Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.
Adult ; Allopurinol ; Anti-Bacterial Agents ; Apoptosis ; Child* ; Depressive Disorder, Major ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Female ; Humans ; Keratinocytes ; Nevirapine ; Stevens-Johnson Syndrome* ; Tics ; Valproic Acid

OBJECTIVETo compare the HIV suppression rate after initiating antiretroviral treatment(ART) among AIDS patients at different immunological levels and to analyze the related factors.

METHODSData on AIDS patients initially starting antiretroviral therapy during 2008 and 2013 were collected from Chinese HIV/AIDS integrated control system. All the participants were divided into early treatment group(baseline CD4(+)T cell counts between 351/µl and 500/µl) and conventional treatment group(baseline CD4(+)T cell counts ≤ 350/µl). The rates of comprehensive virologic suppression at different time nodes after the initiation of ART were analyzed accordingly. Unconditional logistic regression model was adopted to examine the factors associated with the failure of viral suppression after 6 months after initiation of ART.

RESULTSA total of 16 103 cases were selected, among which, 1 581 cases were early treatment group, and 14 522 cases were conventional treatment group. A total of 9 428 cases were males, 6 675 cases were females, and the sex ratio was 1.41: 1. The age was 47.2 ± 11.7, and 71.55% (11 522/16 103) of cases were married or cohabiting, 57.22% (9 214/16 103) were transmitted by blood. 81.26% (13 086/16 103) were cures in the township or village treatment institution, and 77.17% (12 426/16 103) received the ART regimen as Stavudine(D4T) or Zidovudine(AZT)+Lamivudine(3TC)+Nevirapine(NVP) or Efevirenz(EFV). After 0.5, 1, 2, 3, 4, 5 and 6 years after the initiation of ART, the rates of virologic suppression in the conventional treatment cohort were 72.6% (3 008/4 144), 73.9% (4 758/6 443), 74.1% (3 641/4 915), 74.9% (2 819/3 766), 76.1% (1 729/2 272) and 78.2% (492/629), respectively. While the rates of viral suppression in the early treatment cohort at the same time nodes were 65.5% (315/481), 65.4% (448/685), 68.8% (223/324), 66.0% (155/235), 71.4% (110/154) and 61% (30/49), respectively, and the differences between the two groups were significant (P < 0.05) except at the fourth year. Non-conditional logistic regression analysis showed that in the conventional treatment group, factors associated with low HIV suppression rate were male (OR = 1.23, 95%CI:1.07-1.42) , longer time interval from confirmed HIV infection to received ART (OR = 1.26, 95%CI:1.16-1.36) , using D4T/AZT+ DDI +NVP/EFV as initial treatment regimen (OR = 3.00, 95%CI:2.26-3.98) and nearly missing doses for 7 days at treatment of six months (OR = 1.97, 95%CI:1.22-3.18) and factors associated with high HIV suppression rate were infected through homosexual transmission route (OR = 0.57, 95%CI:0.35-0.90) and treated in the county level medical institution or above (OR = 0.61, 95%CI:0.50-0.75) . Among early treatment group, cases who received treatment at county level medical institution or above had high HIV suppression rate (OR = 0.43, 95%CI:0.23-0.80) and objects with longer time interval from confirmed HIV infection to receive ART had low HIV suppression rate (OR = 1.43, 95%CI:1.09-1.88).

CONCLUSIONThe viral suppression efficacy among AIDS patients with different baseline immunologic levels after treatment was similarly satisfactory. AIDS cases who received ART at county level medical institution or above had better viral suppression effect and patients with longer time interval from confirmation to treatment had poor HIV suppression effect.

