The emergence of drug resistant HIV variants and novel anti-retroviral therapy

After its identification in 1980s,HIV has infected more than 30 million people worldwide.Inthe era of highly active anti-retroviral therapy,anti-retroviral drug resistance results frominsufficient anti-retroviral pressure,which may lead to treatment failure.Preliminary studiessupport the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developedworld;however,a highly heterogeneous horde of viral quasi-species are currently circulating indeveloping nations.Thus,the prioritizing of strategies adopted in such two worlds should be quitedifferent considering the varying anti-retroviral drug resistance prevalence.In this article,weexplore differences in anti-retroviral drug resistance patterns between developed and developingcountries,as they represent two distinct ecological niches of HIV from an evolutionary standpoint.

Prevalence survey of infection with Treponema pallidum among HIV-positive patients in Tehran

Objective:To identify the frequency of syphilis among Iranian HIV-positive patients.Methods:A cross-sectional study on the prevalence of syphilis and HIV co-infection among 450 patients diagnosed with HIV infection was conducted between 2004 and 2008 at Imam Khomeini hospital,Tehran,Iran.The lab tests including CD4 cell count,cerebrospinal fluid,veneral disease research laboratory(VDRL),fluorescent treponema antibody-absorption(FTA-Abs)and viral load were performed for all the patients.Data regarding medical history and their demographics were also collected.Results:Of all 450 HIV-positive patients,24(5.3%)had a positive VDRL test and only two men had a FTA-Abs positive test which means 0.45%of them had a definite co-infection of syphilis.65.3%of the HIV-positive patients were injection drug users that the co-infection prevalence of them was 0.7%.We did not find any patient with neurosyphilis.Conclusions:Considering the increasing prevalence of HIV and also extensive use of highly active antiretroviral therapy in developing nations,the diagnosis of syphilis should be timely established using screening tests among such patients.

Phylogeny and drug resistance of HIV PR gene among HIV patients receiving RT inhibitors in Iran

Objective: To survey the level and patterns of reverse transcriptase-based drug resistance and subtype distribution among antiretroviral-treated HIV-infected patients receiving only reverse transcriptase inhibitors in Iran.Methods: A total of 25 samples of antiretroviral therapy experienced patients with no history of using protease inhibitors were collected. After RNA extraction, reverse transcriptase-nested PCR was performed. The final products were sequenced and then analysed for drug-resistant mutations and subtypes.Results: No drug resistant mutations were observed among the 25 subjects. The results showed the following subtypes among patients: CRF 35_AD(88%), CRF 28_BF(8%),and CRF 29_BF(4%).Conclusions: A significant increase in drug resistance has been noted in recentlyinfected patients worldwide. Subtype distributions are needed to perform properlydesigned surveillance studies to continuously monitor rates and patterns of transmitted drug resistance and subtypes to help guide therapeutic approaches and limit transmission of these variants.

Prevalence of HIV infection and the correlates among homeless in Tehran,Iran

Objective:To determine the prevalence of HIV infection among homeless men and women and the related risk behaviors in Tehran,Iran.Methods:In 2007-2008,Tehran municipality stacked up 10657 homeless men and women for assessment of HIV and began collaboration with Iranian Research Center for HIV/AIDS(IRCHA)departments to conduct HIV infection prevalence surveys in homeless populations.The results were analyzed for associations with demographic information,family support,status of drug abuse and relation with family and friends.Results:Overall HIV prevalence was 1.7%(95%confidence interval 1.4-1.9).Factors independently associated with HIV infection included history of using drugs[AOR 8.15(4.86-13.67)].older age[AOR1.80(1.08-2.99)for 40-55 yr],occupation[AOR 1.64(1.19-2.24)for unemployed],and no relation with family[AOR 1.82(l.30-2.54)|.Conclusions:This study supports the idea that injection drug use is contributing to the increased spread of HIV among Iranian homeless.Harm reduction programs should be expanded,particularly among homeless injection drug users.

