-varying pregnancy-related physiological parameters changes were implemented in fullPBPK models. They successfully predicted the disposition of 3 renally excreted drugs tenofovir (TFV), emtricitabine (FTC)and lamivudine (3TC) and one metabolized drug, nevirapine (NVP) for non-pregnant and pregnant populations. We foundthat both renal secretion and filtration changed during pregnancy. Changes in renal clearance secretion were related tochanges in renal plasma flow. Transplacental parameters estimated from ex vivo human placenta perfusion experiments implemented in PBPK models allowed good prediction of foetal TFV, FTC and NVP PK. Predictions were compared to observed cord blood concentrations to validate these models. Moreover, we have explored nevirapine foetal metabolism and concluded that even if the foetal metabolism is the same than the newborn one or a little more important, it is notlikely to impact foetal PK.; Les femmes enceintes sont exposées à de nombreux médicaments et les essais cliniques sont difficilement réalisables dans cette population, c'est pourquoi avoir une méthode qui permet d'estimer l'ampleur des modifications de pharmacocinétique chez la femme enceinte et le passage transplacentaire est essentiel. En effet les modifications physiologiques prennent place durant cette période clé. Nous avons développé des modèles pharmacocinétiques basé sur la physiologie (PBPK) et intégré les modifications physiologiques connues survenant durant la grossesse. Ils décrivent bien la pharmacocinétique de 3 antirétroviraux éliminés par le rein, le ténofovir (TFV), l'emtricitabine (FTC) et la lamivudine (3TC) et d'une molécule métabolisée par le CYP3A4, 2D6 et 2B6, la névirapine (NVP) et ceci pour différentes voies d'administration et pour des populations enceintes et non enceintes. De plus les clairances individuelles disponibles pour le TFV, le FTC et le 3TC tout au long de la grossesse ont permis d'explorer l'évolution de la sécrétion rénale. Celle-ci évoluerait proportionnellement au débit plasmatique rénal. L'intégration dans les modèles PBPK, des paramètres estimés à partir de l'expérience ex-vivo de cotylédon humain perfusé, a permis la prédiction de la cinétique foetale en fin de grossesse du TFV, FTC et NVP. Les prédictions ont été validées en les comparants aux concentrations mesurées au sang de cordon à l'accouchement. De plus, pour la névirapine nous avons exploré le métabolisme foetal et en avons conclu que même si celui-ci existe et est proche voir un peu supérieur à celui du nouveau-né, il n'influence pas la cinétique foetale.

Little is known about the major cardiovascular risk factors in HIV-infected as compared to the HIV-uninfected patients in the Democratic Republic of Congo (DR Congo). We determined the prevalence of hypertension, obesity (BMI ≥ 30 kg/m

We conducted a study to evaluate the tolerance of the zidovudine (AZT), lamivudine (3TC) and nevirapine (NVP) combination regimen in HIV-1 patients by a descriptive analytical retrospective study of all HIV-1 patients receiving AZT-3TC-NVP combination between 2008 and 2011. Seventy patients were included. Two thirds of the patients presented at least one side effect (44 cases). The digestive disorders (15 cases) and neuropsychiatric (14 cases) were the most frequent. Epigastralgia (20%), headaches (20%) and arthralgias (13%) were main side effects. A maculo-papular exanthema was noted in three cases. During the follow-up, five patients presented with anemia. No patient presented hepatic cytolysis due to NVP. All the patients followed for more than six months presented a side effect against 29.7% when the duration of treatment was equal to or less than 6 months (p=10(-5)). Most of the side effects due to the association AZT/3TC/NVP are minor. The evaluation of the clinical and biological tolerance must be maintained during all the follow-up.