Acquired Immunodeficiency Syndrome ; Anti-HIV Agents ; Benzoxazines ; Female ; HIV Infections ; Health Facilities ; Humans ; Lamivudine ; Male ; Nevirapine ; Stavudine ; Time-to-Treatment ; Treatment Outcome ; Zidovudine

Acquired Immunodeficiency Syndrome ; prevention & control ; transmission ; Anti-HIV Agents ; therapeutic use ; Drug Resistance, Viral ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Nevirapine ; therapeutic use

This study is to investigate the mechanism and action characteristics of 6-chloro-3-methyl-4-(2-methyoxycarbonylthiophene-3-sulfonyl)-3, 4-dihydroquinoxa-lin-2-(1 H)-one (XU07011) against HIV-1 replication. XU07011 anti-HIV activity was tested by using VSVG/HIV pseudotype viral system and confirmed by HIV-1 live viruses' infectious assay. Time of addition was used to test HIV-1 reverse transcription process. RNA-dependent DNA polymerase activity and RNase H activity were tested by using enzyme linked immunoabsorbent assay and fluorescence method. Wild type and nine NNRTIs-resistant reverse transcriptase enzymatic models and cell-based pharmacological models were used to evaluate XU07011 bio-characteristics. The results showed that XU07011 inhibited HIV-1 replication with IC50 of (0.057 +/- 0.01) micromol x L(-1) which was comparable to nevirapine [IC50: (0.046 +/- 0.01) micromol x L(-1)]. Mechanism study data indicated that XU07011 blocked HIV-1 reverse transcription process through acting on reverse transcriptase RNA-dependent DNA polymerase with IC 50 of (1.1 +/- 0.3) micromol x L(-1). The compound showed no effect on RNase H activity. XU07011 exhibited better activities comparing with nevirapine on K103N mutated NNRTIs-resistant HIV-1 strains. This study could provide a theoretical basis for novel anti-HIV reagents development.
Anti-HIV Agents ; chemistry ; pharmacology ; Drug Resistance, Viral ; HEK293 Cells ; HIV-1 ; physiology ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Nevirapine ; pharmacology ; Quinoxalines ; pharmacology ; RNA-Directed DNA Polymerase ; metabolism ; Ribonuclease H ; metabolism ; Thiophenes ; pharmacology ; Virus Replication ; drug effects

BACKGROUNDVirus with nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs) resistant mutations show different evolution tendencies when the anti-viral therapies are interrupted. Understanding the replication fitness of drug-resistant virus is important for the study of the prevalence of drug-resistance. For this purpose, we characterized the replication capacity of HIV-1 virus carrying lamivudine (3TC) or nevirapine (NVP) resistant mutations.

METHODS3TC and NVP resistant variants were induced in vitro by selecting wild type virus in the presence of drugs. For the competitive replication assay, drug-resistant variants were cocultured with wild-type virus in the presence or absence of drugs. The ratios of the viral species were determined over time by using a real-time RT-PCR-based assay.

RESULTS3TC-resistant (M184I mutation) and NVP-resistant (Y181I mutation) virus should be selected in vitro in two different ways. The competitive replication assay showed that the ratio of virus carrying a M184I mutation increased from 98.8%, while the wild type virus decreased to 1.2% after 4 passages in the presence of 3TC; the percentage of virus carrying the Y181I mutation increased to 90.5%, while wild type virus decreased to 9.5% in the presence of NVP. In the absence of drugs, the ratio of virus carrying the M184I mutation decreased to 5.3%, while wild type virus increased to 94.7%; the ratio of virus carrying Y181I increased to 75%, while wild type virus decreased to 25% after 4 passages.

CONCLUSIONSThe NVP-resistant virus is fitter than wild type virus even in the absence of NVP that may be the reason that NNRTIs-resistant virus is spreading quickly.

Cell Line ; Drug Resistance, Viral ; genetics ; HIV-1 ; drug effects ; genetics ; growth & development ; physiology ; Humans ; Lamivudine ; pharmacology ; Mutation ; Nevirapine ; pharmacology ; Reverse Transcriptase Inhibitors ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Virus Replication ; genetics ; physiology

BACKGROUNDLiver injury is one of the most important adverse effects of antiretroviral therapy, leading to therapy changing or discontinuation. Data on liver injury in human immunodeficiency virus-1-infected patients receiving antiretroviral therapy are limited in China. The purpose of this study was to investigate the features of liver injury in human immunodeficiency virus type 1-infected patients receiving non-nucleosides reverse transcriptase inhibitors-based antiretroviral therapy in China.

