BACKGROUND: To evaluate the clinical efficacy, safety and tolerance of combination therapy of zidovudine, lamivudine and indinavir in HIV infected patients. METHODS: We reviewed medical records of HIV infected patients who had received combination therapy of zidovudine, lamivudine and indinavir at the Seoul National University Hospital between May 1998 and March 1999. The clinical end point was the time to the development of the opportunistic infection or death. Changes in plasma HIV-1 RNA levels and CD4 cell counts before and after combination treatments were also evaluated. RESULTS: Fifty-two patients were included in this study. Of these, 25 patients (48%) had continued the treatment more than 6 months, whereas 12 patients (23%) were lost to follow-up, and 15 patients (29%) had discontinued the treatment. The causes of discontinuation of the treatment were adverse drug effects in 67% (10/15), economic problem in 20% (3/15) and the development of drug resistance in 13% (2/15). Of the 25 patients who had been treated more than 6 months, 4 patients were excluded because they had not taken the necessary tests at the scheduled time points. Of the 21 evaluable patients, 3 patients (14%) developed opportunistic infections, but no patients died. In seventeen patients (81%), HIV RNA-1 titers decreased below the detectable level by 6 months of treatment. The mean decrease of HIV-1 RNA titer after 6 months of treatment was 2.65 log10 copies/mL. The mean increase of CD4 cell counts was 111 cells/mm3. CONCLUSION: Combination therapy of zidovudine, lamivudine and indinavir was effective in decrease of viral load and increase of CD4 cell counts. Half of the patients could not continue the combination therapy more than 6 months because of the adverse drug effects and/or economical problem.
CD4 Lymphocyte Count ; Drug Resistance ; HIV Infections ; HIV* ; HIV-1 ; Humans ; Indinavir* ; Lamivudine* ; Lost to Follow-Up ; Medical Records ; Opportunistic Infections ; Plasma ; RNA ; Seoul ; Viral Load ; 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

Abacavir is a nucleoside reverse-transcriptase inhibitor that has been approved for use in combination with other retroviral agents in the treatment of HIV infection. Common adverse reactions include headache, fatigue, nausea, and rash. A fatal hypersensitivity reaction may occur in 5% of patients receiving abacavir; therefore, screening for HLA-B5701 should be performed before starting abacavir. Alopecia areata (AA) is infrequently reported in HIV-infected patients. Certain underlying conditions have been associated with AA, including a decreased CD4:CD8 ratio related to the progression of HIV infection, some opportunistic infections, and syphilis. Several antiretroviral drugs, such as zidovudine, indinavir, indinavir/ritonavir, lopinavir/ritonavir, and atazanavir/ritonavir have been implicated in the development of AA. At present, the occurrence of AA has not been associated with abacavir use. We cannot exclude that the use of abacavir and the development of AA could be coincidental. Nevertheless, patients given abacavir should be monitored for hair loss and the drug discontinued promptly if such signs appear.
Alopecia ; Alopecia Areata* ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Fatigue ; Hair ; Headache ; HIV Infections ; Humans ; Hypersensitivity ; Indinavir ; Mass Screening ; Nausea ; Opportunistic Infections ; Syphilis ; 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/AIMS: The introduction of highly active antiretroviral therapy (HAART) has significantly modified the course of HIV infection. However, the HAART regimens, and especially those including protease inhibitors (PIs), have been shown to cause diabetes mellitus. We evaluated the incidence and clinical manifestations of HIV-infected Koreans who received HAART and the risk factors for diabetes mellitus in those patients. METHODS: We conducted a retrospective cohort study and a case-control study to evaluate the clinical manifestations, the incidence and the risk factors for diabetes mellitus in 215 HIV-infected patients who were on HAART at Yonsei University College of Medicine from 1991 to 2006. RESULTS: 215 patients were analyzed and the total duration of follow up was 1079 person-years. The incidences of diabetes mellitus and impaired fasting glucose were 1.39 case/100person-years and 6.02 case/100person-years. Most of the cases were non-obese type II diabetes and these patients showed insulin resistance and impaired beta cell function. On the risk factor analysis, the factors contributing to the development of diabetes were age, a decrease of the viral load and indinavir use. CONCLUSIONS: In our study, the incidence of diabetes among Korean HIV-positive patients on HAART was 1.39case/100person-years. Age, a decrease of the viral load and indinavir use were the risk factors for development of diabetes mellitus.
Acquired Immunodeficiency Syndrome ; Antiretroviral Therapy, Highly Active ; Case-Control Studies ; Cohort Studies ; Diabetes Mellitus ; Fasting ; Follow-Up Studies ; Glucose ; HIV ; HIV Infections ; Humans ; Incidence ; Indinavir ; Insulin Resistance ; Protease Inhibitors ; Retrospective Studies ; Risk Factors ; Viral Load