Objectif. Evaluer l’efficacite du suivi des enfants infectes par le VIH/sida sous traitement antiretroviral (TAR) en milieu rural au Togo. Contexte, population et methodes. Etude retrospective descriptive et analytique menee au centre Luis-Scrosospi de Kouve, de novembre 2008 a novembre 2009, sur les dossiers des enfants sous TAR depuis six mois au moins. Resultats. Notre etude a porte sur les dossiers de 55 enfants (âge moyen de 6 ans et 3 mois, sex-ratio de 0,9). Trente-trois (60 %) avaient une malnutrition aigue severe. Les infections opportunistes et intercurrentes etaient dominees par les infections respiratoires et le paludisme. Au debut du TAR, le nombre moyen de lymphocytes TCD4 etait de 358 cellules/mm 3 et le poids moyen de 12,9 kg. Le taux d’hemoglobine etait inferieur a 8 g/dL dans 31 % des cas. Tous les enfants recevaient chaque mois un kit nutritionnel. Le TAR, donne a 52 enfants, etait l’association stavudine/lamivudine/nevirapine. Le taux de non-observance du traitement durant les douze premiers mois etait de 20 % (11 enfants/55). Le gain ponderal moyen etait de 860 g (inferieur a -3DS), 1 550 g (compris entre -3DS et -2DS) et 1 270 g (compris entre -2DS et -1DS) respectivement a 3, a 6 et a 12 mois de traitement. Le taux de malnutrition aigue severe est passe a 56 %, 47 % et 25 % respectivement a 3, a 6 et a 12 mois. Nous avons note une augmentation du nombre de lymphocytes TCD4 chez 60 % des enfants apres douze mois de traitement. Les principaux effets secondaires etaient les neuropathies peripheriques (29 %) et les cephalees (18 %). Nous avons note huit deces (14 %) au cours du suivi. Conclusion. Le suivi des enfants infectes par le VIH/sida sous TAR est possible en milieu rural au Togo et devrait etre encourage afin d’atteindre les Objectifs du millenaire pour le developpement.

HIV-infected patients by population method. 170 patients on nevirapine-based antiretroviraltherapy were from the ESTHER cohort of the Calmette hospital in Phnom-Penh. 312 patients onefavirenz-based therapy were included in the CAMELIA (ANRS1295–CIPRAKH001) clinical trialconducted in Cambodia. Plasma concentrations of nevirapine and efavirenz were measured byHPLC and UV detection. Median plasma concentrations of nevirapine and efavirenz were 5.7μg/mL and 2.7 μg/mL respectively. Apparent plasma clearances of nevirapine and efavirenz were2.6 L/h and 7.7 L/h respectively. Among demographic, clinical, biological or genetic covariates,genetic polymorphism of CYP2B6 G516T was the only one which was shown to affect theclearance of the 2 drugs. Frequency of the T allele was 34% in this population of South-East Asia., La variabilité de la pharmacocinétique de la névirapine et de l’éfavirenz, deux médicamentsantirétroviraux inhibiteurs non nucléosidiques de la transcriptase inverse du VIH, a été étudiéechez des patients cambodgiens infectés par le VIH par une méthode de pharmacocinétique depopulation. Cent soixante dix patients traités par névirapine faisaient partie de la cohorteESTHER de l’hôpital Calmette de Phnom-Penh et 312 patients co-infectés par le VIH et latuberculose et traités par éfavirenz étaient inclus dans l’essai clinique CAMELIA (ANRS1295–CIPRA KH001) conduit au Cambodge. Les dosages plasmatiques de névirapine et d’éfavirenz ontété réalisés par des méthodes CLHP avec détection UV. Après 18 et 36 mois de traitement, lesconcentrations plasmatiques médianes de la névirapine sont de 5,7 μg/mL. Après 22 et 50semaines de traitement, les concentrations médianes d’éfavirenz sont de 2,7 μg/mL, quel’éfavirenz soit associé (22 semaines) ou non (50 semaines) à la rifampicine. Les clairancesapparentes estimées de la névirapine et de l’éfavirenz sont respectivement de 2,6 L/h et de 7,7L/h. Les variabilités intra et inter individuelles des clairances apparentes sont respectivement de17% et 28% pour la névirapine et 15% et 37% pour l’éfavirenz. Parmi les covariablesdémographiques, biologiques ou génétiques étudiées, seul le polymorphisme génétique duCYP2B6 G516T est significativement associé à la clairance apparente de ces deux médicaments.Ainsi la clairance apparente estimée de la névirapine est de 2,95 L/h, 2,62 L/h et 1,86 L/hrespectivement pour les génotypes CYP2B6 516GG, 516GT, et 516TT. La fréquence de l’allèlemutée T qui code pour une enzyme non fonctionnelle est de 34% dans cette population de 442patients d’Asie du Sud-Est.

