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International Journal of MCH and AIDS 2021Over the past 15 years, there have been three major updates to the South African national guidelines for the management of human immunodeficiency virus (HIV) in...
BACKGROUND AND OBJECTIVE
Over the past 15 years, there have been three major updates to the South African national guidelines for the management of human immunodeficiency virus (HIV) in children. The purpose of this study is to describe the clinical characteristics of children who were initiated on antiretroviral therapy (ART) in Bloemfontein, South Africa, following these national treatment guidelines.
METHODS
Clinical information during initiation of ART in children aged 0-13 years was obtained from five HIV clinics in Bloemfontein from 2004 to 2019 as part of the establishment of an antiretroviral (ARV) pediatric registry at the University of the Free State. Data were analyzed for patient demographics, clinical presentation (World Health Organization (WHO) HIV-staging, growth rate and comorbid conditions), types of investigations done, and medicines prescribed.
RESULTS
The number of children initiated on ART increased from 168 in the period 2004-2009 to 349 (107.8%) in 2010-2014, and then dropped to 162 in the period 2015-2019. The increase in 2010-2014 was mainly in the <2 years age group by 54.8%, and in the 5 to 10 years age group by 344.4%. In the same period, the number of children with severe illness (WHO HIV-stage 4) decreased by 20.7%, while those with mild to moderate illness (WHO HIV-stage 2 and 3) increased by 17.3%. HIV infection was more severe in children under two years as more patients in this age group presented with WHO HIV-stages 3 and 4, severe underweight (below 3 percentile), severely suppressed CD4 count (< 25%), and a high viral load (> 1000 copies/ml). There was increased use of ABC/3TC/LPVr in the < 3-year age group and ABC/3TC/EFV in the > 3-year age group. There was reduced use of the stavudine and other regimens.
CONCLUSION AND GLOBAL HEALTH IMPLICATIONS
More children were started on ART and safer ARV drugs. Children under 2 years were the most debilitated by HIV, and there was an increase in HIV prevalence among children > 5 years. New strategies for the prevention and management of HIV among children in these two age groups are needed.
PubMed: 34290903
DOI: 10.21106/ijma.471 -
Biomolecules Jun 2021Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the...
Drugs targeting DNA and RNA in mammalian cells or viruses can also affect bacteria present in the host and thereby induce the bacterial SOS system. This has the potential to increase mutagenesis and the development of antimicrobial resistance (AMR). Here, we have examined nucleoside analogues (NAs) commonly used in anti-viral and anti-cancer therapies for potential effects on mutagenesis in , using the rifampicin mutagenicity assay. To further explore the mode of action of the NAs, we applied deletion mutants, a peptide inhibiting Pol V (APIM-peptide) and metabolome and proteome analyses. Five out of the thirteen NAs examined, including three nucleoside reverse transcriptase inhibitors (NRTIs) and two anti-cancer drugs, increased the mutation frequency in by more than 25-fold at doses that were within reported plasma concentration range (Pl.CR), but that did not affect bacterial growth. We show that the SOS response is induced and that the increase in mutation frequency is mediated by the TLS polymerase Pol V. Quantitative mass spectrometry-based metabolite profiling did not reveal large changes in nucleoside phosphate or other central carbon metabolite pools, which suggests that the SOS induction is an effect of increased replicative stress. Our results suggest that NAs/NRTIs can contribute to the development of AMR and that drugs inhibiting Pol V can reverse this mutagenesis.
Topics: Antineoplastic Agents; Antiviral Agents; DNA-Directed DNA Polymerase; Escherichia coli Proteins; Microbial Sensitivity Tests; Mutagenesis; Nucleosides; Stavudine
PubMed: 34198819
DOI: 10.3390/biom11060843 -
The Pan African Medical Journal 2021incidence of adverse drug reactions (ADR) associated with antiretroviral therapy (ART) was higher in developing countries. In two teaching hospital in Ethiopia:...
