Showing papers in "Current HIV Research in 2019"
TL;DR: HIV incidence in Guangxi has stabilized, due in part to HIV prevention efforts that include expanded HIV testing, antiretroviral treatment, and other intervention measures, and no longer appear to be increasing.
Abstract: The aim of this review is to describe long-term HIV epidemiology and prevention trends in Guangxi, a provincial-level region located along a major drug trafficking corridor in southwestern China. Between 1996 and 2006, HIV transmission in Guangxi was primarily fueled by Injection Drug Use (IDU). Since 2006, heterosexual sex has become the dominant mode of HIV transmission, followed by drug injection. Moreover, older, heterosexual adults appear to be at increased risk for HIV. The vast majority of new HIV cases are attributed to local HIV subtypes already circulating within Guangxi (93%), though imported subtypes are associated with younger age groups. Since 2011, HIV incidence in Guangxi has stabilized, due in part to HIV prevention efforts that include expanded HIV testing, antiretroviral treatment, and other intervention measures. Between 1996 and 2017, Guangxi, China experienced dramatic changes in the primary HIV transmission mode and at-risk age group. Due in part to local and National AIDS control and prevention campaigns, HIV incidence trends in Guangxi no longer appear to be increasing.
37 citations
TL;DR: In the HIV population, for many NADCs prognosis is still worse as compared to the general population, however, an improvement has been reported over the last decades, mainly thanks to more available and adequate treatment chances.
Abstract: The advent of highly active antiretroviral therapy (HAART) has significantly reduced the incidence of AIDS events, including AIDS-defining malignancies. Nevertheless, several cohort studies conducted in the post-HAART period have reported an increasing risk of non-AIDS-defining cancers (NADC). Overall, the potential mechanisms leading to an increased risk of developing NADCs probably involve multiple known and unknown factors. In addition to ageing, chronic inflammation and ongoing immune system dysregulation, other contributing factors are co-infection with potentially oncogenic viruses (HBV, HCV, HPV, EBV) and high-risk behaviours such as tobacco smoking. As a consequence of these risk factors, high standardized incidence ratios have been consistently reported, mainly in cohort studies regarding smoking-related cancers (lung cancer, but also pharyngeal and kidney cancer), due to the far more common cigarette smoking habit in the HIV-population. Also in the setting of infection-related malignancies, the high frequency of liver cancer, as a consequence of HBV and HCV co-infection is well known. Similarly, HPV infection accounts for the higher risk of anal cancer. On the same line, Hodgkin lymphoma is more frequent in the HIV population, due to the dysregulation and proliferation of EBV-infected lymphocytes. Several studies addressed the direct relationship between immunosuppression and cancer progression, showing that subjects with HIV infection experience higher cancer-specific mortality, as compared to the general population, independently of cancer stage or cancer treatment. In the HIV population, for many NADCs, the prognosis is still worse as compared to the general population. However, an improvement has been reported over the last decades, mainly thanks to more available and adequate treatment chances.
35 citations
TL;DR: Routine monitoring of hemoglobin levels and prompt management of anemia in all pa-tients on ART as a strategy to improve virologic success rates is recommended.
Abstract: Background Adverse drug reactions (ADRs) associated with antiretroviral therapy (ART) can rapidly reverse the gains of ART resulting in poor health outcomes. We need an improved understanding of specific ART-related ADRs that influence virologic outcomes. Objective To investigate the frequency of clinical ADRs and assess their effect on virologic failure in patients on ART. Method We described the prevalence of major clinical ADRs, and the association between specific ADRs and virologic failure in a clinic cohort of HIV-1 infected Nigerians aged ≥18 years, on firstline ART between June 2004 and February 2012. Multivariable logistic regression was run to identify predictors of virologic failure at 24 and 72 weeks of ART. Results Data of 12,115 patients with a median age of 34 (interquartile range: 29-41) years, and predominantly females (67%) were evaluated. Overall, 957 (7.9%) patients experienced at least one ADR during a median follow-up period of 4 years (interquartile range: 1-7). The three most prevalent ADRs were lipodystrophy (2.6%), anemia (1.9%), and skin rash (0.7%). Virologic failure rate was 36% and 34% at 24 and 72 weeks of ART, respectively. Anemia independently predicted the odds of virologic failure at 72 weeks of ART (adjusted odds ratio, 1.74; 95% CI: 1.2-2.51); adjusted for sex, age, pre-treatment CD4+ cell count, antiretroviral regimen, and medication refill adherence. Conclusion Antiretroviral therapy-associated anemia increases the likelihood of late virologic failure. We recommend routine monitoring of hemoglobin levels and prompt management of anemia in all patients on ART as a strategy to improve virologic success rates.
19 citations
TL;DR: Among several methods applying in studied clinical trials which are mainly divided to DNA, Protein, Peptide, Viral vectors and Dendritic cell based vaccines, protein vaccine strategy which is based on Tat protein induced anti-Tat Abs is found in 79% HIV patients.
Abstract: Background Among the various types of pharmaceuticals, vaccines have a special place. However, in the case of HIV, nearly after 40 years of its discovery, an effective vaccine still is not available. The reason lies in several facts mainly the variability and smartness of HIV as well as the complexity of the interaction between HIV and immune responses. A robust, effective, and longterm immunity is undoubtedly what a successful preventive vaccine should induce in order to prevent the infection of HIV. Failure of human trials to this end has led to the idea of developing therapeutic vaccines with the purpose of curing already infected patients by boosting their immune responses against the virus. Nevertheless, the exceptional ability of the virus to escape the immune system based on the genetically diverse envelope and variable protein products have made it difficult to achieve an efficient therapeutic vaccine. Objective We aimed at studying and comparing different approaches to HIV therapeutic vaccines. Methods In this review, we summarized the human trials undergoing on HIV therapeutic vaccination which are registered in the U.S. clinical trial database (clinicaltrials.gov). These attempts are divided into different tables, according to the type of formulation and application in order to classify and compare their results. Result/conclusion Among several methods applied in studied clinical trials which are mainly divided into DNA, Protein, Peptide, Viral vectors, and Dendritic cell-based vaccines, protein vaccine strategy is based on Tat protein-induced anti-Tat Abs in 79% HIV patients. However, the studies need to be continued to achieve a durable efficient immune response against HIV-1.
