To investigate resistance to lamivudine (3TC), we examined the incidence of M184V in 20 HIV-1 patients treated with 3TC for 13.1 +/- 9 months. Fourteen of 20 patients had been exposed to zidovudine (ZDV) or didanosine (ddl) prior to 3TC therapy. Nested PCR targeting to reverse transcriptase (RT) and direct sequencing were performed for peripheral blood mononuclear cells sampled serially. There were resistance mutations to ZDV in at least 9 patients at baseline, although there was no resistance mutation to 3TC. We could detect M184V in 6 (30%) out of 20 patients. The incidence of M184V increased as the duration of therapy prolongs (13% in samples<12 months; 47% in samples gtoreq 12 months). The frequency of mutation M184V was higher in patients with previous mutation to ZDV than in patients with wild type. Resistance mutation was not detected in 7 patients. This study shows that resistance to 3TC tends to develop rapidly in patients with baseline mutations or two drugs combination therapy than in those treated simultaneously with triple drugs. This report is the first on resistance to 3TC in Korean AIDS patients.
Didanosine ; HIV-1* ; Humans ; Incidence ; Lamivudine* ; Polymerase Chain Reaction ; RNA-Directed DNA Polymerase ; Zidovudine

PURPOSE: Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected individuals. However, adverse effects and long term safety in Koreans are hardly known. We evaluated the incidence of adverse effects of various antiretroviral drugs in Koreans, and difference among races was also studied. METHODS: One hundred and twenty six Koreans with HIV infection and AIDS treated with antiretroviral drugs at Yonsei University College of Medicine from 1992 to 2002 were investigated. We analyzed the prevalence of adverse effects of various drugs. RESULTS: The mean age of subjects at initial treatment was 34.4 8.3 years. One hundred and twelve subjects were male, and 14 subjects were female. Adverse effects were found in 40 subjects (33.3%) out of 120 subjects who received zidovudine. The prevalence of adverse effects of didanosine and indinavir were 48.3% (14 out of 29 subjects) and 57.9% (66 of 114 subjects), respectively. Frequent toxicities of the subjects who received zidovudine were bone marrow suppression (13.3%), followed by gastrointestinal intolerance (11.7%), headache (4.2%), and hepatic dysfunction (2.5%). Frequent toxicities of the subjects who received didanosine were gastrointestinal intolerance (24.1%), followed by diarrhea (13.8%), rash (3.4%), peripheral neuropathy (3.4%), and pancreatitis (3.4%). Adverse effects of indinavir were as follows: hyperbilirubinemia (37.7%), flank pain (21.1%), gastrointestinal intolerance (6.1%), and lipodystrophy (5.3%). The main adverse effect of efavirenz was impaired concentration (27.3%). The overall incidence of adverse effects from antiretroviral drugs was 64.3% (81 out of 126 subjects) in HIV-infected Koreans. Change of antiretroviral regimens was inevitable in 36 subjects (28.6%). In most cases, the subjects recovered from adverse effects by conservative management. CONCLUSION: Clinicians should be aware of toxicity profiles in various races in the management of long term treatment with antiretroviral drugs, since the toxicity hazards of these drugs may easily outshadow the success of antiretroviral therapy.
Bone Marrow ; Continental Population Groups ; Diarrhea ; Didanosine ; Exanthema ; Female ; Flank Pain ; Headache ; HIV ; HIV Infections ; Humans ; Hyperbilirubinemia ; Incidence ; Indinavir ; Lipodystrophy ; Male ; Pancreatitis ; Peripheral Nervous System Diseases ; Prevalence ; Zidovudine

