Feline immunodeficiency virus (FIV) neutralization: a review

One of the major obstacles that must be overcome in the design of effective lentiviral vaccines is the ability of lentiviruses to evolve in order to escape from neutralizing antibodies. The primary target for neutralizing antibodies is the highly variable viral envelope glycoprotein (Env), a glycoprotein that is essential for viral entry and comprises both variable and conserved regions. As a result of the complex trimeric nature of Env, there is steric hindrance of conserved epitopes required for receptor binding so that these are not accessible to antibodies. Instead, the humoral response is targeted towards decoy immunodominant epitopes on variable domains such as the third hypervariable loop (V3) of Env. For feline immunodeficiency virus (FIV), as well as the related human immunodeficiency virus-1 (HIV-1), little is known about the factors that lead to the development of broadly neutralizing antibodies. In cats infected with FIV and patients infected with HIV-1, only rarely are plasma samples found that contain antibodies capable of neutralizing isolates from other clades. In this review we examine the neutralizing response to FIV, comparing and contrasting with the response to HIV. We ask whether broadly neutralizing antibodies are induced by FIV infection and discuss the comparative value of studies of neutralizing antibodies in FIV infection for the development of more effective vaccine strategies against lentiviral infections in general, including HIV-1.     

The molecular biology of feline immunodeficiency virus (FIV)

Feline immunodeficiency virus (FIV) is widespread in feline populations and causes an AIDS-like illness in domestic cats. It is highly prevalent in several endangered feline species. In domestic cats FIV infection is a valuable small animal model for HIV infection. In recent years there has been sa significant increase in interest in FIV, in part to exploit this, but also because of the potential it has as a human gene therapy vector. Though much less studied than HIV there are many parallels in the replication of the two viruses, but also important differences and, despite their likely common origin, the viruses have in some cases used alternative strategies to overcome similar problems. Recent advances in understanding the structure and function of FIV RNA and proteins and their interactions has enhanced our knowledge of FIV replication significantly, however, there are still many gaps. This review summarizes our current knowledge of FIV molecular biology and its similarities with, and differences from, other lentiviruses.     

Feline immunodeficiency virus in South America

The rapid emergence of AIDS in humans during the period between 1980 and 2000 has led to extensive efforts to understand more fully similar etiologic agents of chronic and progressive acquired immunodeficiency disease in several mammalian species. Lentiviruses that have gene sequence homology with human immunodeficiency virus (HIV) have been found in different species (including sheep, goats, horses, cattle, cats, and several Old World monkey species). Lentiviruses, comprising a genus of the Retroviridae family, cause persistent infection that can lead to varying degrees of morbidity and mortality depending on the virus and the host species involved. Feline immunodeficiency virus (FIV) causes an immune system disease in domestic cats (Felis catus) involving depletion of the CD4+ population of T lymphocytes, increased susceptibility to opportunistic infections, and sometimes death. Viruses related to domestic cat FIV occur also in a variety of nondomestic felids. This is a brief overview of the current state of knowledge of this large and ancient group of viruses (FIVs) in South America.     

Cardiovascular disease in human immunodeficiency virus

With widespread access to high‐quality medical care as in Australia, human immunodeficiency virus (HIV) is now considered a chronic, treatable condition, with a good life expectancy. The use of combined highly active antiretroviral therapy has enabled effective suppression of the virus, but has also been associated with increased cardiac morbidity and mortality. Over representation of traditional cardiac risk factors, such as hyperlipidaemia and diabetes, as well as an increased incidence of ischaemic and non‐ischaemic heart disease is now considered a major concern of treatment with antiretroviral therapy. Therefore, a contemporary management strategy for patients with HIV must include active prevention and treatment of cardiovascular risk. This review will outline the complex interplay between HIV infection, antiretroviral drug regimens and accelerated cardiovascular disease, with a particular focus on screening, prevention and treatment options in a contemporary Australian HIV population.     

Evaluation of different antiretroviral drug protocols on naturally infected feline immunodeficiency virus (FIV) cats in the late phase of the asymptomatic stage of infection

