The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.
Asian Continental Ancestry Group* ; Atazanavir Sulfate ; HIV* ; HIV-1* ; Humans ; Humans* ; Protease Inhibitors ; Reverse Transcriptase Inhibitors

For 16 years after the finding of HIV as an agent of AIDS in 1981, HIV therapeutic drugs of reverse transcriptase inhibitors (AZT, ddI, ddC, d4T) and protease inhibitors have been developed. Recent studies also were focused on a combination therapy by using HIV therapeutic drugs or natural compounds. Korean red ginseng (KRG) of natural compounds has been well known as a good reinforcement agent in Asia. The percentage of CD3+CD4+ T cell in nine HIV-infected patients without KRG treatment averaged 17.8% on baseline and decreased 15.8% after 6 months, whereas the percentage of the cell in fifteen HIV-infected patients with KRG treatment averaged 15.3% on baseline and increased up to 18.9% after the same period. The average percentage of CD3+CD8+ T cell of KRG-nontreated and KRG-treated HIV patients increased after 6 months 47.8% to 50.7% and 44.7% to 51.4%, respectively; and the average percentage of B and NK cell in the KRG-nontreated and KRG-treated HIV patients decreased 9.4% to 7.9% and 13.0% to 9.7%, 8.9% to 8.5% and 16.2% to 11.6%, respectively, KRG, therefore, didn't have any effects on the CD3+CD8+ T cell, B cell, and NK cell. However, it seems that KRG has a potential activity for stimulating the
Asia ; HIV ; Humans ; Killer Cells, Natural ; Lymphocyte Subsets* ; Lymphocytes* ; Panax* ; Protease Inhibitors ; Reverse Transcriptase Inhibitors

Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)).
Culture Media ; chemistry ; metabolism ; HIV Protease ; analysis ; HIV Protease Inhibitors ; chemistry ; isolation & purification ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Streptomyces ; chemistry ; metabolism

OBJECTIVEFrequency, type and clinical implications on protease and reverse transcriptase drug resistance mutations were investigated and phylogenetic analysis in antiretroviral drug-naïve AIDS patients was carried out in Henan province.

METHODS45 plasma samples were separated from the anticoagulatory whole blood, from which reverse transcription-polymerase chain reaction technique was used to amplify the partial pol gene. The sequences were analysed for genotypic antiretroviral resistance and phylogenetic relation through landing the websites http://hivdb.stanford.edu and http://hiv-web.lanl.gov, under BioEdit and DNAClub software.

RESULTSPartial pol sequences of 36 samples were successfully amplified. The major mutation rate of resistance to protease was 8.3% (3/36), including types D30A, V32A, G73C and V82A. Minor mutation rate of resistance was 100%, including types of L63PS (36/36), I93L (35/36), V77IL (34/36), A71IVT (10/36) and D60E (2/36). The mutation rate of resistance to reverse transcriptase was 38.9% (14/36). Mutation-scoring and clinical implication clewed drug resistance rates were 5.6% (2/36) and 22.2% (8/36) to protease inhibitors and reverse transcriptase inhibitors respectively, while 1 sample was potentially low-level resistant to all of the protease inhibitors and 3 samples to part of the reverse transcriptase inhibitors. Phylogenetic analysis revealed that the pol gene of 36 samples were highly homologous and having a near relative to B.US.83.RF ACC M17451. 36 samples seemed to have the same infection source while their resistance mutations were not due to drug-resistant virus infection but to the evolving of virus in vivo.

CONCLUSIONMost of the antiretroviral drug-naïve AIDS patients in Henan province were sensitive to the currently available antiviral medicine, but antiviral treatment must be in accordance with the strict procedure and to keep better adherence, to avoid the epidemics caused by drug-resistant virus.

Acquired Immunodeficiency Syndrome ; genetics ; Adult ; Anti-HIV Agents ; pharmacology ; China ; Drug Resistance, Viral ; genetics ; Female ; Genes, pol ; genetics ; Genotype ; HIV Protease ; genetics ; HIV Protease Inhibitors ; pharmacology ; Humans ; Male ; Mutation ; Phylogeny ; RNA-Directed DNA Polymerase ; genetics ; Reverse Transcriptase Inhibitors ; pharmacology

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

AIMTo report the preliminary result of the HIV inhibitor screening based on cheminformatics tools and the traditional Chinese medicine database.