HIV-infected patients by population method. 170 patients on nevirapine-based antiretroviraltherapy were from the ESTHER cohort of the Calmette hospital in Phnom-Penh. 312 patients onefavirenz-based therapy were included in the CAMELIA (ANRS1295–CIPRAKH001) clinical trialconducted in Cambodia. Plasma concentrations of nevirapine and efavirenz were measured byHPLC and UV detection. Median plasma concentrations of nevirapine and efavirenz were 5.7μg/mL and 2.7 μg/mL respectively. Apparent plasma clearances of nevirapine and efavirenz were2.6 L/h and 7.7 L/h respectively. Among demographic, clinical, biological or genetic covariates,genetic polymorphism of CYP2B6 G516T was the only one which was shown to affect theclearance of the 2 drugs. Frequency of the T allele was 34% in this population of South-East Asia., La variabilité de la pharmacocinétique de la névirapine et de l’éfavirenz, deux médicamentsantirétroviraux inhibiteurs non nucléosidiques de la transcriptase inverse du VIH, a été étudiéechez des patients cambodgiens infectés par le VIH par une méthode de pharmacocinétique depopulation. Cent soixante dix patients traités par névirapine faisaient partie de la cohorteESTHER de l’hôpital Calmette de Phnom-Penh et 312 patients co-infectés par le VIH et latuberculose et traités par éfavirenz étaient inclus dans l’essai clinique CAMELIA (ANRS1295–CIPRA KH001) conduit au Cambodge. Les dosages plasmatiques de névirapine et d’éfavirenz ontété réalisés par des méthodes CLHP avec détection UV. Après 18 et 36 mois de traitement, lesconcentrations plasmatiques médianes de la névirapine sont de 5,7 μg/mL. Après 22 et 50semaines de traitement, les concentrations médianes d’éfavirenz sont de 2,7 μg/mL, quel’éfavirenz soit associé (22 semaines) ou non (50 semaines) à la rifampicine. Les clairancesapparentes estimées de la névirapine et de l’éfavirenz sont respectivement de 2,6 L/h et de 7,7L/h. Les variabilités intra et inter individuelles des clairances apparentes sont respectivement de17% et 28% pour la névirapine et 15% et 37% pour l’éfavirenz. Parmi les covariablesdémographiques, biologiques ou génétiques étudiées, seul le polymorphisme génétique duCYP2B6 G516T est significativement associé à la clairance apparente de ces deux médicaments.Ainsi la clairance apparente estimée de la névirapine est de 2,95 L/h, 2,62 L/h et 1,86 L/hrespectivement pour les génotypes CYP2B6 516GG, 516GT, et 516TT. La fréquence de l’allèlemutée T qui code pour une enzyme non fonctionnelle est de 34% dans cette population de 442patients d’Asie du Sud-Est.

The purpose of this study was to document epidemiological features, outcomes, and aetiologies of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a teaching hospital in Lomé, Togo.A retrospective study of patients with SJS/TEN treated from January 2002 to April 2009 in a teaching hospital in Lomé was conducted.During the study period, 89 patients were treated for SJS/TEN, i.e., SJS in 76 cases, TEN in 9, and overlapping SJS/TEN in 4. Mean age was 30.3 +/- 13.4 years and sex ratio (M/F) was 0.7. Serological testing for HIV was carried out in 75 patients and was positive in 41 (54.6%) including 36 patients with SJS, 3 with TEN and 2 with overlapping SJS/TEN. A total of 9 patients died including 4 with SJS, 4 with TEN and one with overlapping SJS/TEN. Six of the patients who died were HIV-infected. Complications included blindness in 3 cases, moderate dry eye syndrome in 1, vaginal synechiae in 2, synechiae of labial commeasures in 1, and hypertrophic scars in 1. Antibacterial sulphonamides (50.6%) were the most commonly implicated drugs followed by nevirapine (23.6%), non-steroidal anti-inflammatory drugs (5.6%), and anti-epileptic medications (3.4%).Our results also document the high frequency of nevirapine as a new SJS/TEN cause unrelated to antibacterial sulphonamides. With increasing access to HIV medication in sub-Saharan Africa countries, practitioners should take these data into account for patient monitoring.