METHODSSeventy-five patients on antiretroviral therapy containing non-nucleosides reverse transcriptase inhibitors were retrospectively studied. The patients were divided into 2 groups: group 1 (with liver injury, n = 45) and group 2 (without liver injury, n = 30). The features of liver injury were analyzed. The sex, age, baseline CD4 counts, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection, hepatotoxic drug use and nevirapine or efavirenz use were compared between two groups.

RESULTSForty-five patients (60.0%), 31 (68.9%) males and 14 (31.1%) females, aged 12 to 52 years (averaged (39 ± 9) years), experienced at least one episode of liver injury. Forty (53.3%) patients were co-infected with HBV and/or HCV, 42 (56%) patients had concomitant use of antituberculosis drugs or cotrimoxazole, 46 (61.3%) and 29 (38.7%) patients received regimen containing nevirapine and efavirenz, respectively. Grade 1 liver injuries were observed in 26 (57.8%) patients, grade 2 in 16 (35.6%), grade 3 in 2 (4.0%) and grade 4 in 1 (2.2%). Three (6.7%) patients discontinued highly active antiretroviral therapy (HAART) due to liver injury. In group 1, there were 29 (64.4%) patients co-infected with HBV and/or HCV, 32 (71.1%) patients received regimen containing nevirapine, and 30 (66.7%) patients had concomitant use of anti-tuberculosis drugs or cotrimoxazole, respectively, significantly higher than those in group 2 (11 (36.7%), 14 (46.7%) and 12 (40%), respectively; P = 0.018, 0.033, 0.023, respectively). The sex, age, baseline CD4 counts and disease stage were not factors associated with liver injury.

CONCLUSIONSLiver injury associated with HAART containing non-nucleosides reverse transcriptase inhibitors was mild to moderate and those who were co-infected with HBV and/or HCV, had concomitant use of antituberculosis drugs or cotrimoxazole and received a regimen containing nevirapine were prone to liver injury while receiving HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; adverse effects ; Chemical and Drug Induced Liver Injury ; etiology ; Child ; Female ; HIV-1 ; Humans ; Male ; Middle Aged ; Nevirapine ; adverse effects ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; adverse effects

Current in vitro assays for the activity of HIV-RT (reverse transcriptase) require radio-labeled or chemically modified nucleotides to detect reaction products. However, these assays are inherently end-point measurements and labor intensive. Here we describe a novel non-radioactive assay based on the principle of pyrosequencing coupled-enzyme system to monitor the activity of HIV-RT by indirectly measuring the release of pyrophosphate (PP(i)), which is generated during nascent strand synthesis. The results show that our assay could monitor HIV-RT activity with high sensitivity and is suitable for rapid high-throughput drug screening targeting anti-HIV therapies due to its high speed and convenience. Moreover, this assay can be used to measure primase activity in an easy and sensitive manner, which suggests that this novel approach could be wildly used to analyze the activity of PP(i)-generated and ATP-free enzyme reactions.
Anti-HIV Agents ; pharmacology ; Colorimetry ; Diphosphates ; analysis ; metabolism ; Drug Evaluation, Preclinical ; HIV ; drug effects ; enzymology ; HIV Reverse Transcriptase ; analysis ; antagonists & inhibitors ; metabolism ; Humans ; In Vitro Techniques ; Nevirapine ; pharmacology ; Reverse Transcriptase Inhibitors ; pharmacology ; Sequence Analysis, DNA ; Thymine Nucleotides ; metabolism

OBJECTIVETo investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy (HAART).

METHODSFrom October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4+ T cell counts <100/mm3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4+ (naive CD4+ T cell defined by CD45RA+ and CD62L+, memory CD4+ T cell defined by CD45RA-), CD8+ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART (5 different regimes) on 1, 3, 6, 9, and 12 months.

RESULTSBefore HAART mean CD4+ T cell counts were 32 +/- 31 (range 2-91)/mm3, and plasma HIV viral load were 5.07 +/- 0.85 (range 2.04-5.70) log copies/mL. In 1 month's time patients treated with HAART had mean CD4+ and CD8 T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4+ T cells were memory CD4+ T cells, as fol naive CD4+ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months' HAART.