Validity and Reliability of an Information-Motivation-Skill-Behavior Questionnaire: A Gender-Sensitive HIV Survey

Background: Despite the essence of HIV-related surveys, their precision in measurement of intended constructs has been an area of controversy. Considering the increasing trend of sexual transmission of HIV among women, standard gender-sensitive tools can yield pivotal information for researchers and policy-makers in Iran. Aim: To evaluate the reliability and validity of a questionnaire (IMSB) based on the Information-Motivation-Behavior model of HIV-related behavior prediction. Methods: The IMSB survey constituted of five main domains: HIV-related knowledge, attitudes toward people living with HIV, motivation to practice safe-sex, skills to practice safe-sex, and HIV-related behaviors. Completed questionnaires (n = 189) from pilot phases of three projects were accessed. We assessed face and content validity through expert consultation and respondent feed-backs for the primary pool of items. Discriminant validity was measured utilizing non-parametric tests. Cronbach’s alpha was calculated for each domain to assess internal consistency, and paired t-tests were used to measure stability over time. Results: The primary pool of items was reduced in the process of validation. The discriminant validity was appraised to be favorable since the survey can differentiate between age groups, women with different levels of education and marital status. The survey was reliable in 4 domains;but a Cronbach’s alpha of 0.6 was reported for the fifth domain (HIV-related behaviors). Younger women had higher knowledge and motivation scores;single women were more motivated to practice safe-sex and divorced/widowed women had lower motivation and skills scores. Conclusion: This questionnaire can be used as a valid and reliable tool to measure the IMB constructs. The lower reliability of the “behavior” domain is probably rooted in societal norms and cultural definitions. The integration of motivation and skill domains can provide valuable information for clinicians/interventionists to address vulnerabilities experienced by their female clients.

Effectiveness of online HIV treatment services in the context of the COVID‐19 pandemic

Background:The COVID‐19 pandemic has created challenges with respect to HIV care services.Remote online services might provide an effective method for health service delivery to people living with HIV(PLHIV).Few studies have focused on the efficacy of telemedical services for PLHIV and the effect of antiretroviral treatment via online services in China.Methods:We developed a platform called the“No.8 Health”for online antiretroviral drug collection and delivery services in Beijing from January 21 to June 30,2022.We evaluated the online treatment service according to viral load suppression rates and compared differences in social characteristics between PLHIV who received antiretroviral drugs through online or offline treatment services.Results:By June 2022,9528 PLHIV had received outpatient treatment services,among which 44.6%(4031/9528)used the online treatment and drug delivery services for a total of 5590 person‐times.The satisfaction rate was 100%.Rates of viral load suppression among PLHIV who initiated antiretroviral therapy(ART)in 2020 and 2021 were 96.4%and 93.1%,respectively.Results showed that the viral load suppression rate was 97.9%.Regarding HIV rapid self‐testing,4513 men who have sex with men used the online HIV rapid testing service.The number of users was approximately the same as in 2021,but both were slightly lower than those in 2020.Conclusion:This study was the first to evaluate the effect of online drug collection and delivery services and virologic outcomes among PLHIV in China.The online service helped with maintenance of ART services,but the COVID‐19 pandemic still had some impacts on viral load suppression.

Ebola viral disease: a review literature

Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately95% of the patients appear signs within 21 d after exposure. Typical features include fever,profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred.Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer(four-fold) contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a "cocktail"of humanized-mouse antibodies(ZMapp), recombinant inhibitor of factor VIIa/tissue factor,activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.

Reinfection risk of novel coronavirus(COVID-19):A systematic review of current evidence

BACKGROUND There is recently a concern regarding the reinfection and reactivation of previously reCoVered coronavirus disease 2019(CoVID-19)patients.AIM To summarize the recent findings and reports of CoVID-19 reinfection in patients previously reCoVered from the disease.METHODS This study was a systematic review of current evidence conducted in August 2020.The authors studied the probable reinfection risk of novel coronavirus(CoVID-19).We performed a systematic search using the keywords in online databases.The investigation adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)checklist to ensure the reliability and validity of this study and results.RESULTS We reviewed 31 studies.Eight studies described reCoVered patients with reinfection.Only one study reported reinfected patients who died.In 26 studies,there was no information about the status of the patients.Several studies indicated that reinfection is not probable and that post-infection immunity is at least temporary and short.CONCLUSION Based on our review,we concluded that a positive polymerase chain reaction retest could be due to several reasons and should not always be considered as reinfection or reactivation of the disease.Most relevant studies in positive retest patients have shown relative and probably temporary immunity after the reCoVery of the disease.