BACKGROUND: Renal disease is one of the leading causes of morbidity and mortality among people infected with human immunodeficiency virus (HIV). However, there are very few published studies about renal insufficiency in HIV-infected persons in Asia, especially in South Korea. MATERIALS AND METHODS: A cross-sectional study was performed to investigate the prevalence and risk factors of renal insufficiency, defined as <60 mL/min/1.73 m², in subjects in the Korea HIV/AIDS Cohort Study enrolled from 19 institutions between December 2006 and July 2013. Data at entry into the cohort were analyzed. RESULTS: Of 454 enrolled subjects, 24 (5.3%) showed renal insufficiency at entry into the cohort. The mean age of patients in the renal insufficiency group was 5.28 years and the majority were male subjects (91.7%). All the patients were receiving antiretroviral agents, mostly protease inhibitor-based regimens (76.4%), for an average of 19 months. In univariate analysis, older age (P = 0.002), diabetes mellitus (DM) (P = 0.0002), unknown route of transmission (P = 0.007), and taking indinavir (P = 0.0022) were associated with renal insufficiency. In multivariable analysis, older age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.03–1.12, P = 0.002], DM [OR 3.03, 95% CI 1.17–7.82, P = 0.022], unknown route of transmission [OR 6.15, 95% CI 1.77–21.33, P = 0.004], and taking indinavir [OR 3.07, 95% CI 1.17–8.05, P = 0.023] were independent risk factors of renal insufficiency. CONCLUSION: The prevalence of renal insufficiency in HIV-infected subjects in this study was relatively low, similar to that in other countries. Aging, DM, and taking indinavir were significantly associated with decreased glomerular filtration rate. Furthermore, unknown route of transmission was an independent risk factor, which was interpreted as a reflection of patient compliance. Further studies on the incidence and risk factors of renal insufficiency during HIV infection using follow-up cohort data are necessary.
Aging ; Anti-Retroviral Agents ; Asia ; Cohort Studies* ; Cross-Sectional Studies ; Diabetes Mellitus ; Follow-Up Studies ; Glomerular Filtration Rate ; HIV ; HIV Infections ; Humans ; Incidence ; Indinavir ; Korea* ; Male ; Mortality ; Patient Compliance ; Prevalence* ; Renal Insufficiency* ; Risk Factors*

BACKGROUNDThe incidence of HIV-1-related infection diseases and the mortality of AIDS have dramatically decreased since highly active antiretroviral therapy began to be used clinically in China in 1999. And we initiated a second clinical trial using a combination of Efavirenz and Indinavir to observe the effects of the immunoreaction.

METHODSTwenty patients with laboratory-confirmed chronic HIV-1 infection were recruited. Blood samples were collected initially and during the weeks after initiation of treatment. Within 48 hours of blood sampling, peripheral blood plasma and mononuclear cells were separated using routine methods. HIV-1 viral load was measured in thawed plasma samples. Within 48 hours of peripheral blood sampling, CD4(+) and CD8(+) T cell subsets were enumerated.

RESULTSThe drug regimen was efficient in reducing HIV-1 plasma viral load and increasing total CD4(+) T cell counts. The percentage of CD4(+) and CD8(+) T cell subsets expressing CD38 and HLA-DR activation markers was positively correlated with plasma viral load and tended to normalize.

CONCLUSIONSThe combination of Efavirenz and Indinavir was generally well tolerated and efficient at reducing HIV-1 RNA. Furthermore, the treatment improved the immunological function.

ADP-ribosyl Cyclase ; blood ; ADP-ribosyl Cyclase 1 ; Adult ; Aged ; Anti-HIV Agents ; administration & dosage ; Antigens, CD ; blood ; Benzoxazines ; CD4-CD8 Ratio ; Chronic Disease ; Drug Therapy, Combination ; Female ; HIV Infections ; drug therapy ; immunology ; virology ; HIV Protease Inhibitors ; administration & dosage ; HIV-1 ; HLA-DR Antigens ; blood ; Humans ; Indinavir ; administration & dosage ; Male ; Membrane Glycoproteins ; Middle Aged ; Oxazines ; administration & dosage ; Viral Load

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.
Animals ; Anti-HIV Agents ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Drug Synergism ; HIV Reverse Transcriptase ; metabolism ; HIV-1 ; drug effects ; enzymology ; Humans ; Immune Sera ; pharmacology ; Indinavir ; pharmacology ; Lethal Dose 50 ; Male ; Mice ; Pyranocoumarins ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Reverse Transcriptase Inhibitors ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Zidovudine ; pharmacology