PURPOSE: Antiretroviral toxicity is an increasingly important issue in the management of HIV-infected individuals. However, adverse effects and long term safety in Koreans are hardly known. We evaluated the incidence of adverse effects of various antiretroviral drugs in Koreans, and difference among races was also studied. METHODS: One hundred and twenty six Koreans with HIV infection and AIDS treated with antiretroviral drugs at Yonsei University College of Medicine from 1992 to 2002 were investigated. We analyzed the prevalence of adverse effects of various drugs. RESULTS: The mean age of subjects at initial treatment was 34.4 8.3 years. One hundred and twelve subjects were male, and 14 subjects were female. Adverse effects were found in 40 subjects (33.3%) out of 120 subjects who received zidovudine. The prevalence of adverse effects of didanosine and indinavir were 48.3% (14 out of 29 subjects) and 57.9% (66 of 114 subjects), respectively. Frequent toxicities of the subjects who received zidovudine were bone marrow suppression (13.3%), followed by gastrointestinal intolerance (11.7%), headache (4.2%), and hepatic dysfunction (2.5%). Frequent toxicities of the subjects who received didanosine were gastrointestinal intolerance (24.1%), followed by diarrhea (13.8%), rash (3.4%), peripheral neuropathy (3.4%), and pancreatitis (3.4%). Adverse effects of indinavir were as follows: hyperbilirubinemia (37.7%), flank pain (21.1%), gastrointestinal intolerance (6.1%), and lipodystrophy (5.3%). The main adverse effect of efavirenz was impaired concentration (27.3%). The overall incidence of adverse effects from antiretroviral drugs was 64.3% (81 out of 126 subjects) in HIV-infected Koreans. Change of antiretroviral regimens was inevitable in 36 subjects (28.6%). In most cases, the subjects recovered from adverse effects by conservative management. CONCLUSION: Clinicians should be aware of toxicity profiles in various races in the management of long term treatment with antiretroviral drugs, since the toxicity hazards of these drugs may easily outshadow the success of antiretroviral therapy.
Bone Marrow ; Continental Population Groups ; Diarrhea ; Didanosine ; Exanthema ; Female ; Flank Pain ; Headache ; HIV ; HIV Infections ; Humans ; Hyperbilirubinemia ; Incidence ; Indinavir ; Lipodystrophy ; Male ; Pancreatitis ; Peripheral Nervous System Diseases ; Prevalence ; Zidovudine

BACKGROUND: Antiretroviral combination therapy with one protease inhibitor and two reverse transcriptase inhibitors is profoundly suppressive of HIV replication. To determine the efficacy and safety of the triple combination therapy in persons with HIV infection in Korea, we analyzed the response of therapy in terms of immunity and viral load. METHODS: Ten persons with HIV infection, who were treated with triple combination therapy at least 12 months at Yonsei University College of Medicine from 1997 to 1999 were studied. The triple combination therapy regimen consisted of two reverse transcriptase inhibitors (zidovudine or didanosine, lamivudine) and one protease inhibitor (indinavir). We analyzed the levels of HIV RNA, CD4+ cell counts, beta2MG, and p24Ag before and after treatment. Adverse drug reactions during therapy were described. RESULTS: The mean age of patients at treatment was 38.7 years. Nine patients were male, and 1 patient was female. Six patients received triple combination therapy as initial treatment, while 4 patients received it as re-treatment. The mean level of HIV RNA was 129,222 copies/mm3 before treatment. RNA level decreased to less than 500 copies/mm3 (non-detectable range) at 1 month in 7 of 10 patients, at 12 months in 9 of 10 patients. The mean CD4+ cell counts was 206/mm3 before treatment, and 376/mm3 after 12 months treatment. The beta2MG decreased to 2.7 mg/L from 2.8 mg/L after 12 months of treatment. The p24Ag was positive in 3 of 10 patients and negative in all of the patients at 3 months treatment. Mild hyperbilirubinemia (5 cases) was the most frequent adverse reaction followed by flank pain (3 cases), skin rash (2 cases), abdominal discomfort (2 cases), and mild elevation of AST/ALT (1 case). CONCLUSION: The triple combination therapy in HIV infection appeared to be generally well tolerated, and was able to profoundly sustain suppression of HIV replication.
CD4 Lymphocyte Count ; Didanosine ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Female ; Flank Pain ; HIV Infections ; HIV* ; Humans* ; Hyperbilirubinemia ; Korea ; Male ; Protease Inhibitors ; Reverse Transcriptase Inhibitors ; RNA ; Viral Load ; Zidovudine

