To evaluate in vitro anti-HIV efficacies of nucleoside derivatives, MT-4 cell line was infected with HIV-1 and HIV-2 respectively and treated with various compounds and the formerly approved drugs such as AZT, d4T, ddC and ddI. CPE method was used to evaluate their antiviral activity Most dideoxynucleosides, AZT, d4T, ddC and ddI, showed anti-HIV activities against both viruses but no other compounds including anti-herpesvirus drugs did any. Further experiments were carried out to study their inhibitory mechanism of viral adsorption. The results showed no inhibition of syncytium formation due to an interaction between the gp120 expressed in HIV-infected cell surface and CD4 receptor on the uninfected cell surface in the presence of AZT. AZT showed no activity up to 100 microgram/ml. Inhibition of reverse transcriptase (RT) in the presence of AZT-triphosphate was tested by using RT expressed in E. coli and purified and its IC50 was 4.5 nM.
Adsorption ; Cell Line ; Dideoxynucleosides ; Giant Cells ; HIV-1 ; HIV-2 ; Inhibitory Concentration 50 ; RNA-Directed DNA Polymerase ; Stavudine

Nucleoside reverse transcriptase inhibitors (NRTIs), which are used for the treatment of human immunodeficiency virus (HIV) infection have been associated with a wide spectrum of clinical manifestations, including hepatic steatosis, lipodystrophy, myopathy, and lactic acidosis. Such adverse effects are postulated to result from the inhibition of mitochondrial DNA gamma polymerase, which causes the depletion of mitochondrial DNA and eventual the disruption of oxidative phosphorylation. Although cases of severe decompensated lactic acidosis are rare, this syndrome is associated with a high mortality rate. We report upon the first Korean case, of severe lactic acidosis in an acquired immunodeficiency syndrome (AIDS) patient receiving stavudine, an anti-HIV drug.
Acidosis, Lactic/*chemically induced ; Acquired Immunodeficiency Syndrome/*drug therapy ; Adult ; Anti-HIV Agents/*adverse effects/therapeutic use ; Female ; Human ; Sodium Bicarbonate/therapeutic use ; Stavudine/*adverse effects/therapeutic use

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

BACKGROUNDAn zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.

METHODSThis prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.

RESULTSIn terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.

CONCLUSIONAZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.

Adult ; Anti-HIV Agents ; administration & dosage ; adverse effects ; therapeutic use ; Female ; HIV Infections ; drug therapy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stavudine ; administration & dosage ; adverse effects ; therapeutic use ; Zidovudine ; administration & dosage ; adverse effects ; therapeutic use

Adolescent ; Adult ; Anti-HIV Agents ; adverse effects ; Child ; Guideline Adherence ; HIV Infections ; drug therapy ; Humans ; Medical Audit ; Middle Aged ; Practice Guidelines as Topic ; Retrospective Studies ; Safety-Based Drug Withdrawals ; Singapore ; Stavudine ; adverse effects ; World Health Organization ; Young Adult

BACKGROUND: Since the introduction of HAART (Highly Active Anti-Retroviral Therapy), metabolic com- plications have been reported with varying prevalence. We performed a retrospective study to evaluate the incidence and risk factors of metabolic complications arising in Korean HIV/AIDS patients. MATERIALS AND METHODS: 66 HIV positive patients on combination therapy between 1998 June to 2002 June with at least 1 protease inhibitor (PI) or/and Non-nucleoside reverse transcriptase inhibitors (NNRTI) were reviewed. Hyperglycemia was defined as serum glucose >140 mg/dL on 2 or more occasions; diabetes as any random serum glucose >200 mg/dl; hypercholesterolemia as serum cholesterol >240 mg/dL; hypertriglyceridemia as serum triglyceride >200 mg/dL. We used SPSS version 9.0 for statistical analysis. One way ANOVA was used to compare the treatment groups. Multinominal logistic regression analysis was used for risk factor analysis. RESULTS: 66 patients were analyzed and total duration of follow up was 138 patient-years. The incidence of metabolic complication was 20.3%. Incidence of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, and diabetes were 12.3%, 5.8%. 1.4%, 4.3% respectively. On risk factor analysis, factors contributing to the development of metabolic complication were age>35 years (P= 0.020) and baseline serum triglyceride >140 mg/dL (P=0.001). Baseline CD4 count <170/mm3 (P= 0.054) and use of stavudine >6 months (P=0.055) were associated with development of metabolic complications with borderline significance. CONCLUSION: The incidence of metabolic complication among Korean HIV/AIDS patients receiving HAART is 20.3%. Older age and high baseline triglyceride were risk factors for development of metabolic complications.
Antiretroviral Therapy, Highly Active ; Blood Glucose ; CD4 Lymphocyte Count ; Cholesterol ; Follow-Up Studies ; HIV ; Humans ; Hypercholesterolemia ; Hyperglycemia ; Hypertriglyceridemia ; Incidence ; Logistic Models ; Prevalence ; Protease Inhibitors ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; Risk Factors ; Stavudine ; Triglycerides

BACKGROUND: Since the introduction of HAART (Highly Active Anti-Retroviral Therapy), metabolic com- plications have been reported with varying prevalence. We performed a retrospective study to evaluate the incidence and risk factors of metabolic complications arising in Korean HIV/AIDS patients. MATERIALS AND METHODS: 66 HIV positive patients on combination therapy between 1998 June to 2002 June with at least 1 protease inhibitor (PI) or/and Non-nucleoside reverse transcriptase inhibitors (NNRTI) were reviewed. Hyperglycemia was defined as serum glucose >140 mg/dL on 2 or more occasions; diabetes as any random serum glucose >200 mg/dl; hypercholesterolemia as serum cholesterol >240 mg/dL; hypertriglyceridemia as serum triglyceride >200 mg/dL. We used SPSS version 9.0 for statistical analysis. One way ANOVA was used to compare the treatment groups. Multinominal logistic regression analysis was used for risk factor analysis. RESULTS: 66 patients were analyzed and total duration of follow up was 138 patient-years. The incidence of metabolic complication was 20.3%. Incidence of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, and diabetes were 12.3%, 5.8%. 1.4%, 4.3% respectively. On risk factor analysis, factors contributing to the development of metabolic complication were age>35 years (P= 0.020) and baseline serum triglyceride >140 mg/dL (P=0.001). Baseline CD4 count <170/mm3 (P= 0.054) and use of stavudine >6 months (P=0.055) were associated with development of metabolic complications with borderline significance. CONCLUSION: The incidence of metabolic complication among Korean HIV/AIDS patients receiving HAART is 20.3%. Older age and high baseline triglyceride were risk factors for development of metabolic complications.
Antiretroviral Therapy, Highly Active ; Blood Glucose ; CD4 Lymphocyte Count ; Cholesterol ; Follow-Up Studies ; HIV ; Humans ; Hypercholesterolemia ; Hyperglycemia ; Hypertriglyceridemia ; Incidence ; Logistic Models ; Prevalence ; Protease Inhibitors ; Retrospective Studies ; Reverse Transcriptase Inhibitors ; Risk Factors ; Stavudine ; Triglycerides

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 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

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