19 citations
TL;DR: This short re-view focuses on gp120 neurotropism and associated mechanisms of neurotoxicity linked to chemokine receptors CCR5 and CXCR4 with a new perspective on plasma membrane lipid rafts as an active par-ticipant in gp120-mediated neurodegeneration underlying HIV induced CNS pathology.
Abstract: The implementation of combination antiretroviral therapy (cART) as the primary means of treatment for HIV infection has achieved a dramatic decline in deaths attributed to AIDS and the reduced incidence of severe forms of HIV-associated neurocognitive disorders (HAND) in infected individuals. Despite these advances, milder forms of HAND persist and prevalence of these forms of neurocognitive impairment are rising with the aging population of HIV infected individuals. HIV enters the CNS early in the pathophysiology establishing persistent infection in resident macrophages and glial cells. These infected cells, in turn, secrete neurotoxic viral proteins, inflammatory cytokines, and small metabolites thought to contribute to neurodegenerative processes. The viral envelope protein gp120 has been identified as a potent neurotoxin affecting neurodegeneration via indirect and direct mechanisms involving interactions with chemokine co-receptors CCR5 and CXCR4. This short review focuses on gp120 neurotropism and associated mechanisms of neurotoxicity linked to chemokine receptors CCR5 and CXCR4 with a new perspective on plasma membrane lipid rafts as an active participant in gp120-mediated neurodegeneration underlying HIV induced CNS pathology.
15 citations
TL;DR: Lopinavir SLN based gel was found to have modified drug release pattern providing sustained release as compared to plain drug gel, which indicates that LopinavIR when given topically has a good potential to target the HIV asCompared to when given orally.
Abstract: Background Lopinavir is a specific reversible inhibitor of the enzyme HIV protease with mean oral bioavailability of less than 20 % due to extensive hepatic metabolism by cytochrome P450 3A4. The reported half-life of Lopinavir is 5-6 hours and the maximum recommended daily dose is 400 mg/day. All the marketed tablet and capsule formulations of lopinavir are generally combined with Ritonavir, a potent inhibitor of cytochrome P450 3A4, to minimize presystemic metabolism of lopinavir. Hence, to overcome limitations associated with oral administration of lopinavir and to promote single drug administration, utilization of vesicular nanocarriers through topical route could prove to be effective, as the approach combines the inherent advantages of topical route and the drug-carrying potential of vesicular nanocarriers across the tough and otherwise impervious skin barrier layer, i.e., stratum corneum. Objective The objective was to develop solid lipid nanoparticles (SLN) of lopinavir and formulate a topical gel for improved systemic bioavailability of lopinavir. Method SLNs were prepared using high-pressure homogenization technique and optimized. The nanoparticles were characterized by SEM to confirm their spherical shape. Differential Scanning Calorimetry (DSC) analysis was carried out to ensure the entrapment of drug inside the SLNs. A comparative evaluation was done between SLN based gel and plain gel of drug by performing exvivo skin permeation studies using Franz diffusion cell. To explore the potential of topical route, invivo bioavailability study was conducted in male Wistar rats. Results The optimized formulation composed of Compritol 888ATO (0.5 %) as a lipid, Poloxamer 407 (0.25 %) as a surfactant and Labrasol (0.25 %) as a co-surfactant gave the maximum entrapment of 69.78 % with mean particle size of 48.86nm. The plain gel of the drug gave a release of 98.406 ± 0.007 % at the end of 4hours whereas SLN based gel gave a more sustained release of 71.197 ±0.006 % at the end of 12hours ex-vivo. As observed from the results of in-vivo studies, highest Cmax was found with SLN based gel (20.3127 ± 0.6056) µg/ml as compared to plain gel (8.0655 ± 1.6369) µg/ml and oral suspension (4.2550 ± 16.380) µg/ml of the drug. Also, the AUC was higher in the case of SLN based gel indicating good bioavailability as compared to oral suspension and plain gel of drug. Conclusion Lopinavir SLN based gel was found to have modified drug release pattern providing sustained release as compared to plain drug gel. This indicates that Lopinavir when given topically has a good potential to target the HIV as compared to when given orally.
13 citations
TL;DR: The predicted fusion protein, p24-AAY-Nef in a truncated form with a high rate of T cell epitopes and high conservancy rate among different clades, provides a helpful model for developing a therapeutic vaccine candidate against HIV-1.
Abstract: Background Acquired immune deficiency syndrome (HIV/AIDS) has been a major global health concern for over 38 years. No safe and effective preventive or therapeutic vaccine has been developed although many products have been investigated. Computational methods have facilitated vaccine developments in recent decades. Among HIV-1 proteins, p24 and Nef are two suitable targets to provoke the cellular immune response. However, the fusion form of these two proteins has not been analyzed in silico yet. Objective This study aimed at the evaluation of possible fusion forms of p24 and Nef in order to achieve a potential therapeutic subunit vaccine against HIV-1. Method In this study, various computational approaches have been applied to predict the most effective fusion form of p24-Nef including CTL (Cytotoxic T lymphocytes) response, immunogenicity, conservation and population coverage. Moreover, binding to MHC (Major histocompatibility complex) molecules was assessed in both human and BALB/c. Results After analyzing six possible fusion protein forms using AAY linker, we came up with the most practical form of p24 from 80 to 231 and Nef from 120 to 150 regions (according to their reference sequence of HXB2 strain) using an AAY linker, based on their peptides affinity to MHC molecules which are located in a conserved region among different virus clades. The selected fusion protein contains seventeen MHC I antigenic epitopes, among them KRWIILGLN, YKRWIILGL, DIAGTTSTL and FPDWQNYTP are fully conserved between the virus clades. Furthermore, analyzed class I CTL epitopes showed greater affinity binding to HLA-B 57*01, HLA-B*51:01 and HLA-B 27*02 molecules. The population coverage with the rate of >70% coverage in the Persian population supports this truncated form as an appropriate candidate against HIV-I virus. Conclusion The predicted fusion protein, p24-AAY-Nef in a truncated form with a high rate of T cell epitopes and high conservancy rate among different clades, provides a helpful model for developing a therapeutic vaccine candidate against HIV-1.
13 citations
TL;DR: A mechanism by which tobacco use impairs HIV antiretroviral therapy to increase intracellular drug concentrations in this important cellular reservoir is suggested.
