How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

HIV/AIDS患者合并宫颈癌与癌前病变的影响因素分析

目的探讨艾滋病病毒(HIV)感染者和艾滋病(AIDS)患者合并宫颈癌与癌前病变的相关影响因素。方法以在本院诊治的40例HIV/AIDS(HIV抗体阳性)合并宫颈癌与癌前病变患者为观察组,等距抽样选择同期在本院诊治的40例HIV抗体阴性宫颈癌与癌前病变患者为对照组,对其相关危险行为、宫颈癌与癌前病变的程度进行横断面调查。结果观察组中HIV感染者19例(47.50%),AIDS患者21例(52.50%);两组多性伴、性病史、配偶/固定性伴有多性伴、配偶/固定性伴HIV抗体阳性差异具有高度统计学意义(45.00%比10.00%、37.50%比7.50%、82.50%比27.50%、72.50%比2.50%,P均<0.01);两组宫颈病变不同程度中CINⅢ与宫颈癌的发生率差异具有高度统计学意义(57.50%比15.00%与27.50%比2.5%,P均<0.01),CINⅡ的发生率与孕次≥3次比较差异无统计学意义(15.00%比32.50%,65.00%比50.00%)。结论 HIV/AIDS患者合并宫颈癌与癌前病变的影响因素与多性伴、性病史、配偶/固定性伴有多性伴、配偶/固定性伴HIV抗体阳性密切相关;HIV抗体阳性者CINⅢ与宫颈癌的发生率显著高于HIV抗体阴性者。

HIV感染导致MT4细胞蛋白表达差异的初步研究

为了比较MT4细胞株感染HIV-1的ⅢB株前后的蛋白质表达差异,我们分别提取MT4细胞及感染了人类免疫缺陷病毒(HIV)的MT4细胞的总蛋白质,通过双向电泳分离,使用ImageMaster2DElite3.10图像分析软件分析获得的凝胶图谱,寻找差异点,使用质谱仪鉴定获得的差异点蛋白质。结果表明感染HIV和未感染HIV的MT4细胞有40个蛋白质点差异,HIV感染后减少的蛋白质点有12个,增多的有28个,通过质谱分析,29个蛋白质得到鉴定。其中HIV感染后下调的蛋白质有能量代谢相关蛋白、肌动蛋白相关蛋白及假想蛋白等;上调的蛋白有肌动蛋白、酶类蛋白、免疫蛋白及假想蛋白等。通过研究我们可以看出宿主细胞感染HIV病毒后有多个蛋白发生变化,可能和HIV与宿主细胞的相互作用有关。为了研究HIV感染的机制必须去除高丰度蛋白,针对特定功能的蛋白质进行具体研究。

Smartphone-Imaged HIV-1 Reverse-Transcription Loop-Mediated Isothermal Ampliflcation(RT-LAMP) on a Chip from Whole Blood

Viral load measurements are an essential tool for the long-term clinical care of human immunodeficiency virus （HIV）-positive individuals. The gold standards in viral load instrumentation, however, are still too limited by their size, cost, and sophisticated operation for these measurements to be ubiquitous in remote settings with poor healthcare infrastructure, including parts of the world that are disproportionately affected by HIV infection. The challenge of developing a point-of-care platform capable of making viral load more accessible has been frequently approached but no solution has yet emerged that meets the practical requirements of low cost, portability, and ease-of-use. In this paper, we perform reverse-transcription loop-mediated isothermal amplification （RT-LAMP） on minimally processed HIV-spiked whole blood samples with a microfluidic and silicon microchip platform, and perform fluorescence measurements with a consumer smartphone. Our integrated assay shows amplification from as few as three viruses in a - 60 nL RT- LAMP droplet, corresponding to a whole blood concentration of 670 viruses per μL of whole blood. The technology contains greater power in a digital RT-LAMP approach that could be scaled up for the determination of viral load from a finger prick of blood in the clinical care of HIV-positive individuals. We demonstrate that all aspects of this viral load approach, from a drop of blood to imaging the RT-LAMP reaction, are compatible with lab-on-a-chip components and mobile instrumentation.