METHODSDatabase search was carried out with saquinavir molecule as a template, further screening was made with docking. Detailed studies using molecular dynamics simulation of 50 ps and 200 ps were made with respect to a potential leading compound, leucovorin.

RESULTSThe leucovorin molecule distinguished from other molecules as a potential drug candidate and is subject to extensive studies. The bonding profile and energy were calculated with MD simulations.

CONCLUSIONOur results could be very helpful when we modify leucovorin or design new inhibitors against HIV.

Anti-HIV Agents ; chemistry ; Databases, Factual ; Drug Design ; Drug Evaluation, Preclinical ; methods ; HIV Protease ; chemistry ; HIV Protease Inhibitors ; chemistry ; Leucovorin ; chemistry ; Ligands ; Medicine, Chinese Traditional ; Models, Molecular ; Molecular Conformation ; Saquinavir ; chemistry

BACKGROUND: The efficacy of antiretroviral therapy (ART) has improved, and the adverse effects of antiretroviral drugs have been reduced. However, these adverse effects still significantly influence patient compliance, increasing the risk of tolerability failure. Therefore, we investigated the adverse effects and tolerability failure causing changes in the first ART regimen, and identified the regimens that were most vulnerable to switching. MATERIALS AND METHODS: We enrolled patients with human immunodeficiency virus (HIV) who commenced their first ART between January 1, 2011 and July 30, 2014. Patients who started their first ART regimen at the Kyungpook National University Hospital were included in the study if they were aged > or =18 years and were followed-up for > or =12 weeks. The primary dependent variable was the duration of treatment on the same ART regimen. We analyzed the maintenance rate of the first ART regimen based on the treatment duration between these groups using survival analysis and log rank test. The frequency of the adverse effects of ART regimens was analyzed by multiple response data analysis. RESULTS: During the investigation period, 137 patients were enrolled. Eighty-one patients were maintained on the initial treatment regimen (59.1%). In protease inhibitor (PI)-based regimen group, 54 patients were maintained on the initial treatment regimen (54/98, 55.1%). In non-nucleoside reverse transcriptase inhibitor (NNRTI)-and integrase inhibitor (II)-based regimen group, 15 (15/26, 57.7%) and 12 (12/13, 92.3%) patients were maintained on the initial treatment regimen, respectively. Adverse effects that induced ART switching included rash (16/35, 45.7%), gastrointestinal discomfort or pain (7/35, 20%), diarrhea (7/35, 20%), hyperbilirubinemia (6/35, 17.1%), headache or dizziness (3/35, 8.5%). Among the treatment regimens, the group receiving an II-based regimen showed the least switching. The group receiving PI-and NRTI-based regimens were most likely to switch due to adverse effects during the early treatment period. However, after about 18 months, switching was rarely observed in these groups. Among the PI drugs, darunavir/ritonavir showed fewer drug changes than atazanavir/ritonavir (P = 0.004, log rank test) and lopinavir/ritonavir (P = 0.010). Among the NNRTI drugs, rilpivirne produced less switching than efavirenz (P = 0.045). CONCLUSION: Adverse effects to ART resulted in about a quarter of patients switching drugs during the early treatment period. II-based regimens were advantageous because they were less likely to induce switching within 18 months of treatment commencement. These findings indicated the importance of considering and monitoring the adverse effects of ART in order to improve adherence.
Diarrhea ; Dizziness ; Exanthema ; Gyeongsangbuk-do ; Headache ; HIV ; Humans ; Hyperbilirubinemia ; Integrases ; Patient Compliance ; Protease Inhibitors ; RNA-Directed DNA Polymerase ; Statistics as Topic