Zika virus:A review of literature

Zika virus(ZIKV) has two lineages:African and Asian.Mosquito-borne flaviviruses are thought to replicate initially in dendritic cells and then spread to lymph nodes and the blood stream.Risk for infection through blood transfusion,sexual practices and perinatal transmission exists.The possible routes of perinatal transmission are during delivery,breastfeeding and by close contact between the mother and her newborn.Also,mucocutaneous exposures to the virus by infected blood or monkey bite,organ transplantation or hemodialysis are the other routes of ZIKV transmission.There are two types of ZIKV infection;Zika fever and congenital infection.Clinical presentation of Zika fever varies from asymptomatic infections to a self-limiting febrile disease with low grade fever,conjunctivitis,maculopapular rash,headache,retro-orbital pain and arthritis/arthralgia with periarticular edema,myalgia,vertigo,vomiting and asthenia.This clinical feature could be mistaken for dengue or chikungunya fevers.Microcephaly is the most important and frequently reported clinical picture of suspected congenital Zika syndrome.Laboratory tests are needed for diagnosis of ZIKV infection,because there is no known pathognomonic clinical,biochemical or radiological features.RT-PCR is the most wellliked assay.Serum samples are tested by immunoglobulin G ELISA with ZIKV antigen.Samples are also tested by immunoglobulin M ELISA.There is no certified vaccine or therapeutic medication.In asymptomatic or uncomplicated patients,treatment is not necessary.

The Association of Hepatitis B Vaccine Supply Policy with Timing of Receipt of the First Dose of Hepatitis B Vaccination

An estimated 800,000 - 1.4 million persons in the US have chronic hepatitis B virus (HBV) infection. The risk for chronic infection is greatest among young children;approximately 90% of infants will remain chronically infected with HBV. Approximately 25% of those who become chronically infected during childhood die prematurely from cirrhosis or liver cancer. Hepatitis B vaccination is the most effective measure to prevent HBV infection and its consequences. In 2006, 29 US states had Hepatitis B Vaccine Supply (HBVS) policy which either supplies hepatitis B vaccine at no cost to all providers for all children or provides hepatitis B vaccine to delivery hospitals-only free of charge for all infants;other 21 US states and the District of Columbia did not have. 17,636 infants born in 2006 obtained from 2007-2009 National Immunization Survey (NIS) were analyzed with survival analysis procedures of Kaplan-Meier estimate and Cox proportional hazards model for complex sample survey to evaluate the association between state HBVS policy and the timing of infant age in days to receipt of hepatitis B vaccination. State HBVS policy is associated with infant age in days from birth to receipt of the first dose of hepatitis B vaccine (P < 0.01), and to completion of the 3-dose hepatitis B vaccine series (P < 0.01). Receipt of the first dose of hepatitis B vaccine occurred 31% earlier among infants residing in states with HBVS policy than among infants residing in states without (adjusted hazards ratio 1.31, 95%CI (1.23, 1.39)). Completion of the 3-dose hepatitis B vaccine series were 12% sooner among infants living in states with HBVS policy than among infants living in states without (adjusted hazards ratio 1.12, 95%CI (1.06, 1.18)). State HBVS policy may help overcome barriers to timely delivery of hepatitis B vaccines to infants.

Early initiation of antiretroviral treatment: Challenges in the Middle East and North Africa

New World Health Organization guidelines recommend the initiation of antiretroviral treatment(ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm3. Substantial reduction of human immunodeficiency virus(HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa(MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it's at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients' CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners- either female sex workers or women in monogamous relationships with high-risk men- are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by costeffective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region.

Impact of Age on CD4 Response to Combination Antiretroviral Therapy: A Study in Tehran, Iran

Background: This study was undertaken to address the controversy regarding immunologic response to combination antiretroviral therapy (cART) among older patients. Methods: In a cross-sectional study all patients attending the HIV Clinic at Imam Khomeini Hospital (Tehran) from 2010 to 2011 were evaluated. Immunologic response was investigated using consecutive CD4+ T-cell counts in a one-year interval and outcomes were analyzed for older (>=50 yrs) and younger (<50 yrs) patients using SPSS version 16.0. Results: A total of 714 patients were actively enrolled in the clinic while 24 were 50 years or older, and had initiated ART;a similar random group of younger patients was selected as the control. Hepatitis C was the most prevalent co-infection in both groups. Patients with no serologic evidence of hepatitis B and C had significantly higher CD4+ T-cell counts than HIV/HBV co-infected patients after 12 months (p = 0.04). The average increased CD4+ T-cell counts in 6, 9, and 12 months of cART initiation were lower among older patients but the difference was not significant (50.75 vs. 123.08;p = 0.37, 132.87 vs. 710.58;p = 0.25, 271.27 vs. 500;p = 0.65). Conclusion: About 11% of the registered HIV-positive patients at our clinic were 50 years or older while their immunologic response to cART showed to be different. Specific needs of older HIV infected patients are highly recommended to be addressed in future treatment and care programs.