Development and Challenge of HIV/AIDS Testing Laboratory Network and Quality Assurance System in China

This paper describes the development and challenge of HIV/AIDS testing laboratory network and quality assurance system in China. At present,the HIV/AIDS testing laboratories includes three classes,the National AIDS Reference Laboratory,HIV/AIDS confirmatory laboratories and HIV/AIDS screening laboratories. All of them are accredited by the health authorities,and each class of laboratories take charge of their function strictly according to the "National Management of HIV/AIDS Detection (2006)". A complete quality assurance and quality control system for HIV/AIDS testing has been developed,which includes technical training,strict laboratory monitoring and approval,examination or proficiency testing on HIV/AIDS detection,and quality evaluation and supervision of HIV/AIDS diagnostic kits. Besides conduct the routine anti-HIV antibody test,more and more laboratories began to conduct other tests,such as CD4+ T lymphocyte cell counting,HIV viral load,HIV DNA PCR,genotyping,drug resistance,and HIV-1 recent infection test. The primary challenges faced by the HIV/AIDS testing laboratory network are in the areas of laboratory management and quality control. For example,the provincial PT program is inefficient,the internal quality control is conducted perfunctorily,personnel training can not met the needs of the workplace,which need to be improved.

HIV and HCV:from Co-infection to Epidemiology,Transmission,Pathogenesis,and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.

Analysis of causes for liver function deteriora-tion in patients with HIV/HCV co-infection

BACKGROUND:Co-infection of hepatitis C virus (HCV) and human immunodeficiency virus type 1 ( HIV-1 ) is common in hemophiliacs and drug abusers. To assess the interaction between HIV and HCV disease progression, we examined 82 HIV/HCV co-infection patients and 62 HCV infection patients. METHODS: Liver function, pathological changes, infec- tion duration, immune function and qualitative HCV-RNA and HCV antibody were compared retrospectively between the two groups of patients. RESULTS: Fourty-eight patients (58.5%) in the HIV/ HCV co-infection group and 53 patients (85.5%) in the HCV infection group showed abnormal liver function. No significant difference was observed in inflammation and fi- brosis in the two groups P =0.187, 0.954). However, liver abnormality in the patients with HIV/HCV co-infection appeared 8 years earlier than in those with HCV infection alone (P<0.001). As to immune function, the counts of CD4+T and CD8+ T in the HIV/HCV group were (226.35 ± 173.49)×106/L and (914. 40 ±448. 28)×106/L, whereas in the HCV group they were (752.31±251.69)×l06/L and (529.011170.67)×106/L respectively. The difference in the two groups was highly significant (P<0.001; P<0.001). The ratio of the number of people with both HCV-RNA and HCV antibody positive to the number of HCV-RNA positive and HCV antibody negative in the HIV/HCV group was 52:9, whereas in the HCV group it was 44:1 (P = 0.043). CONCLUSION: HIV/HCV co-infection can accelerate de- terioration of hepatitis C, which may be due to the effect of HIV on cellular immunity and humoral immunity of the body.

“Unconventional”Neutralizing Activity of Antibodies Against HIV

Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by inununization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using ＂conventional＂ neutralization assay which uses phytohemagglutinin （PHA）-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4^＋T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the ＂conventional＂ neutralization assay, do exhibit potent and broad neutralizing activity in ＂unconventional＂ ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and inunature dendritic cells （iDCs）, or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.

The Status of Human Immuno-deficiency Virus （HIV） Infection among Youth Aged 15-24 Years in Malawi and Kenya

HIV （Human Immuno-deficiency Virus） prevalence in Malawi is one of the highest in the world, with 10.3% of population living with HIV. Kenya has a prevalence rate of 6% and with 1.6 million people living with HIV infection. The broad objective of the study was to assess the proportion of youth aged 15-24 years affected by HIV in Malawi and Kenya. This was a descriptive study design. Data were mainly collected from reports from government, World Bank, World Health Organization and UN agencies. Graphs, tables and charts have been used to present statistics. Data for specific age cohort were hard to find and hence, data were used for general HIV and AIDS with special attention to the youth where possible. In Kenya, HIV prevalence among young women jumps three folds from 2.8% of 15-17 year olds to 8.3% among 23-24 year olds. In Malawi, around 2,100 young people and adolescents are infected with HIV every day. In 2013, four million young people aged 15-24 were living with HIV, with 29% aged under 19 years. This age group includes school going youths, newly employed, economically productive and sexually active group. HIV prevalence in Malawi has been declining over time among persons aged 15-19 years from 16.4% in 1999 to 11.8 % in 2004 to 10.6% in 2010 and 10.3% in 2016. However, in Kenya, the trend of HIV prevalence reached its peak of 10.55% in 1995-1996 after which it declined to 6.7% in 2003 and has been stable since then.