Abstract: BACKGROUND Cigarette smoking increases systemic oxidative stress, inflammation, and viral replication in individuals with HIV. Macrophages are infected during HIV infection and serve as an important reservoir throughout the process. Macrophages exist in two phenotypes, the classically activated M1 macrophage and alternatively activated M2 macrophage. The expression of drug efflux transporters and metabolic enzymes, which have direct effects on intracellular drug concentrations, differ between the pro-inflammatory M1 macrophage and the anti-inflammatory M2 macrophage. OBJECTIVE To further explain the role of tobacco use in worsened outcomes in the HIV + population receiving antiretroviral therapy. METHODS Western blotting was used to examine macrophage polarization and expression of drug efflux transporters, CYP enzymes, and antioxidant enzymes. The arginase assay was used to measure arginase activity. Cytokine production was measured using the human multiplex inflammatory cytokine assay kit. The 8-OHdG DNA Damage Quantification Direct Kit was used to quantify DNA damage. Viral replication under the influence of tobacco and antiretroviral drug use was measured by p24 Elisa. RESULTS We observed phenotypic shifts from M1 to M2 with both individual and combination treatments with cigarette smoke condensate and the protease inhibitor antiretroviral drug lopinavir. These shifts lead to changes in cytokine production, the expression of CYP enzymes, anti-oxidant enzymes, and drug efflux transporters, as well as changes in viral replication. CONCLUSION This data suggest a mechanism by which tobacco use impairs HIV antiretroviral therapy to increase intracellular drug concentrations in this important cellular reservoir.
12 citations
TL;DR: The available evidence does not provide conclusive support for the existence of a clear association with adherence to ART among HIV patients, and among socio-economic factors, the determinant of socioeconomic and demographic statuses was not found to be significantly associated with adherence in studies related to income.
Abstract: Background Socioeconomic and demographic statuses are associated with adherence to the treatment of patients with several chronic diseases. However, there is a controversy regarding their impact on adherence among HIV/AIDS patients. Thus, we performed a systematic review of the evidence regarding the association of socioeconomic and demographic statuses with adherence to antiretroviral therapy (ART) among HIV/AIDS patients. Methods The PubMed database was used to search and identify studies concerning about socioeconomic and demographic statuses and HIV/AIDS patients. Data were collected on the association between adherence to ART and varies determinants factors of socioeconomic (income, education, and employment/occupation) and socio-demographic (sex and age). Findings From 393 potentially-relevant articles initially identified, 35 original studies were reviewed in detail, which contained data that were helpful in evaluating the association between socioeconomic/ demographic statuses and adherence to ART among HIV patients. Two original research study has specifically focused on the possible association between socioeconomic status and adherence to ART. Income, level of education, and employment/occupational status were significantly and positively associated with the level of adherence in 7 studies (36.8%), 7 studies (28.0%), and 4 studies (23.5%) respectively out of 19, 25, and 17 studies reviewed. Sex (being male), and age (per year increasing) were significantly and positively associated with the level of adherence in 5 studies (14.3%), and 9 studies (25.7%) respectively out of 35 studies reviewed. However, the determinant of socioeconomic and demographic statuses was not found to be significantly associated with adherence in studies related to income 9(47.4%), education 17(68.0%), employment/ occupational 10(58.8%), sex 27(77.1%), and age 25(71.4%). Conclusion The majority of the reviewed studies reported that there is no association between socio- demographic and economic variables and adherence to therapy. Whereas, some studies show that age of HIV patients (per year increasing) and sex (being male) were positively associated with adherence to ART. Among socio-economic factors, the available evidence does not provide conclusive support for the existence of a clear association with adherence to ART among HIV patients. There seems to be a positive trend between socioeconomic factors and adherence to ART in some of the reviewed studies.
12 citations
TL;DR: Frailty is a common occurrence among HIV-infected patients under antiretroviral therapy in Indonesia, with depression as an independent predictive factor.
Abstract: Background Increasing age of HIV-1 infected population brought about the risk of frailty as comorbidity, whose prevalence is higher in low and middle-income countries (LMICs). Indonesia as an LMIC also bears a major burden of HIV-1 epidemic with a similarly aging population, but the prevalence of frailty and its predictors are unknown. Objectives To identify the prevalence of frailty and analyze its associated factors, among HIV-1 infected adults under antiretroviral therapy in Indonesia. Methods A cross-sectional study was conducted among HIV-infected individuals with inclusion criteria of age ≥30 years old and underwent ART for at least 6 months. The main assessment was done using Fried's frailty phenotype score, which categorizes subjects into non-frail, pre-frail, or frail. Factors associated with frailty were characterized and multiple logistic regression analysis was performed. Results A total of 164 subjects were recruited; male subjects were 118 (72%), the median age was 40.5 years old, and the median CD4 nadir was 53 cells/μl. Frailty was identified among 90 (54.9%) subjects with 84 (51.2%) identified as pre-frail and 6 (3.7%) as frail, with dominant frailty phenotype was weakness in grip strength. The multivariate model showed that depression was the only factor significantly correlated with pre-frailty and frailty (OR 2.14; 95% CI 1.04-4.43, p=0.036). Conclusion Frailty is a common occurrence among HIV-infected patients under ART, with depression as an independent predictive factor.
12 citations
TL;DR: Patients with HIV/AIDS who initiated lopinavir/ritonavir LPV/r or efavirenz (EFV)-based antiretroviral treatment regimens had increased odds of dyslipidemia, and there was no obvious effect on LDL-C, which is more relevant to the development of cardiovascular disease.