Dyslipidemia, one of the major disadvantages of use of protease inhibitor (PI), is a risk factor for cardiovascular disease in HIV-infected patients receiving antiretroviral treatment. Little is known about the effect of a switch from another PI to unboosted atazanavir (ATV) on the lipid profile. The aim of this study was to evaluate changes in the lipid profile after switching from another PI to either unboosted or boosted ATV in HIV-infected Koreans. We retrospectively collected data on the serum lipid profile at the time of the switch (week 0), and weeks 12 and 24 after the switch, as well as clinical characteristics at week 0 in a total of 27 patients. Triglyceride (TG) showed a significant decrease at weeks 12 and 24 in all patients (196 vs. 174 mg/dL, P=0.048 and 196 vs. 150 mg/dL, P=0.021, respectively). However, these effects were only observed in the unboosted ATV group (N=14; 239 vs. 125 mg/dL, P=0.017 and 239 vs. 87 mg/dL, P=0.021, respectively). For total cholesterol, only the unboosted ATV group at 24 weeks showed a significant decrease (184 vs. 158 mg/dL, P=0.031). No significant changes were observed in LDL- and HDL-cholesterol at weeks 12 and 24 in both the unboosted and boosted ATV groups. These results suggest that changing to unboosted ATV from another PI may ameliorate high TG and total cholesterol in HIV-infected Koreans.
Antiretroviral Therapy, Highly Active ; Atazanavir Sulfate ; Cardiovascular Diseases ; Cholesterol ; Dyslipidemias ; HIV ; Humans ; Oligopeptides ; Protease Inhibitors ; Pyridines ; Retrospective Studies ; Risk Factors

OBJECTIVETo collect background information on drug-resistant HIV-1 strains in various regions before the start of nation-wide antiretroviral therapy in China.

METHODSTwenty percent of the 2,000 blood samples from antiretroviral therapy naive patients collected for the 2nd national HIV molecular epidemiology survey (NHMES) in 2002 were randomly sampled for this study. The entire protease gene and 20-230 amino acids of the reverse transcriptase gene were amplified by PCR from provirus DNA and sequenced. The results were analyzed with HIV db-Drug Resistance Algorithm and genotypic resistance mutations were determined to particular anti-HIV drugs.

RESULTSTotally 164 protease gene sequences and 138 reverse transcriptase gene sequences were obtained from patients; 0.61% of 164 sequences displayed primary resistance mutations in the protease gene, whereas 99.39% carried 1 or more secondary mutations. Genotypic resistance to at least one nucleoside reverse transcriptase inhibitors (NRTI) was present in 5.80%,and resistance to at least one non-nucleo side reverse transcriptase inhibitors (NNRTI) was present in 1.45% of samples.

CONCLUSIONThe prevalence of genotypic drug resistance is very low in drug-naive HIV infected patients from 21 provinces of China tested in this study. Laboratories participated in the NHMES have organized a network to provide drug resistance monitoring service in the current nation-wide antiviral treatment program in China.

Anti-HIV Agents ; therapeutic use ; China ; epidemiology ; Drug Resistance, Viral ; Genotype ; HIV Infections ; drug therapy ; epidemiology ; virology ; HIV Protease ; genetics ; HIV Protease Inhibitors ; therapeutic use ; HIV Reverse Transcriptase ; genetics ; HIV-1 ; genetics ; Humans ; Mutation ; Reverse Transcriptase Inhibitors ; therapeutic use ; Sentinel Surveillance

Atazanavir is a protease inhibitor approved for use in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus infection. Atazanavir and other protease inhibitors can sometimes induce corrected QT prolongation and ventricular arrhythmia. A 40-year-old man with no comorbidities, except human immunodeficiency virus 1 infection, presented with palpitations 3 days after an overdose of 150 caps of atazanavir, with suicidal intent. His initial electrocardiogram showed monomorphic ventricular tachycardia, and hyperbilirubinemia was observed in his initial blood test. Immediately after magnesium sulfate infusion, his ventricular tachycardia was converted into junctional bradycardia with prolonged corrected QT. After 3 days of close observation in the intensive care unit, the corrected QT prolongation and hyperbilirubinemia were normalized.
Adult ; Arrhythmias, Cardiac ; Atazanavir Sulfate* ; Bradycardia ; Comorbidity ; Electrocardiography ; Hematologic Tests ; HIV ; HIV-1 ; Humans ; Hyperbilirubinemia ; Intensive Care Units ; Magnesium Sulfate ; Protease Inhibitors* ; Tachycardia, Ventricular*