Mother-to-Child Transmission of HIV/AIDS during Pregnancy and Delivery and Associated Factors in the Region of Couffo in Benin

Evaluation of the effectiveness of the mother-to-child HIV Prevention Program, in Benin in 2016 reported a national rate of 6.7%. The Region of Couffo, within 12 Regions (departments) in the country, had the highest rate of transmission, which was 16.1%. The study aimed to determine transmission rate during pregnancy and delivery as well as the factors associated with it. This is a retrospective and analytical study based on a sample of seventy (70) babies born to HIV-infected mothers in 2016 in Couffo. Key findings showed, there is a perinatal transmission of five percent (5%) and the factors associated with this transmission are: delay in carrying out first antenatal visits at the health facility, low frequency of visits performed versus number requested and appropriate time, poor health condition of mothers during pregnancy, absence or late start of antiretroviral care and treatment during pregnancy, irregular intake of intermittent presumptive treatment at sulfadoxine-pyrimethamine to prevent malaria, a short antiretroviral therapy (less than three months) for mothers before delivery and the default in cleaning mother’s genital tract with betadine after the woman’s water broke.

HIV在人体免疫网络中传播的动力学研究

虽然抗逆转录病毒疗法(antiretroviral therapy,ART)能够有效地抑制人类免疫缺陷病毒(human immunodeficiency virus,HIV)的复制,但病毒血症现象依然存在.基于此,主要探讨病毒避难所是否存在.研究发现:由于存在血脑屏障,在接受治疗的状况下,大脑中的病毒载量仍然保持在较高稳态,表明大脑确是HIV病毒的避难所;外周血中的病毒水平并不能正确反映身体内其他组织中的病毒载量状况.

A Baseline Studies on the Nutritional Interplay between HIV Drugs and Kidney, Liver and Heart Indices in Patients Receiving HIV Treatment in North-East Nigeria

Human Immunodeficiency Virus (HIV) patients on Antiretroviral Therapy (ART) have shown impressive improvement and death rates have drastically reduced, even though complications still exist. This research carried out a baseline study to determine the nutritional interplay between HIV-drugs and kidney, liver, and heart indices among subjects undergoing HIV treatment and attending the Medical Out-Patient Department of a Federal Medical Center in the North-Eastern part of Nigeria, using a sample size of 50 individuals both male and female, who have been shown to be HIV positive and have been on ART for over 12 months. Anthropometric data was collected in triplicate, two from patients’ file, and one was measured directly and the average was obtained. The electrolytes were determined by the colorimetric method while total protein and albumin in blood concentration were determined by spectrophotometric method, but globulin and A/G ratio were determined by calculation. TC was determined using Spectrophotometric method while HDL was determined after precipitation of LDL with phosphotungstate and magnesium were calculated from Friedwaldís formular, and TG was measured using the colorimetric enzymatic method. The results showed that the mean systolic and diastolic blood pressure which were 119.9 mmHg ± 17.5, and 76. 6 mmHg ± 10.1 respectively, were with the range of the reference values. The mean body mass index was 25.1 ± 4.9;also within range of the reference value. Major indices from the liver function test were mean ALT which was 36.5 ± 29.4 with a reference value of 7 - 55 U/L;AST was 40.0 ± 32.3, with a reference value of 8 - 48 U/L. The mean value for albumin was 4.6 ± 7.1 with a reference range of 3.5 - 5.0 g/dl, these values also were within the reference range values. The electrolyte test showed all other electrolytes to be within the reference range values except for Zinc which was 19.5 μmol/L, with a normal range of 70 - 100 μmol/L and magnesium which was found to be 0.7 mEq/L, with a normal range of 1.5 - 2.0 mEq/L;Zinc and magnesium play vital roles in over 300 enzymatic reactions, and are known to be important in the immune response. Shortfalls in these minerals could compromise the patients’ recovery process and place them at risk of hearts conditions such as arrhythmia or heart attack among many other conditions. There is a need for an immediate review of these treatments in the direction of Zinc and magnesium, either by supplementation or by diet therapy. HIV patients undergoing ART should be placed under strict Zinc and magnesium-rich diet to avert untimely death among these patients. The controlled study should be done to ascertain the best approach to quell the residue of malnutrition in these patients in order to further improve their nutritional status.