Predictors of adverse drug reaction among adult HIV-infected patients on antiretroviral therapy in government hospitals of Kaffa Zone, Ethiopia; November 2018: a retrospective cohort.
INTRODUCTION
incidence of adverse drug reactions (ADR) associated with antiretroviral therapy (ART) was higher in developing countries. In two teaching hospital in Ethiopia: Debremarkose 23% and Yirgalem 73.2% of study participants reported at least one ADR. Since there was limited information about ADR in the study area; we aimed to determine its incidence-rate and predictors.
METHODS
we conducted retrospective cohort study using medical records of HIV-infected patients enrolled on ART between 2006 and 2017 in government hospitals of Ethiopia. ADR was defined as report of at least one unwanted response to ART. We run descriptive and cox regression analysis (CRA).
RESULTS
incidence-rate of ADR was 4.1 per 100 person-years (py). Hazards of ADR among patients living at rural was almost two times than at urban; [Adjusted hazard ratio (AHR): 1.94(95% (CI): 1.18, 3.20)]. Stavudine (D4T)-Lamivudine (3TC)-Nevirapine (NVP) had about two times [AHR: 1.78(95%CI: 1.03, 3.08)], Zidovudine(AZT)-3TC-NVP had about two times [AHR: 2.34 (95%CI: 1.20, 4.57)], D4T-3TC-Efaviranze(EFV) had about three times [AHR: 2.86(95%CI: 1.38, 5.95)] and AZT-3TC-EFV had about two times [AHR: 2.16(95%CI: 1.21,3.90)] hazards of ADR than Tenofovir(TDF) based regimens. Being WHO clinical stage III had about two times hazard of ADR [AHR: 2.46 (95%CI: 1.22, 4.95)] and IV had about four times hazard of ADR [AHR: 4.32 (95%CI: 1.88, 9.93)] than stage I.
CONCLUSION
risk of ADR was higher among adult HIV-infected patients on ART living in rural, WHO clinical stage III and IV, and patients on AZT and D4T based regimen. AZT should not be given as an alternative treatment, increase access of TDF regimens.
Topics: Adolescent; Adult; Anti-HIV Agents; Cohort Studies; Ethiopia; Female; HIV Infections; Hospitals, Public; Humans; Incidence; Male; Retrospective Studies; Rural Population; Urban Population; Young Adult
PubMed: 33995787
DOI: 10.11604/pamj.2021.38.181.19915 -
Revista Do Instituto de Medicina... 2021HIV-infected patients are at high risk for developing critical diseases, including opportunistic infections (OI), with consequent admission in intensive care units...
HIV-infected patients are at high risk for developing critical diseases, including opportunistic infections (OI), with consequent admission in intensive care units (ICU). Renal disfunctions are risk factors for death in HIV/AIDS patients, and survival rates in patients undergoing hemodialysis are smaller than the ones observed in the general population. In this context, this study aimed to investigate death-related factors in HIV/AIDS patients in an intensive care setting. This is a retrospective cross-sectional study performed through the analysis of medical records from 271 HIV/AIDS-diagnosed patients hospitalized in an intensive care unit of an infectious disease hospital, in Fortaleza, Ceara State, Brazil. Patients were divided into two groups: those who underwent dialysis during hospitalization and those who did not. Clinical and demographic parameters that could be associated with death were evaluated. Results indicated a prevalence of death of 19.1% (CI 95%: 14.8-24.3). The median age of patients was 47 years, with a male predominance (71.3%). The main causes of admission were pulmonary tuberculosis (16.9%), followed by neurotoxoplasmosis (14.9%). In the bivariate analysis, for those that did not undergo dialysis, age, fever, dyspnea, oliguria, disorientation, kidney injury, use of lamivudine and efavirenz, length of hospitalization, CD4 count, WBC count, platelet count, urea, sodium and LDH levels were the associated variables. In those who needed dialysis, the use of stavudine, abacavir and ritonavir, and the length of hospitalization were associated factors. Renal toxicity by the antiretroviral agents and length of hospitalization increased the risk of death among HIV patients under dialysis.