The aim of this study was to evaluate the efficacy of the antiretrovirals: Zidovudine (ZDV) alone; ZDV + Recombinant Human Interferon-α (rHuIFN-α); ZDV + Lamivudine (3TC) and ZDV + valproic acid (Valp) on naturally feline immunodeficiency virus (FIV)-infected cats, in the late phase of the asymptomatic stage of infection. The follow-up was performed over one year, through clinical evaluation and the determination of viral loads and CD4+/CD8+ ratios. Neurological signs were studied by visual and auditory evoked potentials (VEP, AEP) and the responses were abnormal in 80% of the FIV-infected cats. After one year, an improvement in VEP and AEP was observed in the ZDV + Valp group and a worsening in the group receiving ZDV + rHuIFN-α. The CD4+/CD8+ ratio showed a significant increase (both intra and inter-groups) only in ZDV and ZDV + 3TC, between their pre-treatment and one year values, as well as among the other groups. Viral load only showed a significant decrease in ZDV and ZDV + 3TC groups, when comparing the values at one year of treatment vs. pre-treatment values and when the different groups were compared. In addition, the viral load decrease was significantly more pronounced in the ZDV + 3TC vs. ZDV group. We conclude that ZDV and ZDV + 3TC produce significant reductions in viral load and stimulate a recovery of the CD4+/CD8+ ratio, compared with the other protocols. It is clear that the addition of 3TC resulted in a greater reduction in viral load than use of ZDV as a single drug. Therefore, the combination ZDV + 3TC could be more effective than the sole use of ZDV.     

Administration of Fozivudine tidoxil as a single-agent therapeutic during acute feline immunodeficiency virus infection does not alter chronic infection

Initiating combination antiretroviral therapy (ART) during acute HIV infection has been correlated with decreased viral set point and improved lymphocyte function. However, the long term effects of single-agent therapy administered only during the acute stage of infection (interrupted treatment) remain largely uncharacterized. In this study we provide longitudinal data using the feline immunodeficiency virus (FIV) model for HIV infection. Infected cats were treated with a prophylactic single-agent therapy, Fozivudine tidoxil (FZD), for six weeks, starting one day before infection. The initial acute infection study, reported elsewhere, demonstrated a decrease in plasma- and cell-associated viremia at two weeks post-infection (PI) in FZD-treated cats as compared to placebo-treated cats. We hypothesized that this early alteration in plasma- and cell-associated viremia would alter the virus set point and ultimately affect the outcome of chronic infection. Here we provide data at one, two and three years PI for plasma- and/or cell-associated viremia, total lymphocyte counts and CD4:CD8 ratios. There was no difference in viremia or cell counts between treated and nontreated groups at all time points tested. Contrary to our hypothesis, these results suggest that treatment with a single agent anti-retroviral drug during acute lentivirus infection does not significantly alter viral load and immune function during the chronic, asymptomatic stage of infection.     

Highly active antiretroviral therapy improved persistent lamivudine‐resistant viremia in acute hepatitis B virus genotype Ae infection with coinfection of human immunodeficiency virus

A 57‐year‐old man developed acute hepatitis B virus (AHB), caused by HBV genotype Ae. Lamivudine (LAM) therapy was started at 8 months after the disease onset, because the infection was persistent, but not self‐limited. Despite LAM therapy, the hepatitis became chronic. Further, virological breakthrough developed due to the emergence of LAM‐resistant YMDD mutants at 11 months after LAM therapy. Adefovir dipivoxil (ADV) was combined with LAM against breakthrough hepatitis at 28 months after LAM therapy. Sequential genetic analysis revealed that rtL217R, a mutation potentially diminishing the ADV efficacy, was detected before and after the combination therapy. During the follow‐up period, the patient unexpectedly turned out coinfected with human immunodeficiency virus (HIV) by measuring anti‐HIV‐1 antibody. At that time, LAM‐resistant HIV mutation, M184V, had been already detected. We switched from the combination therapy with LAM plus ADV to highly active antiretroviral therapy (HAART), which included tenofovir disoproxil fumarate. HAART drastically improved LAM‐resistant viremia and breakthrough hepatitis as well as HIV viremia and CD4 counts. Even in Japan, HBV genotype and HIV coinfection should be determined early in the treatment of AHB, and early induction of nucleotide analogs should be taken into consideration, because the proportion of AHB patients with HBV genotype A and the number of patients horizontally coinfected with HBV and HIV are increasing.     

Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.     

Human immunodeficiency virus (HIV) associated non-Hodgkin's lymphomas in Denmark: report of three cases

High grade malignant non-Hodgkin's lymphoma (NHL) was the presenting manifestation of the acquired immunodeficiency syndrome (AIDS) in 3/81 reported cases of AIDS in Denmark (by April 2, 1986). Asymptomatic HIV infection, 1 and 5 yr prior to the onset of lymphoma, was documented in 2 cases. 1 patient became infected by Factor VIII treatment, 2 were male homosexuals. 2 patients had an uncommon tumour presentation in the oral cavity, 1 patient presented with an abdominal mass. The histologic subtypes were immunoblastic (2), and small noncleaved cell, Burkitt's (1). Helper/suppressor T-cell ratio was decreased at onset of lymphoma in 2 cases. All 3 patients have died, 4, 6, and 24 months after diagnosis of NHL. Only 1 patient died of NHL, 1 died of an unclassified pneumonia and the third developed progressing supranuclear HIV-associated polyneuropathy without evidence of CNS lymphoma. Thus, high grade malignant B-cell NHL is a regular initial manifestation of AIDS, and may develop after years of asymptomatic HIV infection.     