Modeling of CD4 cells counts response was performed through a Non-Hierarchical-descendant process with profoundly immunocompromised symptomatic patients under nevirapine or efavirenz-based antiretroviral regimen in Abidjan. Similar CD4 cells count trajectories have been modelled in meta-trajectories linked to patients' classes. Global immunological response is similar between "nevirapine group" and "efavirenz group" but the model showed an internal variation of this response in each group. In the both groups, some variables presented a significant variation between classes: average CD4, CD4 Nadir, CD4 peak and average gain of CD4. In "nevirapine group", these following parameters vary significantly between classes: mean weight, mean haemoglobin count and mean increase in haemoglobin count and sex. It's also important to note that, all meta-trajectories began with distinctive categories of baseline CD4 cells counts. Other explanatory factors must be sought because the characteristics we have chosen to describe patients'classes, are not exhaustive.

The purpose of this study is to analyze the fate of children born to HIV-positive mothers and to determine the impact of feeding options on the HIV status of the children in preventing mother-to-child transmission sites (PMTCT) in Togo. It was a retrospective and descriptive study, focused on medical files of 1042 children of both sexes aged from 0 to 59 months born to HIV-positive mothers and registered in the PMTCT sites between January 2004 and December 2008. Our study was conducted in seven PMTCT sites located in four of the six health regions in the country. We analyzed a total of 1042 medical files in seven PMTCT sites selected. The majority of children were born vaginally (77.4%). Antiretroviral prophylaxis most used in the mothers and/or the children was nevirapine in 86% of the cases. Breastfeeding (49%) was dominated by milk substitutes (50%). Globally, dropout rate was 52.2% (525), with 44.9% (408) at six months and 65.09% (483) at 12 months. At 12 months, 196 of 742 children (26.4%) had their retroviral serology. Among them, we have 5.6% overall rate of HIV infection. The transmission rate in the group of children breastfed was 5.9% (six children infected out of 102) and 8.5% in the group of children fed by formula milk (seven children out of 82). Death occurred in half of the cases (8 of 16) during the first two months of life. Follow-up was the major issue in monitoring children born to HIV-infected mothers. The HIV transmission rate is very high, irrespective of the feeding method.

Taking into account long-term adverse effects of antiretroviral treatment has become a major concern for physicians managing HIV infected patients. More specifically, cardiovascular risk is the fourth cause of death in this population. Nevirapine, when used in antiretroviral naive patients or as a substitution for tritherapy, has constantly proven superior to other combinations for HDL-c lipid disorders. The main metabolic process responsible for this protective effect is the increased A1 apolipoprotein production. International cohort studies such as DAD or SMART suggest that a very limited risk of cardiovascular morbidity might be associated to nevirapine exposure. This data should be considered when choosing antiretroviral treatment, especially for initiation of treatment in patients with cardiovascular risk factors or when substituting for an efficient tritherapy.

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, lamivudinenevirapine) 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.

The aim of this study was to determine the incidence of the side-effects of the fixed dose combination of stavudine/lamivudine/nevirapine (Triomune) during treatment of the HIV infected patients in Togo. It was a multicentric retrospective study carried out from September 2003 to October 2005. We collected data from the medical files of the HIV infected patients using antiretroviral therapy Patients were included in the study if using Triomune and were followed up regularly in an accredited centre of management of HIV infected patients for at least one month. Biological examinations carried out were blood cells count, transaminases, uremia, creatininemia, glycemia and lymphocyte T CD4 cells count. During the period of our study on one sample out of 1000 files of HIV infected patients followed in the medical centres using antiretroviral therapy 297 patients took Triomune. The average age was 36.8 years (range: 5-68 years), 64% were female. The average duration of the antiretroviral therapy of the patients using Triomune was 6 months. Side-effects were noted in 78 cases (26,3%). The main side-effects were: digestive disorders (30 cases; 10%), skin rashes (27 cases; 9%), headaches (19 cases; 6.4%), paresthesias (7 cases; 2.4%). We found neither hepatotoxicity nor lipodystrophy. The majority of skin rashes (63%) had occurred during the first month of treatment, and was severe (stade 3 and 4 of WHO) in 6 cases (22.2%) and consequently justified the stop of nevirapine. The paresthesias had occurred after about 3 months of treatment, they were severe in 2 cases (stade 3 of WHO) justifying consequently the stop of stavudine. The results of this study confirm the low severe side-effects of Triomune during the first six months of treatment.