Immunity:研究开发出最优的HIV疫苗递送模式

HIV已不再占据头条新闻。这主要是因为抗逆转录病毒药物的成功开发已将HIV病毒感染导致的艾滋病（AIDS）转化为一种慢性的可控制的疾病。然而。当前在全世界大约0．367亿名HIV感染者中，仅约一半的人能够获得控制这种病毒所需的药物。与此同时。新的HIV感染率持续保持在非常高的水平，这突出强调了需要开发一种预防性疫苗。然而，几十年来。

Effect of green tea consumption in treatment of mild to moderate depression in Iranian patients living with HIV: A double-blind randomized clinical trial

Objective: Depression affects people living with HIV(PLWH) compliance leading to poor control infection.Previous observational studies showed an anti-depression effect of green tea extract(GTE). The therapeutic effect of GTE on depression were investigated in PLWH receiving antiretroviral therapy(ART).Methods: Fifty PLWH on ART with diagnose of mild to moderate of depression, participated in a doubleblind, placebo-controlled trial and underwent 12 weeks of treatment with either 400 mg GTE capsules or placebo twice daily. The Hamilton depression scale of patients was measured before, 6 weeks and 12 weeks after treatment in two groups. The primary outcome measure was performed to evaluate the efficacy of GTE in improving depressive symptoms.Results: The mean of Hamilton score showed a significant difference between the two groups after 12 weeks(P = 0.035). Repeated measures ANOVA test showed a significant effect for time ? treatment interaction on the Hamilton mean score between the two groups(P = 0.000).Conclusion: It seems the use of GTE capsules in PLWH on ART is safe and could lead to greater and more rapid improvement in depressive symptoms than placebo. Thus it can be considered as an alternative therapy for mild to moderate depression. Further studies with higher sample size and longer followup and comparisons with other antidepressive drugs are warranted.

Development of a Multiplex Real-Time Quantitative PCR Assay for Detecting Vaginal Microbiota in Chinese Women-China,2021-2022

Introduction:The Nugent score,limited by subjectivity and personnel requirements,lacks accuracy.Establishing a precise and simple molecular test is therefore essential for detecting vaginal microbiota compositions and evaluating vaginal health.Methods:We evaluated the vaginal health of Chinese women using quantitative polymerase chain reaction(qPCR)to target Lactobacillus crispatus(L.crispatus),L.iners,Gardnerella vaginalis(G.vaginalis),Atopobium vaginae(A.vaginae),and Megasphaera phylotype1.bacterial vaginosis(BV)-related bacteria shared a fluorescent channel.Using 16S rDNA sequencing as a reference standard,we evaluated and validated the diagnostic accuracy of the qPCR assay.Results:Both qPCR and 16S rDNA sequencing demonstrated 90.5%concordance in segregating vaginal community state type(CST),as visualized through heatmaps and PCoA.Spearman’s correlation analysis revealed strong correlations between the two methods in calculating the RA of L.crispatus(CST I),L.iners(CST III),and BV-related bacteria(CST IV),with coefficients of 0.865,0.837,and 0.827,respectively.Receiver operating characteristic analysis showed that qPCR had significant diagnostic accuracy for CST I,CST III,and CST IV(molecular BV),with area under the curve values of 0.967,0.815,and 0.950,respectively,indicating strong predictive power.Discussions:Vaginal health can be evaluated using a single qPCR amplification experiment,making the multiplex qPCR assay a highly accurate tool for this purpose.

2013-2015年美国结核病发病率水平调查分析

在消除结核病(tuberculosis,TB)的进程中,美国实现持续20年结核病发病率每年减少超过0.2/10万,2013—2015年美国的结核病发病率保持在3.0/10万左右。美国国家结核病监测系统(National Tuberculosis Surveillance System)获得的初步数据显示,非美国出生人口结核病发病率(15.1/10万)大约为美国出生人口发病率(1.2/10万)的13倍。在美国继续降低结核病发病率以至最终消除结核病,需要美国和全球共同加强努力,包括在美国加强对结核病潜伏感染者的检测和治疗,在全球和美国加强措施阻断结核病传播,加快全球结核病的下降速度,尤其是要降低美国结核病患者原籍地国家的结核病发病率。

2007-2013年美国高中生睡眠时间与伤害相关的危险行为调查报告

高中生普遍睡眠时间不足，这与机动车事故、运动损伤以及职业伤害的危险增加有关。为了评估学生自我报告的上学期间晚间平均睡眠时间与几种伤害相关的危险行为（包括极少戴自行车头盔、极少系安全带、乘坐酒驾司机的车、酒后驾驶、驾驶时发短信）间的关联，美国疾病预防控制中心（CDC）分析了2007年、2009年、2011年和2013年参与全国青少年危险行为调查（youthriskbehaviorsurveys，YRBSs）的50370名高中生（9～12年级）的数据。