CONCLUSIONThis is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAART.

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; virology ; Adult ; Anti-HIV Agents ; therapeutic use ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; CD4-CD8 Ratio ; CD8-Positive T-Lymphocytes ; immunology ; Didanosine ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lymphocyte Count ; Male ; Middle Aged ; Nevirapine ; therapeutic use ; Stavudine ; therapeutic use ; Viral Load

Anti-HIV Agents ; chemistry ; pharmacology ; Benzoxazines ; Coumarins ; chemistry ; pharmacology ; Delavirdine ; chemistry ; pharmacology ; Drug Resistance, Viral ; HIV Reverse Transcriptase ; drug effects ; HIV-1 ; drug effects ; Humans ; Molecular Conformation ; Molecular Structure ; Nevirapine ; chemistry ; pharmacology ; Oxazines ; chemistry ; pharmacology ; Pyranocoumarins ; Reverse Transcriptase Inhibitors ; chemistry ; pharmacology

OBJECTIVETo investigate the survival rate of AIDS patients after receiving antiretroviral therapy(ART) in Henan province and to determine factors associated with survival status.

METHODSDatabase of AIDS patients receiving ART were downloaded from China Information System for Disease Preventioin and Control-AIDS, retrospective study method was conducted to analyze the information.

INCLUSION CRITERIAinitially received national free ART during January, 2005 to December, 2014; aged 15 years or above; and with relatively complete baseline information and follow-up information. The accumulated survival rate of AIDS patients was calculated by life table method and the influencing factors were analyzed by Cox proportional hazard model.

RESULTSTotal 30 376 AIDS patients were enrolled in this study. During the follow-up period, a total of 3 927 cases died from HIV/AIDS related diseases. The mortality of all patients was 3.2/100 person year. After 1, 5, 10 years after the initiation of ART, the rates of accumulate survival rate were 93.7%, 85.3%, and 78.4%, respectively. Stepwise regression was used to conduct the time multiple factors analysis, the results showed that man (HR=1.28, 95%CI: 1.20-1.37), older age (HR=1.20, 95% CI: 1.16-1.24), others marital status except marrage or cohabitation (HR=1.20,95% CI: 1.12-1.29), more number of symptoms (HR=1.11, 95%CI: 1.07-1.14), initial treatment were main stavudine (D4T) or zidovudine (AZT)+ didanosine(DDI)+ nevirapine (NVP) or efevirenz (EFV) (HR=1.12, 95% CI: 1.04-1.20), missing drug in the past 7 days (HR=18.36,95%CI: 17.08-19.74) among AIDS patients had high mortality risk, homosexuality sexual transmission (HR=0.59, 95% CI: 0.40-0.87), higher baseline count of CD4(+)T lymphocyte (relative to 0-200 cells/µl group, HR (95%CI) were 0.57 (0.53-0.62), 0.43(0.37-0.49), 0.33 (0.27-0.40) in 201-350 cells/µl group, 351-500 cells/µl group, and ≥501 cells/µl group, respectively), higher educations (HR=0.89, 95% CI: 0.83-0.95) had low mortality risk.

CONCLUSIONSurvival rate was higher after initial antiretroviral treatment among AIDS patients in Henan province. AIDS patient will have shorter survival time after antiviral treatment under one or more following conditions: higher age, male, initial treatment with D4T or AZT + DDI + NVP or EFV, lower baseline CD4 (+) T lymphocyte count, ever missed antiviral drugs in past 7 days of latest follow-up.

Acquired Immunodeficiency Syndrome ; drug therapy ; epidemiology ; Anti-Retroviral Agents ; therapeutic use ; China ; epidemiology ; Drug Therapy, Combination ; Female ; Humans ; Lymphocyte Count ; Male ; Nevirapine ; therapeutic use ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stavudine ; therapeutic use ; Survival Analysis ; Survival Rate ; Zidovudine ; therapeutic use