Abstract: BACKGROUND Antiretroviral therapy (ART) is associated with lipid abnormalities that contribute to increased risk of cardiovascular (CV) events among patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Although disorders of lipid metabolism associated with ART have been described before in developed countries, data on lipid profile disorders associated with ART use in China are limited. This study aimed to examine the changes in lipid profile among patients with HIV/AIDS who initiated lopinavir/ritonavir LPV/r or efavirenz (EFV)-based antiretroviral treatment regimens, which continue to be widely used China and other developing countries. METHODS This is a retrospective, matched case-control study of HIV-positive patients initiating either LPV/r or EFV regimens at the Beijing You'an Hospital, Capital Medical University between July 2012 and January 2017. Generalized estimating equations were used to compare the differences in total cholesterol [TC], triglycerides [TG], low-density lipoprotein-cholesterol [LDL-C], and highdensity lipoprotein-cholesterol [HDL-C] at baseline and up to 24-months after ART initiation between the two treatment arms. RESULTS Baseline characteristics, including age, sex, CD4 cell count, viral load, and serum lipids, which were comparable between the two groups. The LPV/r-based regimen group had increased TC, TG, HDL-C, and LDL-C after 24-months of treatment. In the EFV-regimen group, TC, HDL-C, and LDL-C were increased compared to baseline, while the TC/HDL-C ratio decreased, and TG did not change significantly. After 24-months of treatment, the percentage of patients with dyslipidemia in the LPV/r group was much higher than in the EFV group (84.0% vs. 52.6%, P<0.001), and 17(10%) patients on LPV/r-based regimens had severe dyslipidemia. Patients on LPV/r-based regimens were at increased odds of hypercholesterolemia (odds ratio [OR]=1.709, P=0.038), hypertriglyceridemia (OR=4.315, P<0.001), and high TC/HDL-C ratio (OR=1.951, P=0.003). However, no significant difference was found in HDL-C (OR=1.246, P=0.186) or LDL-C (OR=1.253, P=0.410) between the treatment groups. CONCLUSION Both LPV/r or EFV treatment regimens impacted patients' lipid profiles. Compared to EFV-based regimens, patients on LPV/r-based regimens had increased odds of dyslipidemia, such as hypercholesterolemia, hypertriglyceridemia, or high TC/HDL-C ratio; however, there was no obvious effect on LDL-C, which is more relevant to the development of the cardiovascular disease.
TL;DR: The evidence for the role of the gut microbiota in intestinal homeostasis, its contribution to HIV pathogenesis, as well as its use in the development of therapeutic strategies are reviewed.
Abstract: During HIV infection, massive destruction of CD4+ T cells ensues, preferentially depleting the Th17 subset at the gut-associated lymphoid tissue (GALT), leading to a loss of mucosal integrity and an increase in cell permeability. This process favors microbial translocation between the intestinal lumen and the circulatory system, contributing to persistent immune activation and chronic inflammation characteristic of HIV infection. Thus, the gut microbiota plays an integral role in maintaining the structure and function of the mucosal barrier, a critical factor for immune homeostasis. However, in the context of HIV infection, changes in the gut microbiota have been reported and have been linked to disease progression. Here, we review evidence for the role of the gut microbiota in intestinal homeostasis, its contribution to HIV pathogenesis, as well as its use in the development of therapeutic strategies.
TL;DR: It is found that short isoform Per-1 can restrict HIV-1 replication and Tat ameliorates this in-hibitory effect, which may contribute to HIV- 1 latency in resting CD4+ T-cells.
Abstract: Background Understanding of the restriction of HIV-1 transcription in resting CD4+ Tcells is critical to find a cure for AIDS. Although many negative factors causing HIV-1 transcription blockage in resting CD4+ T-cells have been found, there are still unknown mechanisms to explore. Objective To explore the mechanism for the suppression of de novo HIV-1 transcription in resting CD4+ T-cells. Methods In this study, a short isoform of Per-1 expression plasmid was transfected into 293T cells with or without Tat's presence to identify Per-1 as a negative regulator for HIV-1 transcription. Silencing of Per-1 was conducted in resting CD4+ T-cells or monocyte-derived macrophages (MDMs) to evaluate the antiviral activity of Per-1. Additionally, we analyzed the correlation between Per-1 expression and viral loads in vivo, and silenced Per-1 by siRNA technology to investigate the potential anti-HIV-1 roles of Per-1 in vivo in untreated HIV-1-infected individuals. Results We found that short isoform Per-1 can restrict HIV-1 replication and Tat ameliorates this inhibitory effect. Silencing of Per-1 could upregulate HIV-1 transcription both in resting CD4+ Tcells and MDMs. Moreover, Per-1 expression is inversely correlated with viral loads in Rapid progressors (RPs) in vivo. Conclusion These data together suggest that Per-1 is a novel negative regulator of HIV-1 transcription. This restrictive activity of Per-1 to HIV-1 replication may contribute to HIV-1 latency in resting CD4+ T-cells.
TL;DR: Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM, which indicated that synthesized compounds can interact with the key residues of the HIV- 1 integrase active site.
Abstract: Background Although major efforts have been devoted to the effective treatment of HIV-1 infection, it has remained one of the leading causes of deaths around the world. So, development of anti-HIV-1 agents featuring novel structure is essential. Objective To synthesize novel quinazolinone derivatives and evaluate their anti-HIV-1 activity. Method In this study, we designed and synthesized a series of novel 2,3-diaryl-4-quinazolinone derivatives using a one-pot multicomponent reaction. Then, the resulting derivatives were evaluated for anti-HIV-1 activity using Hela cell-based single-cycle replication assay. Results Most of the compounds showed efficacy against HIV-1 replication and the compound 9c exhibited the highest activity with EC50 value of 37 μM. Docking studies indicated that synthesized compounds can interact with the key residues of the HIV-1 integrase active site. Binding of the most active compound was consistent with the HIV-1 integrase inhibitors. Conclusion Based on our results, these derivatives represent novel lead compounds for the development of new promising anti-HIV-1 agents.
TL;DR: This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.
Abstract: BACKGROUND Several approaches have not been successful to suppress HIV (Human immunodeficiency virus) infection among infected individuals or to prevent it yet. In order to expand strong HIV specific humoral and cellular responses, Virus-like particles (VLPs) as potential vaccines show significant increase in neutralizing antibodies secretion, T-cell count and also secretion of cytokines. OBJECTIVE This study aimed at immunological evaluation of VLPs harboring high copy of MPERV3 in BALB/c mice. METHODS Female BALB/c mice were immunized with homologous and heterologous primeboosting regimens of HIV-1 VLPMPER-V3. Their immune responses were evaluated for humoral responses (Total IgG and IgG isotyping) and cellular responses (IFN-γ, IL-5 secretion, in vitro CTL assay and T cell proliferation) and compared in immunized mice. RESULTS The data showed robust induction of humoral response in mice groups which received different regimens of VLP. Furthermore, analysis of cytokine profile indicated that the highest IL-5 secretion was related to VLP+M50 group and confirmed the dominance of Th2 immunity in this group. CONCLUSION This study showed that VLP MPER-V3 as a potential vaccine candidate has the potency as an effective prophylactic vaccine and this finding guarantees further investigations to achieve a promising HIV-1 vaccine candidate.
TL;DR: It is suggested that M918 CPP can be used to enter HIV-1 Nef and Hsp20-Nef pro-teins inside mammalian cells efficiently as a promising approach in HIV- 1 vaccine development.