Topics: Brazil; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; HIV Infections; Humans; Intensive Care Units; Male; Middle Aged; Renal Dialysis; Retrospective Studies
PubMed: 33909847
DOI: 10.1590/S1678-9946202163033 -
Biochemical Pharmacology Mar 2021Since the 1950s, great efforts have been made to develop antiviral agents against many infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus... (Review)
Review
Since the 1950s, great efforts have been made to develop antiviral agents against many infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and varicella-zoster virus (VZV). Among the list of nearly 106 antiviral agents approved in the past five decades, Prof. Erik De Clercq has contributed to the development of 7 antiviral drugs: tenofovir disoproxil fumarate (Viread®) for HIV and HBV treatment, tenofovir alafenamide (Vemlidy®) for HIV and HBV treatment, brivudine (Zostex®) for HSV-1 and VZV treatment, valacyclovir (Valtrex®) for HSV and VZV treatment, adefovir dipivoxil (Hepsera®) for HBV treatment, stavudine (Zerit®) for HIV treatment, and cidofovir (Vistide®) for treating HCMV retinitis in AIDS patients. In addition to the above antiviral drugs, his contributions include two anti-cancer drugs: rabacfosadine (Tanovea®-CA1) for canine lymphoma and plerixafor (Mozobil®) for multiple myeloma and non-Hodgkin's lymphoma. These achievements are driven by his life-long passions for antiviral research and successful collaborations worldwide. To honor the 80th birthday of Prof. Erik De Clercq, this study highlights his scientific achievements and the importance of life-long passions and collaborations in the success of antiviral research and drug development.
Topics: Anniversaries and Special Events; Antiviral Agents; Biomedical Research; Drug Development; Faculty; HIV Infections; Hepatitis C; Humans; Male
PubMed: 33617841
DOI: 10.1016/j.bcp.2021.114485 -
Molecules (Basel, Switzerland) Feb 2021Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV),... (Review)
Review
Nucleoside and nucleotide analogues are essential antivirals in the treatment of infectious diseases such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (HCMV). To celebrate the 80th birthday of Prof. Dr. Erik De Clercq on 28 March 2021, this review provides an overview of his contributions to eight approved nucleos(t)ide drugs: (i) three adenosine nucleotide analogues, namely tenofovir disoproxil fumarate (Viread) and tenofovir alafenamide (Vemlidy) against HIV and HBV infections and adefovir dipivoxil (Hepsera) against HBV infections; (ii) two thymidine nucleoside analogues, namely brivudine (Zostex) against HSV-1 and VZV infections and stavudine (Zerit) against HIV infections; (iii) two guanosine analogues, namely valacyclovir (Valtrex, Zelitrex) against HSV and VZV and rabacfosadine (Tanovea-CA1) for the treatment of lymphoma in dogs; and (iv) one cytidine nucleotide analogue, namely cidofovir (Vistide) for the treatment of HCMV retinitis in AIDS patients. Although adefovir dipivoxil, stavudine, and cidofovir are virtually discontinued for clinical use, tenofovir disoproxil fumarate and tenofovir alafenamide remain the most important antivirals against HIV and HBV infections worldwide. Overall, the broad-spectrum antiviral potential of nucleos(t)ide analogues supports their development to treat or prevent current and emerging infectious diseases worldwide.
Topics: Anniversaries and Special Events; Antiviral Agents; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Nucleosides; Nucleotides; Virus Diseases; Viruses
PubMed: 33572409
DOI: 10.3390/molecules26040923 -
HIV Medicine May 2021Hypertension is a growing health concern in people living with HIV (PLWH). However, association between HIV infection and hypertension is equivocal.
OBJECTIVES
Hypertension is a growing health concern in people living with HIV (PLWH). However, association between HIV infection and hypertension is equivocal.