13例HIV/HBV重叠感染患者的实验指标分析

目的了解艾滋病病毒与乙型肝炎病毒（HIV/HBV）重叠感染患者的临床特征,分析HIV与HBV在疾病进展中的相互作用。方法回顾性分析、比较13例HIV/HBV重叠感染组、28例单纯HIV感染组、28例单纯HBV感染组患者,在免疫功能、肝脏功能及血常规方面的差异。结果免疫功能检测：CD4^＋T细胞计数和CD4^＋/CD8^＋T细胞比值表现为HIV/HBV重叠感染组〈单纯HIV组〈单纯HBV组（P〈0.01）;肝脏功能检测：HIV/HBV重叠感染组与单纯HIV感染组各项指标无显著性差异,而单纯HBV组的丙氨酸氨基转移酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素显著高于（P〈0.01）或高于（P〈0.05）另外两组;血常规检测：HIV/HBV重叠感染组和单纯HIV组各指标无显著性差异,但与单纯HBV组比较,则红细胞和血红蛋白显著降低（P〈0.01）,血小板明显升高（P〈0.01）。结论研究结果初步提示,HIV与HBV重叠感染后,可能减轻患者的肝细胞损伤,进一步降低患者的免疫功能。     

人类免疫缺陷病毒抗体阳性与阴性隐球菌脑膜炎患者临床特点分析

目的分析人类免疫缺陷病毒（HIV）抗体阳性与阴性隐球菌脑膜炎（隐脑）患者的临床特征、治疗及预后。方法收集该院2006-06～2012-06收治的64例隐脑患者的临床资料,按HIV抗体阳性与阴性分为两组,比较分析两组患者的特点。结果两组患者均主要表现为发热、头痛、呕吐,有脑膜刺激征及颅内压升高,HIV阳性组起病较急,发热较明显,从发病到确诊的平均时间短于HIV阴性组,合并机会性感染多。两组脑脊液检查均主要表现为细胞数和蛋白含量升高,葡萄糖和氯化物含量降低,HIV阳性组脑脊液细胞数明显较阴性组少。两组头颅影像学表现主要为脑膜改变及脑积水,累及脑实质多见于HIV阳性患者。两组患者均予两性霉素B单用或联用抗隐球菌治疗,未抗隐球菌治疗及颅内压越高患者病死率高。HIV阳性组死亡17例,阴性组死亡2例,两组病死率比较差异无统计学意义（P〉0.05）。结论两组临床表现、实验室检查结果相似,两性霉素B抗真菌治疗效果较好,早期诊断、积极控制颅内压有助于改善预后。     

高效抗逆转录病毒治疗对人类免疫缺陷病毒感染患者骨密度的影响

目的 评价高效抗逆转录病毒治疗(HAART)对HIV感染患者骨密度(BMD)的影响及其相关因素.方法 收集2007-2008年间50例接受HAART的HIV/MDS患者(治疗组)、12例未用HAART的HIV/AIDS患者(未治疗组)、20例健康对照者(对照组)的临床资料,采用双能X线BMD吸收仪(DEXA)测定BMD以及T值,分别对其数据进行统计分析.结果 治疗组中19例(38.0%)患者发生骨量减少,1例(2.0%)患者发生骨质疏松.对照组中5例(25.0%)发生骨量减少,无骨质疏松者.未治疗组中6例(50.0%)患者发生骨量减少,2例(16.7%)患者发生骨质疏松.未治疗组骨量减少/骨质疏松发生率较对照组显著增高(P=0.02).HIV/AIDS组(包括未治疗组和治疗组)的股骨、股骨颈、大粗隆的BMD[(0.97±0.14)、(0.91±0.13)、(0.76 4-0.12)g/cm2]明显低于对照组[(1.04±0.12)、(0.98±0.14)、(0.84±0.11)g/cm2,P<0.05];而未治疗组和治疗组的BMD差异无统计学意义.治疗组中,骨量减少/骨质疏松与体重<60 kg(r=0.074,P=0.004)、使用HAART前血浆病毒载量(r=5.103,P=0.021)呈正相关.结论 未接受HAART的HIV/AIDS患者较健康人骨量减少/骨质疏松发生率高.HIV/MDS患者BMD较健康人低,接受HAART和未接受HAART治疗的HIV/AIDS患者BMD相当.接受HAART患者中,体重<60 kg、治疗前HIV RNA是发生骨量减少/骨质疏松的危险因素.     

Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease

Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of >0.1 x 10(9) CD4 cells/l and/or at least one viral load <500 copies/ml during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 0.19; 95% confidence interval (CI) 0.06-0.60], complete remission (RH 0.30, 95% CI 0.13-0.72), and age 相似文献   

HEMOCO: a French prospective study of hemophiliacs infected by human immunodeficiency virus type 1 (HIV-1)

HEMOCO is a multicenter prospective cohort set up in 1989 to monitor 407 French hemophiliacs infected by HIV-1 and recruited in 4 hemophilia treatment centers in the Paris region. As of 15 July 1995, 42% of the patients in the cohort had developed stage B HIV disease and 29% stage C disease (AIDS); 23.1% of the patients had died. The cumulative proportion of patients with AIDS was 4.5% at 5 years and 27.4% at 10 years, while the respective mortality rates were 3.8% and 19.5%. In our study, only age was predictive of AIDS, with an estimated relative risk of 1.2 per 10-year age increment; this factor was also predictive of death. After 10 years of follow-up, 6.1% of the study population had no clinical or laboratory signs of immunodepression. The follow-up protocol in the HEMOCO protocol is the same as that in the French SEROCO study, which includes men infected by HIV-1 through sexual contact. This will allow us to compare the progression of HIV infection between these two exposure groups.HEMOCO Study Group: Y Sultan, N Stieltjes: Centre des Hémophiles, Groupe Hospitalier Cochin, Paris; C Gazengel, C Rothschild, M F Torchet: Centre dHémobiologie Transfusion Paris Ouest, Hôpital Necker Enfants Malades, Paris; Y Laurian, A Blanc, R dOiron, A Rafowicz, L Kebedjis: Centre de Traitement de lHémophilie, Hôpital du Kremlin-Bicêtre, Le Kremlin-Bicêtre; J Peynet, C Laux: Centre de Transfusion des Yvelines, Centre de Traitement de lHémophilie, Centre Hospitalier de Versailles, Le Chesnay     

Highly active antiretroviral therapy used to treat concurrent hepatitis B and human immunodeficiency virus infections

We report a case of simultaneous infection with hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) in a 26-year-old Japanese homosexual man. He was admitted to our hospital for acute hepatitis caused by HBV. At that time, HIV-1-antibody (Ab) was not detected in his serum. After 6 months, he was readmitted to our hospital for further examination of his liver because of confined liver enzyme abnormalities. Anti-HIV-1 Ab was detected in his serum by both enzyme immunosorbent assay (EIA) and particle agglutination (PA). His serum HIV-1 RNA level was 50 × 10⁴ copies/ml and serum levels of HBV DNA polymerase (DNA-P) and HBV DNA were 6535 cpm and 3 plus (>1000 copies/ml). His clinical course and laboratory data suggested progression from acute to chronic hepatitis related to coinfection with HIV-1. The diagnosis was chronic active hepatitis caused by HBV as an opportunistic infection due to coinfection with HIV-1. We began highly active antiretroviral therapy (HAART) because interferon (IFN) therapy was ineffective. HAART was started at an initial dosage of 600 mg zidovudine (AZT), 300 mg lamivudine (3TC), and 2400 mg indinavir (IDV) daily. After 4 weeks, the serum level of HBV DNA-polymerase (p) had decreased markedly to 37 cpm and that of HIV-1 RNA had decreased to below the sensitivity threshold, indicating considerable suppression of the replication of these viruses by the treatment. But HBV DNA remained at low levels. Although the incidence of HBV infection in patients with HIV-1 infection has been reported to be high in the United States and Europe, simultaneous HBV and HIV-1 infection leading to persistent HBV infection is rare. (Received Feb. 13, 1998; accepted Sept. 25, 1998)     

Human immunodeficiency virus associated thrombotic thrombocytopenic purpura--favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy

Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder. Human immunodeficiency virus (HIV) is an identified precipitant. This study reviewed 30 episodes of HIV-associated TTP in 24 patients from the South-East England Apheresis units, over the last 10 years. All patients were heterosexual Black Africans. First presentation of TTP revealed a new diagnosis of HIV in eight patients. TTP relapse occurred on six occasions (in four patients) as a result of non-adherence to highly active antiretroviral therapy (HAART). Prompt initiation/re-initiation of HAART in parallel with plasma exchange (PEX)±steroid led to prompt remission. Adjunct immunomodulatory agents (e.g. Rituximab) were required in 10% of cases. Once-daily HAART regimens are recommended, being compatible with PEX requirement, maximizing drug exposure between PEX. High viral loads (>500,000 copies/ml) require more PEX to remission. ADAMTS13 activity was reduced (<5%) as detected by collagen-binding assay and anti-ADAMTS13 immunoglobulin G antibodies were raised in 80%. Continued HAART-adherence ensured a durable TTP remission with associated viral control resulting in no evidence of relapse. PEX and HAART are associated with replenishment of ADAMTS13 and viral suppression. More PEX is required in cases with higher viral loads. Continued HAART maintains remission. In a small proportion of cases, further immunomodulatory therapy may be required.