A retrospective study was conducted during 32 months; from 1 May 2003 to 30 December 2005 in haematology department. The objective of the study was to assess the effectiveness of the anti retroviral therapy 157 patients receiving antiretroviral treatment for at least a twelve month-period and presenting AIDS symptoms based on revised CDC criteria were included. The average number of initial T4 lymphocytes is 133/mm3 (extremes 1 and 385) and the initial plasmatic average viral load, quantified in 96 patients is 214,000 copies (extreme 30,000 et 999,000) The initial antiretroviral combinations were as follows: ZDV or D4T + LMV + NVP (59.2%); ZDV or D4T + LMV + EFV (28.7%), ZDV or D4T + LMV + IDNV (8.9%); ZDV or D4T + DDI + NVP (3.2%). The results of the study are: observance rate during the first 12 months (84%), antiretroviral therapy taken irregularly (10.8%), early submission of therapy (5.2%), weight gain after 24 months: +18 kgs, clinical response globally positive. The immune response is characterised by an average increase of 353/mm3 of CD4 after 24 months. Among 96 patients tested, the plasmatic viral load was undetectable in 71% of cases after a 12 month-follow up. Mild adverse drug effects have been noticed, represented by cutaneous and nervous toxicity anaemia and digestive disorders due to indinavir These therapeutic results confirm the importance of the antiretroviral therapy in the improvement of the quality of life of HIV/AIDS patients but a concern remains on the possible drug resistance still not documented.

Peripheral neuropathies (PN) represent the most common neurological manifestation in patients with HIV infection. Introduction of highly active antiretroviral therapy (HAART) had a significant impact on the epidemiology of HIV-associated neuropathies even in poor-resources countries. HIV-infected patients were followed up over a 2-years period from January 2002 to December 2003. PN was clinically diagnosed based on abnormalities of ankle reflexes or vibratory perception and if patients described pain, paresthesia or numbness. Electromyography was not performed in this study Among the 133 HIV-infected patients treated with HAART 31 patients (23 females and 8 males) with 38.8 of mean age were followed up for PN. 95.5% among them were HIV1-infected. According to the availability of the antiretroviral therapy, 9 patients were treated with protocol A including lamivudine + stavudine + nevirapine, 12 patients with protocol B including combination of stavudine + lamivudine + efavirenz, and 10 patients with protocol C with other combinations of antiretroviral therapies. Average CD4 cell count was 229.3/microl and 60% of the sample had200 CD4 cell counts at the time of diagnosis. PN occurred within 5.6 months from the institution of the HAART and 80% less than 3 months after the beginning of the treatment. Burning feet syndrome was found in 16.1% of the sample. 45.2% of polyneuropathies occurred in late stage of HIV infection (200 CD4/microl). The presence of PN was related to decreased CD4 cells counts and neurotoxic antiretroviral therapy Introduction of HAART has modified the course and the prognosis of HIV infection even in poor resources setting. The incidence of toxic neuropathies is increasing with longer patients' life expectancy and represents a major factor in treatment limitation and the neurological side effects of HAART should be well identified by physicians.

A cross-sectional survey was conducted among 112 HIV positive patients who had received antiretroviral therapy for3 months to assess the efficacy of treatment (viral load400 copies/mL). The median age at enrolment was 36 years, 90% of patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1 PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of the prescribed protocol and the initial clinical and immunological profile. Mean improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The predictors for treatment success were quality of care and KI70%.

The authors report the first case of Stevens-Johnson syndrome which has occurred in a 45 year old patient treated by Triomune containing névirapine. Triomune is used within the context of the African antiretroviral initiative access. It was a mild form whose evolution was favourable when nevirapine was stopped. The prevalence of this affection should increase with the larger use of nevirapine in our countries and the attention of both prescriber and patient must be requested.

Antiretroviral therapy has dramatically changed the natural history of HIV infection. The aim of this study was to evaluate the effectiveness and tolerance of Non Nucleosidic Reverse Trancriptase Inhibitors containing regimens in HIV-1 infection.This is a retrospective chart review of 257 HIV-1 infected patients followed in the infectious clinic ward of fann, from august 1998 to February 2002.Overall 195 patients (75.87%) were on efavirenz and 62 (25.2%) on nevirapine, with a male predominance (sex-ratio = 1.44). Baseline HIV-1 viral load was higher in efavirene group (p = 0.03). The two groups were comparable for immune restoration, tolerance, rate of treatment discontinuation and letality. The viral suppression was greater in efavirenz group at month 6 (p = 0.04).Non nucleosidic reverse transcriptase inhibitor containing regimens are effective and well tolerated. Those results make them suitable for first line therapy in HIV-1-infection.