Modeling the impact of changing sexual behaviors with opposite-sex partners and STI testing among women and men ages 15-44 on STI diagnosis rates in the United States 2012-2019

Objective:To estimate the potential contributions of reported changes in frequency of penile-vaginal sex(PVS),condom use and STI screening to changes in gonorrhea and chlamydial diagnoses from 2012 to 2019.Methods:An agent-based model of the heterosexual population in the U.S.simulated the STI epidemics.Baseline was calibrated to 2012 diagnosis rates,testing,condom use,and frequency of PVS.Counterfactuals used behaviors from the 2017-2019 NSFG,and we evaluated changes in diagnosis and incidence rates in 2019.Results:Higher testing rates increased gonorrhea and chlamydia diagnosis by 14%and 13%,respectively,but did not reduce incidence.Declining frequency of PVS reduced the diagnosis rate for gonorrhea and chlamydia 6%and 3%respectively while reducing incidence by 10%and 9%respectively.Declining condom use had negligible impact on diagnosis and incidence.Conclusion:Understanding how changing behavior drives STI incidence is essential to addressing the growing epidemics.Changes in testing and frequency of PVS likely contributed to some,but not all,of the changes in diagnoses.More research is needed to understand the context within which changing sexual behavior and testing are occurring.

The antimicrobial susceptibility profile of ESKAPE pathogens from urinary tract infections in a referral laboratory,Northeast Iran

Objective:To assess the antimicrobial susceptibility pattern of ESKAPE pathogens from Neyshabur,Iran during 2013-2015.Methods:A total of 345 isolates including 62 Staphylococcus aureus(S.aureus),38 Enterobacter spp.(including 14 Enterobacter agglomerans,6 Enterobacter aerogenes and other 18 Enterobacter spp.),123 Enterococcus faecium,78 Klebsiella pneumonia,10 Pseudomonas aeruginosa and 34 Acinetobacter baumannii were isolated.The antimicrobial susceptibility pattern of isolates was conducted with Kirby Bauer method.Data were analyzed with SPSS 20.0 software using F-and t-tests.Results:Among S.aureus isolates,the highest resistance was observed against nalidixic acid(81.35%)and cefixime(74.50%).Thirty-three(53.22%)S.aureus isolates were cefoxitin resistant(methicillin-resistant S.aureus).The majority of Enterobacter species was resistant to amikacin(100.00%)and cephalotin(66.60%).Most Enterococcus faecium isolates were resistant to nalidixic acid(89.43%)and amikacin(83.33%),but vancomycin-resistant enterococci isolates were not detected.Moreover,among Klebsiella pneumonia,the highest resistance was observed to nalidixic acid(20.98%)and cotrimoxazole(28.39%).Furthermore,all Pseudomonas aeruginosa isolates were resistant to cefotaxime(100.00%)and majority to nitroforantoin(88.80%).Acinetobacter baumannii isolates showed the highest and the lowest resistance to cefotaxime(100.00%)and cefixime(88.71%),respectively.Conclusions:The prevalence of ESKAPE pathogens from northeast region was low,but majority of them exhibited high rate of antibiotic resistance to common used antimicrobial agents.

The sero-epidemiology of infectious mononucleosis in Neyshabur,Northeast Iran during 2010-2014

Objective:To detect infectious mononucleosis(IM)prevalence in Neyshabur,Northeast Iran during 2010-2014.Methods:This cross-sectional descriptive epidemiological survey was performed to reveal the prevalence of IM in Neyshabur between 2010 and 2014.A total of 114 individuals were studied.Briefly,individuals with positive test for specific immunoglobulin G and immunoglobulin M in the agglutination test were determined as positive cases.Results:The overall prevalence of IM was 14%.Mean±SD of age for IM test was 18.96±15.79.The age groups of 0-10 and 21-30 were the most positive cases in this period.In addition,31-40 and over 50 years were not positive cases.Male individuals were significantly more positive and likewise,it was observed that there were significantly higher positive cases of IM in spring and summer.Conclusions:Among the five years of this study,it was a decreasing status from 2010(23.1%)to 2014(9.1%),though a slight fluctuation had occurred.The prevalence of IM was low in Neyshabur City.Moreover,children and male individuals had relatively higher prevalence of the disease.Furthermore,it was observed a higher rate of IM in spring and summer.