CD4+ T-Cell Count, Serum Zinc, Copper and Selenium Levels in HIV Sero-Positive Subjects on ART and ART Naïve Subjects in Port Harcourt, Nigeria

Background: HIV infection results in depletion of immunocompetent cells such as CD4+ T-cells. Trace elements such as Copper, Zinc and selenium are known to be involved in immune function. In recent times, HIV-positive patients are treated with antiretroviral therapy (ART), with significant progress. This study was aimed at evaluating CD4+ T-cells levels, serum Copper, Zinc and Selenium levels in HIV seropositive subjects on ART and ART naive subjects (HIV positive subjects that have not started ART treatment) in Rivers State, Nigeria. Methods: 150 subjects aged 20 to 79 years were recruited after informed consent. 70 subjects were HIV-positive on ART, 30 subjects were HIV-positive ART naïve subjects, while 50 subjects were apparently healthy subjects. Ten (10) milliliters of blood was collected using a standard venipuncture technique from each subject for the analysis of CD4 T-cells using BD fluorescent activated cell sorter (FACSC count), serum Copper and Zinc were analyzed colorimetrically using semi auto-analyzer WP 21E, while selenium was analyzed using atomic absorption spectrophotometer ELICO, SL173. Data generated were analyzed using Graph-Pad Prism version 8.0.2 and p Result: This study revealed a significant reduction in mean zinc, selenium and CD4+ T-cell level respectively (p = 0.0006;0.0001;0.0001) in HIV-Positive subjects on ART and ART naive. There was also a significant increase in mean serum copper level in the HIV-positive subject as compared to control subjects (p = 0.0001). ART treatment improved the CD4+ T cell count and serum levels of selenium and zinc;however, ART did not correct the imbalance. Furthermore, female subjects on ART have a significantly higher CD4+ T-cell count than the males (p Conclusion: Selenium and Zinc deficiency are associated with HIV disease despite the role of ART hence micronutrient supplementation is advised for HIV-positive subjects on ART.

Testing Point of Care Portable Data Capture in a Hospital HIV Transmission Prevention Programme and Experience from Computerized Patient Management in a Sub-Saharan Clinic Setting

Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantages that computerized systems add to medical practice even in resource constrained sub-Saharan clinic settings. Their continued use of paper based systems presents clinical data management and patient care challenges. A portable point of care data capture electronic system and a computerized clinic patient management system （CCPMS） were implemented to remedy these challenges. PMTCT report compilation was easier with the portable data collection system whose data were found to be more complete and accurate with a 0.83% error rate compared to a 4.1% error rate in the paper registers. A resounding majority of clinicians preferred using the new CCPMS with many of the view that it improved drug inventory and general clinic management with a positive effect on patient care.

Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis

The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control efforts.HIV/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and deaths.Rapid screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse prognoses.To date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of HIV/MTB coinfection.Recently,immunology and molecular detection technology has developed rapidly.New detection technologies,such as interferon-γ release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of HIV/MTB coinfection.In this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.