Abstract: BACKGROUND HIV-1 Nef protein is a possible attractive target in the development of therapeutic HIV vaccines including protein-based vaccines. The most important disadvantage of protein-based vaccines is their low immunogenicity which can be improved by heat shock proteins (Hsps) as an immunomodulator, and cell-penetrating peptides (CPPs) as a carrier. METHODS In this study, the HIV-1 Nef and Hsp20-Nef proteins were generated in E.coli expression system for delivery into the HEK-293T mammalian cell line using a novel cell-penetrating peptide, M918, in a non-covalent fashion. The size, zeta potential and morphology of the peptide/protein complexes were studied by scanning electron microscopy (SEM) and Zeta sizer. The efficiency of Nef and Hsp20-Nef transfection using M918 was evaluated by western blotting in HEK-293T cell line. RESULTS The SEM data confirmed the formation of discrete nanoparticles with a diameter of approximately 200-250 nm and 50-80 nm for M918/Nef and M918/Hsp20-Nef, respectively. The dominant band of ~ 27 kDa and ~ 47 kDa was detected in the transfected cells with the Nef/ M918 and Hsp20-Nef/ M918 nanoparticles at a molar ratio of 1:20 using anti-HIV-1 Nef monoclonal antibody. These bands were not detected in the un-transfected and transfected cells with Nef or Hsp20- Nef protein alone indicating that M918 could increase the penetration of Nef and Hsp20-Nef proteins into the cells. CONCLUSION These data suggest that M918 CPP can be used to enter HIV-1 Nef and Hsp20-Nef proteins inside mammalian cells efficiently as a promising approach in HIV-1 vaccine development.
TL;DR: ZFN, TALEN and CRISPR/Cas9 gene-editing technology has appeared as a promising solution that mimics the natural occurring C CR5/Δ32 mutation and then permanently guarantees the absence of CCR5-expression on HIV target-cells surface, leading to a continuous resistance to the virus entry and, ultimately, proving that cellular immunization from infection could be, in fact, a conceivable therapeutic approach to finally achieve the long-awaited HIV functional cure.
Abstract: Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), is a life-threatening disorder that persists worldwide as a severe health problem. Since it was linked with the HIV attachment process, the Chemokine receptor, CCR5, has been at the development leading edge of several gene-based therapies. Given the shortcomings of the current antiretroviral treatment procedure and the non-availability of a licensed vaccine, the aptitude to modify complex genomes with Designer Nucleases has had a noteworthy impact on biotechnology. Over the last years, ZFN, TALEN and CRISPR/Cas9 gene-editing technology have appeared as a promising solution that mimics the naturally occurring CCR5/Δ32 mutation and permanently guarantees the absence of CCR5-expression on the surface of HIV target-cells, leading to a continuous resistance to the virus entry and, ultimately, proving that cellular immunization from infection could be, in fact, a conceivable therapeutic approach to finally achieve the long-awaited functional cure of HIV.
TL;DR: This study demonstrates a change in the genetic diversity of HIV-1 in the Krasnoyarsk region, which was at the beginning of the epidemic, subtype A6 prevailed, subtypes B and CRF063_02A appeared in the region later.
Abstract: Background The information about the dynamics of the viral population and migration events that affect the epidemic in different parts of the Russia is insufficient. Possibly, the huge size of the country and limited transport accessibility to certain territories may determine unique traits of the HIV-1 evolutionary history in different regions. Objective The aim of this study was to explore the genetic diversity of HIV-1 in the Krasnoyarsk region and reconstruct spatial-temporal dynamics of the infection in the region. Methods The demographic and virologic data from 281 HIV-infected individuals in Krasnoyarsk region collected during 2011-2016 were analyzed. The time to the most recent common ancestor, evolutionary rates, population growth, and ancestral geographic movements was estimated using Bayesian coalescent-based methods. Results The study revealed moderate diversity of the HIV-1 subtypes found in the region, which included A6 (92.3%), CRF063_02A (4.3%), B (1.1%), and unique recombinants (2.5%). Phylogenetic reconstruction revealed that the A6 subtype was introduced into Krasnoyarsk region by one viral lineage, which arose around 1996.9 (1994.5-1999.5). The phylogeography analysis pointed to Krasnoyarsk city as the geographical center of the epidemic, which further spread to central neighboring districts of the region. At least two epidemic growth phases of subtype A6 were identified which included exponential growth in early-2000s followed by the decline in the mid/late 2010s. Conclusion This study demonstrates a change in the genetic diversity of HIV-1 in the Krasnoyarsk region. At the beginning of the epidemic, subtype A6 prevailed, subtypes B and CRF063_02A appeared in the region later.
TL;DR: In silico screening studies and in vitro cell line studies elucidate possible binding mode of phytopolyphenols, which pinpoints their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.
Abstract: Background Lack of effective early-stage HIV-1 inhibitor instigated the need for screening of novel gp120-CD4 binding inhibitor. Polyphenols, a secondary metabolite derived from natural sources are reported to have broad spectrum HIV-1 inhibitory activity. However, the gp120-CD4 binding inhibitory activity of polyphenols has not been analysed in silico yet. Objectives To establish the usage of phytopolyphenols (Theaflavin, Epigallocatechin (EGCG), Ellagic acid and Gallic acid) as early stage HIV-1 inhibitor by investigating their binding mode in reported homology of gp120-CD4 receptor complex using in silico screening studies and in vitro cell line studies. Methods The in silico molecular docking and molecular simulation studies were performed using Schrodinger 2013-2 suite installed on Fujitsu Celsius Workstation. The in vitro cell line studies were performed in the TZM-bl cell line using MTT assay and β-galactosidase assay. Results The results of molecular docking indicated that Theaflavin and EGCG exhibited high XP dock score with binding pose exhibiting Van der Waals interaction and hydrophobic interaction at the deeper site in the Phe43 cavity with Asp368 and Trp427. Both Theaflavin and EGCG form a stable complex with the prepared HIV-1 receptor and their binding mode interaction is within the vicinity 4 A. Further, in vitro cell line studies also confirmed that Theaflavin (SI = 252) and EGCG (SI = 138) exert better HIV-1 inhibitory activity as compared to Ellagic acid (SI = 30) and Gallic acid (SI = 34). Conclusion The results elucidate a possible binding mode of phytopolyphenols, which pinpoints their plausible mechanism and directs their usage as early stage HIV-1 inhibitor.