METHODS
In all, 1472 PLWH and 2944 HIV-negative individuals frequency-matched by age and sex were derived from the baseline survey of Comparative HIV and Aging Research in Taizhou (CHART), China. Prehypertension was defined as systolic blood pressure (BP) of 120-139 mmHg and/or diastolic blood pressure of 80-89 mmHg.
RESULTS
Despite the fact that prevalence of hypertension was overall lower among PLWH than among HIV-negative people (21.1% vs. 29.1%, P < 0.001), it was similar at ages 18-29 (7.6% vs. 8.5%) and 30-44 years (17.1% vs. 18.5%) but significantly lower in PLWH at ages 45-59 (26.1% vs. 40.7%) and 60-75 years (37.1% vs. 57.3%). Prehypertension prevalence was consistently higher in PLWH across all age groups. In the model adjusting for traditional risk factors, HIV infection was associated with hypertension (adjusted odds ratio [aOR] = 1.27, 95% confidence interval: 1.04-1.55) and prehypertension (aOR = 1.77, 95% CI: 1.51-2.08), and attenuated after additional adjustment for abdominal obesity. Age-stratified analysis showed that these associations of HIV with hypertension were observed at ages 18-29 and 30-44 years and associations with prehypertension were observed at ages 18-29, 30-44 and 45-59 years only. Years since HIV diagnosis and stavudine use were the HIV-specific factors independently associated with hypertension or/and prehypertension.
CONCLUSIONS
HIV infection is independently associated with prehypertension and hypertension especially at younger ages, and this risk may increase as treatment becomes prolonged. Our findings reinforce the urgent necessity for active BP screening and control strategies be adopted for PLWH in China.
Topics: Adolescent; Adult; Blood Pressure; China; HIV Infections; Humans; Hypertension; Middle Aged; Prehypertension; Prevalence; Risk Factors; Young Adult
PubMed: 33421323
DOI: 10.1111/hiv.13040 -
PloS One 2020Combination antiretroviral drugs (cARVs) prolong patients' lives but are unfortunately thought to increase complications related to metabolic disorders including type-2... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
Combination antiretroviral drugs (cARVs) prolong patients' lives but are unfortunately thought to increase complications related to metabolic disorders including type-2 Diabetes Mellitus (DM). We sought to confirm the association of cARVs with type-2 DM and ascertain the extent of this association in a rural South African setting.
METHODS
A case-control study of 177 (33.33%) cases with HIV/AIDS and type-2 DM were selected and compared with 354 (66.67%) non-DM HIV/AIDS unmatched controls from a rural district of South Africa's third most populous province (Eastern Cape). Cases were identified from community health centres using the district health information system, and controls were identified using simple random sampling from the same health facilities. Odds Ratios (OR), together with 95% confidence intervals, were calculated for all the univariable and multivariable logistic analyses.
RESULTS
This study found that cARVs significantly increased the occurrence of type-2 DM among HIV patients. Patients on protease inhibitors (PIs) were at least 21 times significantly (p<0.0001) more likely to be diabetic than those on the fixed dose combination (FDC); those on stavudine (D4T) and zidovudine (AZT) were 2.45 times and 9.44 times respectively more likely to be diabetic than those on FDC (p<0.05). The odds of diabetes increased by more than three-folds for those who had been on antiretroviral drugs for more than 6 years (p<0.005).
CONCLUSION
This study has been able to establish the association between cARVs and type-2 DM. It therefore proposes consideration of the usage of AZT, D4T, lopivavir and ritonavir for the treatment of HIV. The study further proposes more prospective research to test these findings further.