Several studies have shown a high prevalence of rash induced by nevirapine. However, there is little knowledge about the risk factors associated with nevirapine-induced rash. The aim of this study was to identify risk factors associated with the occurrence of rash during the treatment with nevirapine of HIV-infected patients.A retrospective study was conducted in the dermatology department of Besançon university teaching hospital between November 1998 and September 2001. The study included all HIV-infected patients receiving HAART regimens that included nevirapine. The following data were collected: age, sex, CDC classification of HIV, CD4 and CD8 lymphocyte counts, plasma HIV RNA load, hepatitis B, C and cytomegalovirus serostatus, history of drug allergy, concomitant medication (other antiretroviral drugs, corticosteroids, antihistamines). Univariate analysis was performed using a Chi2 test or Fischer's test and Student's t test. Fischer's test and the Cox proportional hazards model were used in the multivariate analysis.During the study period, 101 HIV-infected patients (74 men and 27 women; mean age: 41.6 +/- 10.3 years) were treated with HAART regimens including nevirapine. Fourteen developed cutaneous drug-reactions attributable to nevirapine (13.86%). We observed 13 cases of maculopapular exanthema and 1 case of DRESS. In the univariate analysis, female gender (p=0.002), plasma HIV RNA load10,000 copies/ml (p=0.05), heterosexual transmission (p=0.002) and abacavir treatment (p=0.05) constituted risk factors associated with rash. In the multivariate analysis, only female gender (p0.0001) and plasma HIV RNA load10,000 copies/ml (p=0.0007) were associated with rash.The results of this study confirm the high frequency of toxidermy associated with nevirapine therapy. The risk factors associated with occurrence of rash due to nevirapine therapy were female gender and plasma RNA10,000 copies/ml. Several studies showed absence of any protective effect of antihistamines and corticosteroids in preventing the cutaneous adverse reactions associated with nevirapine. The identification of risk factors closely associated with nevirapine-induced rash could help physicians determine new strategies for safer use of nevirapine in the HAART regimen.

The combination of zidovudine (AZT) + lamivudine (3TC) twice a day + tenofovir once a day, in HIV-infected, antiretroviral-naive patients leads to the rapid and prolonged reduction in viral load, with good immune response and reasonable tolerance profile. According to the results of the boosted FosAmprenavir solo trial, adherence was simplified by the reduced number of daily administration and tablets (once a day) and hence a decline in virological failure rates. Enfuvirtide, an antiretroviral inhibiting the fusion of the virus membrane and cell, combined with optimal antiviral therapy, leads to virological response in 78% of patients and prolonged for more than 6 months in 33%, with good tolerance. In patients treated with neviparine, the frequency of hepatotoxicity justifies early and rigorous monitoring of the hepatic enzymes, notably in the case of high transaminase levels before initiation of treatment.

CIRCUMSTANCES AND CHARACTERISTICS: The risk of toxiderma is greater in patients infected by the human immunodeficiency virus (HIV). The most common toxidermas are maculopapular exanthema and drug hypersensitivity reactions. These toxidermas are predominantly observed with non-nucleoside reverse transcriptase analogs (nevirapine, efavirenz) and abacavir. Toxiderma has also been observed with other nucleoside reverse transcriptase analogs (zalcitabine) and protease inhibitors. REGARDING SEVERITY: The toxidermas observed are usually benign (maculopapular exanthema) and do not always require suspension of the treatment. However, certain toxidermas (Stevens-Johnson syndrome, Lyell syndrome and drug hypersensitivity syndrome) may be life-threatening and therefore contraindicate the continuation of treatment and also its sudden reintroduction. PREVENTION AND PRACTICAL APPROACH: Several studies have assessed the risk factors for toxiderma induced by nevirapine and hypersensitivity reactions to abacavir. The practical approach varies depending on the drug responsible, the clinical form of the toxiderma and the possible alternatives.