The differential effects of integrase strand transfer inhibitors and efavirenz on neuropsychiatric conditions and brain imaging in HIV-positive men who have sex with men

Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。

Opportunistic ocular infections in AIDS

As the number of HIV infected patients is multiplying exponentially day by day so are the associated ocular complications.The increasing longevity of individuals with HIV disease has resulted in greater numbers of patients with ocular opportunistic infection.By the means of this article we describe various opportunistic ocular infections in AIDS and their clinical manifestations,discussed under four headings;1) adnexal manifestation; 2) anterior segment manifestation;3 ) posterior segment manifestation;4) neuro ophthalmic manifestation. Herpes zoster ophthalmicus,molluscum contagiosum and Kaposi sarcoma are common adnexal manifestations. Molluscum contagiosum being the commonest.Varicella Zoster Virus(VZV) and herpes simplex virus(HSV) most commonly cause infectious keratitis in HIV-positive patients.As compared to the immunocompetent individuals the frequency of bacterial and fungal keratitis is not more in HIV patients,but it tends to be more severe. Posterior segment structures involved in HIV-positive patients include the retina,choroid,and optic nerve head.The herpesvirus family is implicated most commonly in infections of the retina and choroid in HIV positive patients.CMV is the most common cause of retinitis and the commonest intraocular infection in AIDS. Atypical presentations resistance to conventional treatment and higher rate of recurrence make the diagnosis and therapeutic intervention more difficult and challenging.In addition,in one eye,several infections may occur at the same time,rendering the situation more difficult.

Complete Human Immunodeficiency Virus-1 Specific T Lymphocyte Response to Chinese Human Immunodeficiency Virus-1 B/C Chronic Infectors

Objective To characterize the human immunodeficiency virus （HIV） -specific T lymphocyte responses and identify the immunodominant regions in Chinese HIV-1 recombinant subtype B/C chronic infectors at complete genome level. Methods Twenty-five HIV-I B/C recombinant chronic infectors were screened for their specific T lymphocyte responses to a panel of peptides corresponding to the complete HIV-1 subtype B genome by gamma interferon ELISPOT assay. Kruskal-Wallis nonparametric analysis of variance was used to test significant differences across gene regions, and Tukey pairwise analysis was used to identify differences between gene regions. Spearman rank correlation was used to assess the relation between responses. Results The order of recognized frequencies of specific T lymphocyte responses to HIV proteins was Nef〉Vpr〉Gag〉Pol〉Vpu〉Env〉Rev〉Vif〉Tat. When adjusted for protein length, Nef, Vpr, Gag, and Pol were the most intensely targeted proteins and the central region of Nef, Gag p24, Pol RT, and Vpr was most frequently recognized. No significant correlation was observed between the magnitude of IFN-γ production of HIV-l-specific T lymphocyte responses and plasma viremia, breadth of response and CD4 counts. Conclusion The central region of Nef, Gag p24, Pol RT, and Vpr is most frequently targeted in HIV-1 B/C recombinants chronic infectors. HIV-1-specific T lymphocyte responses and plasma viremia or CD4 counts play no protective role at complete genome level in these infectors.

INTRACELLULAR EXPRESSION OF MULTIMERIZED ANTISENSE TAR-CORE RNAS INHIBIT THE REPLICATION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 IN HUMAN CD_4+T LYMPHOCYTES

Gene therapy is one of several approaches that are being tested in the search for an effective anti HIV treatment. In this strategy, a “resistant” gene would be introduced into target cells, rendering them resistance to the infection of HIV. The HIV 1 Tat protein transactivate HIV 1 gene expression at the transcriptional level by interacting with its response element(TAR) in the long terminal repeat(LTR). Previously, we have shown that antisense polyTAR Core RNAs can inhibit the transactivation of HIV 1 Tat protein in transiently transfected Jurkat cells. To determine whether this antisense polyTAR Core RNAs could inhibit HIV 1 replication in CD 4+ T cells, we transfected the antisense polyTAR Core gene to MT4 cells and challenged them with HIV 1 SF33 strain. Levels of HIV 1 p24gag antigen were reduced more than 4 fold in cultures of the transduced MT4/LR cells infected with HIV 1SF33 strain. In contrast, cultures of nontransduced MT4 cells and control LX vector transduced MT4/LX cells infected with the same viruses had high levels of HIV 1 p24gag. Our work showed that antisense polyTAR Core RNAs were able to inhibit HIV 1 replication in CD 4+ T cells, and could be used as resistance gene in further studying for gene therapy against HIV 1.