This study is to establish a cell-based pharmacological model targeting HIV-1 replication for compounds screening and to screen compounds randomly selected from compounds library by using this pseudotyped viral system. The cell-based HIV-1 replication pharmacological model was set up by HIV-1 core packed with vesicular stomatitis virus glycoprotein. The level of HIV-1 replication was presented by reporter genes expression (luciferase activity or percentage of GFP positive cells). When a compound has inhibitory effect on VSVG/HIV model, VSVG/MLV model would be used to test for specificity. Vesicular stomatitis virus glycoprotein can efficiently mediate HIV core into a wide range of host cells. Expression level of reporter genes showed dose-dependent manner with virion dilution. Among 500 compounds, three compounds dose-dependently inhibit HIV-1 replication, but not MLV replication. VSVG/HIV pseudotyped viral system can be used as a pharmacological model for HIV-1 replication inhibitor screening. Compounds 2-methylthio-5-(4-methylbenzo)amido-l,3,4-thiadiazole, N-(3-hydroxyphenyl)-2-(4-isobutylphenyl) propionamide, and N-(4-picolyl)-4-methylbenzenesulfonamide can specifically inhibit HIV-1 replication with IC50 of 1.92, 5.38, and 3.39 micromol L(-1) respectively.
Anti-HIV Agents ; pharmacology ; DNA Replication ; drug effects ; Didanosine ; pharmacology ; Drug Evaluation, Preclinical ; methods ; Genes, Reporter ; drug effects ; genetics ; HIV-1 ; drug effects ; physiology ; Humans ; Lamivudine ; pharmacology ; Pseudocowpox Virus ; Tumor Cells, Cultured ; Virus Replication ; drug effects ; Zidovudine ; pharmacology

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; virology ; Adolescent ; Adult ; Antiretroviral Therapy, Highly Active ; adverse effects ; CD4 Lymphocyte Count ; Child ; Didanosine ; administration & dosage ; Female ; HIV-1 ; Humans ; Immunophenotyping ; Male ; Middle Aged ; Nevirapine ; administration & dosage ; RNA, Viral ; blood ; Stavudine ; administration & dosage ; T-Lymphocytes ; immunology

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

OBJECTIVE: To evaluate the long-term efficacy and safety of nevirapine (NVP)-based regimens for HIV-infected Chinese patients in routine clinical practice. METHODS: From October 2002 to May 2004, 57 HIV-1-infected patients commenced highly active antiretroviral therapy (HAART), and were followed to December 2008. They originally received 2 nucleoside reverse transcriptase inhibitors (NRTIs) and nevirapine. HIV RNA levels, T lymphocyte subsets and safety were assessed. Blood routine test and main laboratory parameter changes were traced. If apparent side effects or virological failure appeared we would, if necessary, terminate the therapy or change the regimen. RESULTS: Of the 57 subjects, 34 were followed-up for more than 4 years. After 5-6 years, 63.3% of the subjects (19/30) had HIV RNA levels<50 copies/microL, and the median increase in CD4(+) cell count from the baseline was 329 cells/microL. The mean decrease in CD8(+) cell count was 128 cells/microL. At the same time, the CD4(+) CD45RA+CD62L cell count and CD4(+)CD45RO(+) cell gradually increased, and the counts of CD8(+)CD38(+) cell declined gradually. These changes are apparent 2 years after HAART. The increase rate slowed down after 2 years. But they did not recover completely as well as healthy people at year 6. About 56% (32/57) of HIV-infected patients developed various drug-related side effects. The most common was gastrointestinal side effect, followed nervous disorder, baldness, and rashes, mostly happened in 6 months. Gamma-GT increased occurred in 29.8% of patients (17/57), and serum cholesterol and triglyceride elevated in 26.3% of the patients (15/57). Six patients developed lipodystrophy, mainly in female patients, and 25 patients showed abnormal blood picture and liver function, renal function changes and amylase elevation. Grade 3-4 adverse events occurred in 3 cases (2 peripheral neuropathy, and 1 suspected lactic acidosis). One subject experienced grade 3 rashes. CONCLUSION Antiretroviral therapy with NVP-based regimens is safe and effective by suppressing HIV viremia and producing continued CD4 cell increases in subjects with HIV or AIDS for 6 years.
Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; Antiretroviral Therapy, Highly Active ; adverse effects ; methods ; CD4 Lymphocyte Count ; China ; Didanosine ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; HIV Infections ; drug therapy ; virology ; HIV-1 ; drug effects ; isolation & purification ; Humans ; Male ; Middle Aged ; Nevirapine ; administration & dosage ; adverse effects ; Reverse Transcriptase Inhibitors ; administration & dosage ; adverse effects ; Stavudine ; administration & dosage ; adverse effects ; Treatment Outcome ; Viral Load ; Young Adult