TL;DR: A subcellular proteomic study in HIV latent cell lines to identify proteins related to HIV latency and one of the differential proteins was verified by western blotting to be down- regulated in two cell lines and HIV resting CD4+ T cells negatively selected from patients.
Abstract: Background Due to the persistence of latent HIV-infected cellular reservoirs, HIV virus can not be eradicated completely. Objective To identify proteins related to HIV latency, we performed a subcellular proteomic study in HIV latent cell lines. Methods An established HIV-1 latent cell model (J-Lat Tat-GFP Clone A7 cells, A7 cells) and its parental cell line (Jurkat cells) were used. The plasma membrane (PM) fraction from cultured cells was enriched through aqueous two-phase partition. PM proteins were extracted and then separated using two-dimensional electrophoresis (2DE). Differentially expressed proteins were identified by mass spectrometry, and verified by western blotting. Results Thirteen non-redundant proteins were identified to be differentially expressed in the A7 PM fraction compared to those in the Jurkat PM. Eight had a PM location through Gene Ontology (GO) analysis. A differential protein network of CAPG-ACTR3-CD3D was detected to have interactions with HIV Vpr, Tat, gp160, etc. through STRING software analysis. One of the differential proteins (Macrophage-capping protein (CAPG)) was verified by western blotting to be down- regulated in two cell lines and HIV resting CD4+ T cells negatively selected from patients. Conclusion We identified 13 proteins in A7 compared to Jurkat cells. CAPG may be a potential biomarker related to HIV latency.
TL;DR: The results suggest that TAT expression may differentially affect brain reward function, dependent on the pattern of methamphetamine exposure, while the subtle effects observed in these studies highlight that longer-term TAT expressions may be more consequential at inducing behavioral and neurochemical effects.
Abstract: Background: Methamphetamine abuse and human immunodeficiency virus (HIV) are common comorbidities. HIV-associated proteins, such as the regulatory protein TAT, may contribute to brain reward dysfunction, inducing an altered sensitivity to methamphetamine reward and/or withdrawal in this population.Objective: These studies examined the combined effects of TAT protein expression and, chronic and binge methamphetamine regimens on brain reward function.Methods: Transgenic mice with inducible brain expression of the TAT protein were exposed to either saline, a chronic, or a binge methamphetamine regimen. TAT expression was induced via doxycycline treatment during the last week of methamphetamine exposure. Brain reward function was assessed daily throughout the regimens, using the intracranial self-stimulation procedure, and after a subsequent acute methamphetamine challenge.Results: Both methamphetamine regimens induced withdrawal-related decreases in reward function. TAT expression substantially, but not significantly increased the withdrawal associated with exposure to the binge regimen compared to the chronic regimen, but did not alter the response to acute methamphetamine challenge. TAT expression also led to persistent changes in adenosine 2B receptor expression in the caudate putamen, regardless of methamphetamine exposure. These results suggest that TAT expression may differentially affect brain reward function, dependent on the pattern of methamphetamine exposure.Conclusion: The subtle effects observed in these studies highlight that longer-term TAT expression, or its induction at earlier stages of methamphetamine exposure, may be more consequential at inducing behavioral and neurochemical effects.
TL;DR: The finding that a high proportion of MSM had knowledge of HIV prevention but still conducted unprotected sex highlights the need for further control measures to change unsafe sexual practices among MSM.
Abstract: OBJECTIVES Ningxia Hui Autonomous Region, an important area for ethnic Hui settlement in Northwest China, is a low HIV prevalence region. However, HIV infection rates among men who have sex with men (MSM) in Ningxia have increased to an alarming level, despite scale-up of control measures in recent years. This study aimed to understand the demographical and sexual behavior dynamics of MSM and to explore the factors associated with HIV infection. METHODS Annual cross-sectional surveys were carried out among MSM during 2011~2017 in Yinchuan, the capital city of Ningxia. Information regarding social demographics, sexual behavior and HIV prevention knowledge was collected. Blood samples were taken for HIV, HCV serological and genetic analysis, and syphilis serological analysis. The dynamic trend was analyzed with trend χ2 test and factors associated with HIV infection were identified by multivariate logistic regression analysis. RESULTS The study found a decreasing trend for mean age of the MSM population over the study period. MSMs with a college education or higher increased significantly, while the proportions that were in a marriage significantly decreased over the study period. The rate of HIV positive among MSM increased during the study period (p<0.05), however, the rate of recently diagnosed infections decreased from 2012 (p<0.05). Overall, a very high proportion (98%) of MSM had basic knowledge of HIV prevention, however, only approximately 40% of them used condoms consistently during anal sex with male partners. Unprotected anal sex was identified as a risk factor associated with HIV infection, as was syphilis infection. Local residency status and MSM who received intervention and detection services were the factors that decreased HIV infection risk. Sequence analysis identified the HIV-1 CRF55_01B subtype from MSM for the first time in Yinchuan. CONCLUSION The reduction of recent HIV diagnoses is an encouraging sign of successful HIV control measures in MSM in Ningxia. The finding that a high proportion of MSM had knowledge of HIV prevention but still conducted unprotected sex highlights the need for further control measures to change unsafe sexual practices among MSM.
TL;DR: There is aLow prevalence of HIV in cancer patients as well as a low prevalence of cancer in HIV patients with the increased coverage of ART, as is evident from data from more developed countries.
Abstract: Author(s): Sinha, Sanjeev; Agarwal, Ashish; Gupta, Kartik; Mandal, Dibyakanti; Jain, Mitul; Detels, Roger; Nandy, Karabi; DeVos, Michelle A; Sharma, SK; Manoharan, N; Julka, PK; Rath, GK; Ambinder, Richard F; Mitsuyasu, Ronald T | Abstract: Background and objectivesPeople living with HIV/AIDS are at an increased risk of developing cancer. The goals of this study were to obtain data on the prevalence of HIV in the cancer population and vice versa at a major tertiary cancer and HIV center in North India.MethodsThis cross-sectional study was conducted over a 3-year period from July 2013 to June 2016, wherein successive HIV positive patients from an anti-retroviral therapy (ART) center were screened for malignancy. Simultaneously, successive cancer patients at the cancer center were screened for HIV. Baseline demographic details, risk factors, and laboratory investigations were obtained for all the patients.ResultsAmong the 999 HIV-positive patients at the ART center, the prevalence of malignancy was 2% (n=20; 95% confidence interval (CI) 1.13, 2.87). Among the 998 patients with a malignancy, the prevalence of HIV infection was 0.9% (n=9; 95% CI 0.31, 1.49). Weight loss, loss of appetite, and fever were the most common symptoms in patients with HIV and cancer. Among 29 patients with HIV and cancer, AIDS-defining cancer was found in 19 patients; non-Hodgkin's lymphoma was the most common malignancy reported (n=13).Interpretation and conclusionThere is a low prevalence of HIV in cancer patients as well as a low prevalence of cancer in HIV patients. AIDS-defining cancers remain much more common than non-AIDS-defining cancers. With the increased coverage of ART, it is expected that non-AIDSdefining cancers will increase, as is evident from data from more developed countries.