The purpose of this study was to investigate the restoration of immune function in patients given two nucleoside-analogs and one non-nucleoside-analog (nevirapine).The study was carried out in 27 HIV-1-infected patients, starting a treatment with d4T, ddl and nevirapine, included in the VIRGO trial and followed up to 52 weeks.Total CD4 T cells increased as early as the fourth week of treatment (+154/microliter, p0.001) with a gain maintained until week 52 (+201/microliter at week 52). A similar pattern was seen for memory CD4 T cells (+80/microliter at week 4, +110/microliter at week 52). The rise in naive CD4 T cells was slower, strongly significant for week 16 (p0.001) and maximum at week 24 (+105/microliter).In our study, rise in T cells was not correlated with virological response, however increase in total and naive CD4 T cells was correlated with the CD4 count at onset of therapy (p0.05). Our data indicate that patients on d4T-ddl-nevirapine therapy have the same immune restoration as patients given protease inhibitor-based regimens.

Antiviral therapy aims to suppress HIV to undetectable levels, and technology to measure these levels is constantly improved. Chiron 3 and similar tests can now detect viral loads as low as 50 copies. Viral load tests have also been valuable in assessing the effectiveness of antiviral drugs. An alliance of mathematicians and doctors have been trying to estimate the level of viral suppression needed to minimize the development of resistance.

A study called INCAS enrolled 150 treatment-naive subjects. Half of the subjects had CD4+ counts of 370 and a viral load of about 32,000 copies. Subjects were divided into groups that received AZT and Nevirapine, ddI and Nevirapine, or AZT with ddI and Nevirapine. Researchers monitored the subjects for 1 year. Results indicated that subjects who received the triple drug combination had fewer complications and infections.

A study by doctors in Spain found that people taking antiviral therapy may develop higher-than-normal levels of lipids and glucose in their blood, insulin resistance, and body shape changes due to fat redistribution. Switching to Nevirapine (Viramune) from a protease-based regimen reversed these side effects in 6 months, and levels of CD4+ and viral load remained unchanged in most subjects. Although lab measures were improved, body shape did not return completely to its pre-protease shape in any of the subjects.

Nevirapine, a non-nucleoside reverse transcriptase inhibitor, is related to Delavirdine and efavirenz, and was given a conditional Notice of Compliance by Canada's Health Protection Branch. This conditional approval requires that additional data from continuing studies be submitted by the drug manufacturer, Boehringer Ingelheim. Participants in the expanded access program will receive Nevirapine through the end of the year.

Manifestations similar to DRESS syndrome (drug rash with eosinophilia and systemic symptoms) may be induced by nevirapine.Three patients developed skin rash and general signs of liver dysfunction during the first 5 weeks after starting nevirapine. Laboratory tests showed elevated eosinophil counts and signs of inflammation simulating severe infection.The incidence of DRESS syndrome is probably underestimated. No standard treatment has been proposed. In our 3 patients, parenteral corticosteroid therapy was successful, leading to a rapidly favorable clinical course although liver tests took longer to return to normal.

Nevirapine is the first non nucleoside reverse transcriptase inhibitor registered in Belgium and indicated in the treatment of HIV-1 infection. In association with 2 nucleoside analogues, its efficiency is similar to a tritherapy with protease inhibitor, particularly in naive patients with low viral load. It has a good tolerance profile and is easy to take. Studies in progress should permit to widen its indications.

Due to its long half-life (25-30 hours) the once daily administration of nevirapine would appear logical but we do not have data regarding the tolerability and efficacy of this schedule. We have therefore tried to evaluate this schedule in 93 HIV-infected patients beginning a treatment containing nevirapine. The tolerability of once daily nevirapine was similar to the usual schedule with 15% of mucocutaneous allergy. The immunologic and virologic efficacy of once daily nevirapine was confirmed with a mean RNA HIV decrease of 1.4 log, 1.3 log, 1.1 log and 1.3 log at M1, M3, M6 and M9 respectively. The best results were observed in naïve patients. Residual plasma concentration of nevirapine was performed in 35 patients with a mean value of 3.8 mg/l.

Nevirapine is the first member of a new therapeutic class (NNRTI: non nucleoside inhibitors of the reverse transcriptase) in the treatment against human immunodeficiency virus (HIV). In association with two other antiretroviral products, it reduces significantly the viral load and increases the CD4-cells-count, especially in naive patients. Results at six months show that a tritherapy including nevirapine and 2 nucleoside inhibitors of the reverse transcriptase (NRTIs) has a similar efficacy than an association including 1 anti-protease and two NRTIs. Nevirapine is easy to take (1 tablet 2x/day, irrespective of the meals). Its tolerance profile is favourable. The principal side effect is a rash, which can be severe in rare cases.