Topics: Adult; Diabetes Mellitus, Type 2; Female; HIV Infections; Humans; Male; Middle Aged; Prospective Studies; Rural Population; South Africa; Stavudine; Time Factors; Zidovudine
PubMed: 33382732
DOI: 10.1371/journal.pone.0244067 -
Bioscience Trends Jan 2021Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries... (Observational Study)
Observational Study
Metabolic syndrome (MS) is common among obese people. Little is known about the magnitude and characteristics of MS in people living with HIV (PLWH) in Asian countries in general and China in particular. Using baseline data collected between February 2017 through January 2020 from the Comparative HIV and Aging Research in Taizhou (CHART) cohort in China, we examined MS among 2,227 PLWH and 5,264 matched people without HIV, respectively. MS was defined using the criteria set forth by the International Diabetes Federation (IDF). Approximately 76.7% of PLWH had body mass index (BMI) < 24.0 kg/m, significantly higher than people without HIV (50.3%). Among participants with BMI < 24.0 kg/m, PLWH had a significantly higher prevalence of MS than people without HIV (20.6% vs. 14.5%; aOR: 1.41, 95% CI: 1.19-1.68) overall, and at an age of 18-29 (10.4% vs. 3.4%, aOR: 3.49, 95% CI: 1.99-6.11) and 30-44 years (17.3% vs. 8.5%, aOR: 2.03, 95% CI: 1.47-2.81), respectively. Among participants with BMI ≥ 24.0 kg/m, MS prevalence was not significantly different between PLWH and people without HIV overall, but significantly lower in PLWH than people without HIV for those aged over 60 years (65.9% vs. 77.8%, aOR: 0.53, 95% CI: 0.32-0.88). Among PLWH, MS was significantly associated with older age and higher CD4 cell count, and with stavudine (d4T) use only in the group of BMI < 24.0 kg/m. Our finding is indicative of a relatively higher risk for early onset of MS among HIV-infected young adults with lower BMI. Research is needed to elucidate the pathogenic mechanism for MS among PLWH.
Topics: Adolescent; Adult; Age Factors; Age of Onset; Aged; Anti-HIV Agents; Body Mass Index; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; China; Cohort Studies; Cross-Sectional Studies; Female; HIV Infections; Humans; Male; Metabolic Syndrome; Middle Aged; Prevalence; Risk Factors; Stavudine; Young Adult
PubMed: 33328394
DOI: 10.5582/bst.2020.03351 -
European Journal of Pharmacology Jan 2021COVID-19 has intensified into a global pandemic with over a million deaths worldwide. Experimental research analyses have been implemented and executed with the sole...
COVID-19 has intensified into a global pandemic with over a million deaths worldwide. Experimental research analyses have been implemented and executed with the sole rationale to counteract SARS-CoV-2, which has initiated potent therapeutic strategy development in coherence with computational biology validation focusing on the characterized viral drug targets signified by proteomic and genomic data. Spike glycoprotein is one of such potential drug target that promotes viral attachment to the host cellular membrane by binding to its receptor ACE-2 via its Receptor-Binding Domain (RBD). Multiple Sequence alignment and relative phylogenetic analysis revealed significant sequential disparities of SARS-CoV-2 as compared to previously encountered SARS-CoV and MERS-CoV strains. We implemented a drug re-purposing approach wherein the inhibitory efficacy of a cluster of thirty known drug candidates comprising of antivirals, antibiotics and phytochemicals (selection contingent on their present developmental status in underway clinical trials) was elucidated by subjecting them to molecular docking analyses against the spike protein RBD model (developed using homology modelling and validated using SAVES server 5.0) and the composite trimeric structures of spike glycoprotein of SARS-CoV-2. Our results indicated that Camostat, Favipiravir, Tenofovir, Raltegravir and Stavudine showed significant interactions with spike RBD of SARS-CoV-2. Proficient bioavailability coupled with no predicted in silico toxicity rendered them as prospective alternatives for designing and development of novel combinatorial therapy formulations for improving existing treatment regimes to combat COVID-19.
Topics: Amides; Anti-Bacterial Agents; Antiviral Agents; Binding Sites; Drug Repositioning; Esters; Gabexate; Guanidines; Molecular Docking Simulation; Phytochemicals; Protein Binding; Pyrazines; Raltegravir Potassium; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Stavudine; Tenofovir; COVID-19 Drug Treatment
PubMed: 33160938
DOI: 10.1016/j.ejphar.2020.173720