TL;DR: Evidence is shown of the comprehensive prevalence of different genotypes, data and characteristics of HIV among IDUs in China, while CRF08-BC was the dominant prevalent strain among ID Units in southwestern China and across the different time frames and regions.
Abstract: BACKGROUND Since 1981, an increasing trend in HIV has been observed for transmission via injection drug users (IDUs), sexual transmission and mother-to-child transmission. The IDUs are blamed for early increases in HIV-positive cases in China. OBJECTIVE HIV genotypes of IDUs were comprehensively analysed to trace the source and relationships of the AIDS epidemic in China. METHODS Relevant databases written in English and Chinese were searched. Overall, 7,149 publications were identified in six databases. After screening 7,104 articles according to the inclusion and exclusion criteria, 45 studies consisting of 2,765 cases were finally identified. A meta-analysis was conducted using R MATLAB software, RevMan and SPSS. Subgroup analyses focused on time frame, region, and location of different genotypes of IDUs in China. RESULTS There were five dominant HIV-1 genotypes among the 2,765 IDU cases. The proportions of CRF07_BC, CRF01_AE, CRF08_BC, subtype B/B', and subtype C were 45.18% (95% CI: 33.55-57.08%), 16.00% (95% CI: 9.39-23.82%), 13.43% (95% CI: 7.32-20.84%), 3.58% (95% CI: 1.52-6.24%), and 0.90% (95% CI: 0.04-2.43%), respectively. HIV genotypes transmitted among IDUs in China are primarily CRF07-BC, followed by CRF01-AE and CRF08-BC. Across the different time frames and regions, CRF07_BC was the most prevalent HIV-1 genotype among IDUs, while CRF08_BC was the most prevalent genotype in the southwest region. CONCLUSION Our study reveals that CRF07-BC was the dominant prevalent strain among IDUs from 1991 to 2015 in China, while CRF08-BC was the dominant prevalent strain among IDUs in southwestern China. This systematic review and meta-analysis shows evidence of the comprehensive prevalence of different genotypes, data and characteristics of HIV among IDUs in China.
TL;DR: It is shown that transmissions are more likely among PWID with high viremia than among people who inject drugs (PWID) with recent HIV infection.
Abstract: Background TRIP (Transmission Reduction Intervention Project) was a network-based, contact tracing approach to locate and link to care, mostly people who inject drugs (PWID) with recent HIV infection. Objective We investigated whether sequences from HIV-infected participants with high viral load cluster together more frequently than what is expected by chance. Methods Paired end reads were generated for 104 samples using Illumina MiSeq next-generation sequencing. Results 63 sequences belonged to previously identified local transmission networks of PWID (LTNs) of an HIV outbreak in Athens, Greece. For two HIV-RNA cut-offs (105 and 106 IU/mL), HIV transmissions were more likely between PWID with similar levels of HIV-RNA (p 106 IU/mL were clustered in 5 pairs. For 4 of these clusters (80%), there was in each one of them at least one sequence from a recently HIVinfected PWID. Conclusion We showed that transmissions are more likely among PWID with high viremia.
TL;DR: While community screening resulted in more MSM knowing their HIV status, reluctance avail of government health facility-based services, or indeed to be tested at all, must be addressed if community screening is to accelerate progress in getting HIV-positive MSM onto treatment.
Abstract: Background Indonesia lags behind its peers with regard to ART coverage of PLHIV. Insufficient HIV testing among MSM and other key affected populations remains a barrier to increasing ART coverage. Objective This report presents the results of the first government-endorsed implementation research study of a community screening approach to increasing the rate of HIV testing among MSM in three cities. Methods All new MSM outreach contacts meeting eligibility criteria during March-June 2017 were included in the study. HIV testing at a government health facility, which is required to qualify for government-supported ART, was advised for all new contacts. Men refusing formal testing were offered an HIV screening test in a community setting using a saliva-based rapid test and advised to get a confirmatory test at a health facility. All outreach contacts and testing activities were recorded on individual client records. Results Of 1,149 eligible MSM, 27% were willing to be referred to receive HIV testing at a health facility, among which 83% were confirmed to have been tested. Of the 838 study subjects refusing health facility testing, 38% accepted community screening. The screening positivity rate was 14.8%. Only 38% of men with reactive screening tests received a confirmatory test at a health facility, along with 8% of those with non-reactive tests. Conclusion While community screening resulted in more MSM knowing their HIV status, reluctance to avail government health facility-based services, or indeed to be tested at all, must be addressed if community screening is to accelerate progress in getting HIV-positive MSM onto treatment.
TL;DR: There is initial evidence that Treg may play a role in preventing mother-to-child transmission of HIV, likely by suppressing immune activation in the fetus and infant, and needs to be substantiated in a larger study.
Abstract: BACKGROUND Mother-to-child transmission of HIV-1 occurs in a minority of HIVinfected mother-infant pairs, even without any interventions. The mechanisms that protect the majority of HIV-exposed infants from infection are unclear. T regulatory cells (Treg) have important immunomodulatory functions, but their role in the fetus as well as in mother-to-child transmission of HIV is under-studied. METHODS We studied available cryopreserved peripheral blood mononuclear cells from HIVexposed infants from the Breastfeeding, Antiretrovirals and Nutrition (BAN) Study cohort in Malawi: 64 infants were HIV-uninfected and 28 infants were HIV-infected at birth. We quantified the frequency of Treg cells (CD4+CD25+FoxP3+), and activated CD4+ and CD8+ T cells (CD38+ HLADR+) by flow cytometry at birth, 6 weeks and 6, 9 and 12 months of age. Descriptive statistics were performed to describe the distributions of these lymphocyte markers according to the HIV infection status; and Student's t tests and Wilcoxon-Rank Sum tests were performed to compare HIVinfected and uninfected infants. RESULTS T cell activation increased rapidly in the first 6 weeks of life, more pronounced on CD8+ T cells; a further increase in activation was observed at the time of weaning from breastfeeding at 6 months of age. In contrast, the frequency of Treg was stable over the first 6 weeks of life (median, 0.5%), slightly decreased between 6 weeks and 6 months (median at 6 months, 0.3%) and then slightly increased between 6 months (time of weaning) and 12 months of age (median, 0.45%). HIVinfected infants had significantly higher frequencies of activated T cells than uninfected infants (P < 0.01). At the time of birth, HIV-exposed uninfected infants had higher levels of Treg, compared to infants infected in utero, even though this did not reach statistical significance in this small sample size (P = 0.08). CONCLUSION This study provides initial evidence that Treg may play a role in preventing mother-tochild transmission of HIV, likely by suppressing immune activation in the fetus and infant, and needs to be substantiated in a larger study. Better characterization of the role of Treg in fetal and neonatal immunity may provide a valuable complementary approach to achieve eradication of mother-to-child transmission of HIV.
TL;DR: The results highlighted the emergence of CRF07_BC epidemic in local MSM community, public health interventions targeting the community should be further enhanced to tackle the epidemic.
Abstract: Background Over the past years, an increasing trend was noticed for non-B and non- CRF01_AE HIV-1 strains prevalence in Hong Kong. Objective In this study, we aimed at using the available HIV-1 pol sequences collected from 1994 to 2013 through our local antiretroviral resistance surveillance program to investigate the molecular epidemiology and evolution of HIV-1 minority subtypes in Hong Kong. We also aimed at investigating their potential association and impact of those transmission risk groups. Methods A total of 2,315 HIV-1 partial pol sequences were included. HIV-1 genotypes were determined by REGA Genotyping Tool and phylogenetic analysis with reference sequences. The viral evolutionary rates and time of the most common ancestor (tMRCA) were estimated by Bayesian Markov Chain Monte Carlo (MCMC) interference. Results Apart from the two prevalent HIV-1 genotypes in Hong Kong (subtype B,41.6%, CRF01_AE,40.5%), phylogenetic analysis revealed a broad viral diversity including CRF07_BC(5.1%), subtype C(4.5%), CRF02_AG(1.1%), CRF08_BC(0.8%), subtype A1(0.8%), subtype G(0.4%), subtype D(0.4%), CRF06_cpx(0.4%), subtype F(0.1%), CRF12_BF(0·04%) and other recombinants(4.5%). The top five minority subtypes were further analyzed which demonstrated distinct epidemiological and phylogenetic patterns. Over 70% of subtypes A1, C and CRF02_AG infections were circulated among non-Chinese Asians or African community in Hong Kong and were mainly transmitted between heterosexual regular partners. Instead, over 90% of CRF07_BC and CRF08_BC patients were Chinese. An epidemic cluster was identified in CRF07_BC and estimated to expand from 2002 onwards based on skyline plot and molecular clock analysis. Conclusion Our results highlighted the emergence of CRF07_BC epidemic in local MSM community, public health interventions targeting the community should be further enhanced to tackle the epidemic.
TL;DR: The results show that the new defined sets achieved a higher percentage of effectiveness to predict the CD4+ value cells, which represents a useful tool that can be proposed as a substitute for clinical values obtained by the flow cytometry.
Abstract: BACKGROUND Previous studies have developed methodologies for predicting the number of CD4+ cells from the total leukocyte and lymphocytes count based on mathematical methodologies, obtaining percentages of effectiveness prediction higher than 90% with a value of less than 5000 leukocytes. OBJECTIVE To improve the methodology probabilities prediction in 5000-9000 leukocytes ranges. METHOD from sets A, B, C and D defined in a previous study, and based on CD4+ prediction established on the total number of leukocytes and lymphocytes, induction was performed using data from 10 patients with HIV, redefining the sets A and C that describe the lymphocytes behavior relative to leukocytes. Subsequently, we evaluated with previous research prediction probabilities parameters from a sample of 100 patients, calculating the belonging probability to each sample and organized in predetermined ranges leukocytes, of each of the sets defined, their unions and intersections. Then the same procedure was performed with the new sets and the probability values obtained with the refined method were compared with respect to previously defined, by measures of sensitivity (SENS) and Negative Predictive Value (NPV) for each range. RESULTS probabilities with values greater than 0.83 were found in five of the nine ranges inside the new sets. The probability for the set A∪C increased from 0.06 to 0.18 which means increases between 0.06 and 0.09 for the intersection (A∪C) ∩ (B∪D), making evident the prediction improvement with new sets defined. CONCLUSION The results show that the new defined sets achieved a higher percentage of effectiveness to predict the CD4+ value cells, which represents a useful tool that can be proposed as a substitute for clinical values obtained by the flow cytometry.
TL;DR: The relatively common nature of antibodies targeting these epitopes, the disparate in vitro results, and lack of reported clinical failures ascribed to such antibodies leads to conclude that antibody interference of T20 is likely not clinically relevant.
Abstract: BACKGROUND During HIV infection, fusion of the viral and cellular membranes is dependent on folding of the gp41 trimer into a six-helix bundle. Fusion inhibitors, such as the antiretroviral Enfuvirtide (T20), interfere with the formation of the gp41 six-helix bundle. Recent in vitro studies reveal that the gp41 immunodominant region one targeting antibody 3D6 can block T20 interference, but the clinical and pathophysiologic significance of this finding is unclear. OBJECTIVE/METHOD We have previously characterized a number of antibodies that target conformational epitopes on gp41and herein characterized their ability to interfere with T20 in multiple assays and assess their prevalence in HIV infected subjects. RESULTS The T20 interference by antibody 3D6 was confirmed in a CHO-HXB2 envelope/ HeLaT4+ cell culture assay. Antibodies that target an immunodominant region one epitope, as well as a gp41 discontinuous epitope, also interfered in this assay, however, not all antibodies that targeted these epitopes showed T20 interference. This response was not due to the direct binding of T20 by the antibodies and could not be replicated utilizing TZM-bl and HL2/3 cells. Notably, serum competition studies on a panel of HIV subjects demonstrate that these conformational targeting antibodies are common in the HIV population. CONCLUSION The relatively common nature of antibodies targeting these epitopes, the disparate in vitro results, and lack of reported clinical failures ascribed to such antibodies leads us to conclude that antibody interference of T20 is likely not clinically relevant. However, this warrants continued consideration with the advancement of other fusion inhibitors.