Human Immunodeficiency Virus Strains Research Articles

429. Antibody Delivery by Genetically Engineered Human Hematopoietic Stem Cells to Fight HIV

The fight against HIV (Human Immunodeficiency Virus) has made considerable progress following antiretroviral therapy development. However, a cure has not been achieved yet due to the existence of replication-competent latent viral reservoirs in sanctuaries such as the Gut-Associated Lymphoid Tissue, lymph nodes or central nervous system. The elimination of these reservoirs appears as a key to eradicate HIV, and developing innovative delivery methods will be critical to reach this goal. Hematopoietic stem cells (HSCs) and derived lineages have been shown to migrate to these sanctuaries and represent a powerful way of delivering therapeutic molecules to target HIV. The recent identification of potent broadly neutralizing antibodies (bNAbs) directed against the Envelope of HIV holds new prospects. In addition to neutralizing various strains of HIV, a few reports have shown the ability of these antibodies to target HIV originating from the latent reservoirs. Recent efforts have focused on bNAbs delivery, but their in vivo half-life remains limited. Delivery by HSCs would provide a durable alternative. Based on these observations, we are genetically modifying CD34+ hematopoietic stem and progenitor cells (HSPCs) to give them the ability to express and secrete potent bNAbs targeting both circulating viral particles and latent viral reservoirs. To this end, cell lines or human HSPCs were transduced by lentiviral constructs encoding selected bNAbs and assessed for their ability to secrete functional antibodies. In vitro, 293T cells were able to release the bNAbs of interest in the supernatants at 4 and 7 days post-transduction. The secreted antibodies were also detected in modified human HSPCs supernatants starting at 9 days and for up to 21 days post-transduction. To assess the antibodies protective effect against HIV in vivo, we have utilized the NOD-SCID-gamma (NSG) mouse model. A single infusion of genetically modified HSPCs in this model allows for immune cell development and subsequent HIV challenge. Circulating human cells are detected in the peripheral blood as early as 8 weeks post-engraftment. Mice have now been challenged with HIV at 12 weeks and the infection is being tracked using quantitative PCR. This model will allow us to determine the ability of genetically modified HSPCs to secrete these bNAbs in vivo and prevent HIV infection as well as to track antibodies delivery to isolated sanctuaries such as the brain. The long-term secretion potency of these modified HSPCs and derived lineages will also be investigated. Here we show the development of an alternative delivery method for antibodies by genetically modified HSPCs. The ability of HSPCs to differentiate into multiple hematopoietic lineages and thus to cross physiological and anatomical barriers represents a valuable asset to target HIV latent viral reservoirs. Another advantage provided by the use of HSPCs is their long-term persistence that should support a long-term secretion and thus treatment. Future development will focus on controlling antibody expression. Importantly, this strategy could be applied to a broad variety of diseases for which antibodies have been shown to be efficient in patients, but require multiple injections for sustainable efficiency.

Cluster of HIV Infections Attributed to Unsafe Injection Practices--Cambodia, December 1, 2014-February 28, 2015.

In December 2014, local health authorities in Battambang province in northwest Cambodia reported 30 cases of human immunodeficiency virus (HIV) infection in a rural commune (district subdivision) where only four cases had been reported during the preceding year. The majority of cases occurred in residents of Roka commune. The Cambodian National Center for HIV/AIDS (acquired immunodeficiency syndrome), Dermatology and Sexually Transmitted Diseases (NCHADS) investigated the outbreak in collaboration with the University of Health Sciences in Phnom Penh and members of the Roka Cluster Investigation Team. By February 28, 2015, NCHADS had confirmed 242 cases of HIV infection among the 8,893 commune residents, an infection rate of 2.7%. Molecular investigation of the HIV strains present in this outbreak indicated that the majority of cases were linked to a single HIV strain that spread quickly within this community. An NCHADS case-control study identified medical injections and infusions as the most likely modes of transmission. In response to this outbreak, the Government of Cambodia has taken measures to encourage safe injection practices by licensed medical professionals, ban unlicensed medical practitioners, increase local capacity for HIV testing and counseling, and expand access to HIV treatment in Battambang province. Measures to reduce the demand for unnecessary medical injections and the provision of unsafe injections are needed. Estimates of national HIV incidence and prevalence might need to be adjusted to account for unsafe injection as a risk exposure.

Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection.

During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies.

HIV coreceptor tropism among patients with newly diagnosed infection

Introduction: Coreceptor tropism is the ability of human immunodeficiency virus (HIV) to use CCR5 or CXCR4 coreceptor to enter the host cell. Tropism depends on the structure of the surface glycoprotein, involved in binding molecules to receptor and coreceptor. Viruses that CCR5use are named R5, viruses that CXCR4 use are X4-tropic, and dual/mixed (DM) viruses use either of the two. During early stages of HIV infection,R5 strains are usually present and with the progression of HIV disease, frequency of X4 occurs. Aim: The aim of the study was to analyze the coreceptor tropism in newly diagnosed HIV infected patients. Material and methods: The study group included 26 patients with newly diagnosed HIV infection, in the hospital care from 2010 to 2012 at the Clinic for Infectious and Tropical diseases of the Clinical Center of Serbia. Upon RNA isolation from plasma, PCR amplification and DNA sequencing of the V3 loop of the env gene were performed. The sequences were used for prediction of the coreceptor tropism, using the Geno2pheno bioinformatics algorithms. Results: R5 and X4 tropism were detected in 21/26 (81%) and 5/26 (19%) patients, respectively. Five out of twenty-six patients (19.2%) were in the C3 clinical stadium of the disease, and all of them were infected with R5-tropic virus. Fourteen out of twenty-five patients (56%) were late presenters of HIV infection, where 12 (86%) of them were infected with R5-tropic virus. Conclusion: Our results imply that the majority of HIV strains in patients, with newly diagnosed infection in Serbia, are characterized by R5 tropism. However, the prevalence of X4 strains is not negligible, indicating late presentation of newly diagnosed patients, but also possibly implying increased virulence of the circulating strains. Considering that CCR5 antagonists would not be effective in 19% of studied patients, the prediction of coreceptor tropism is undoubtedly very important.

Analysis of Immunological, Viral, Genetic, and Environmental Factors That Might Be Associated with Decreased Susceptibility to HIV Infection in Serodiscordant Couples in Florianópolis, Southern Brazil.

Individuals who have been exposed to human immunodeficiency virus (HIV) and have not been infected might possess natural resistance mechanisms. An understanding of the sociodemographic and immunological conditions that influence resistance to HIV is a challenge, and very little is known about the role of intrinsic antiviral factors that restrict HIV infection. The aim of this study was to analyze potential factors responsible for resistance to HIV infection in serodiscordant couples by comparing HIV-exposed seronegative individuals (HESN) to HIV-seropositive individuals treated with antiretroviral therapy (HIV-ART) along with healthy controls (HC). The results revealed one HLA-B*27 and two HLA-B*57 individuals among the HESN; a CCR5Δ32 heterozygous deletion was observed in one serodiscordant couple, while the homozygous genotype for this variant was not observed. There were no differences in the basal mRNA expression of APOBEC3G, CFLAR, TRIM5α, LEDGF/p75, BST-2, or SAMHD1 in CD4(+) T lymphocyte- and monocyte-enriched populations among the three groups, and lower HBD-3 concentrations were observed in saliva from HIV-ART compared to HESN and HC. The most prevalent HIV-1 subtype was C or C-containing recombinant forms. Six HIV-ART individuals and one HIV-ART individual were infected with the R5 HIV and X4 HIV strains, respectively. The ability to control infection or delay disease progression is probably defined by a balance between viral and host factors, and further evaluation should be performed in larger cohorts. Our data suggest that susceptibility to HIV infection varies among individuals and strengthens the multifactorial characteristics underlying the resistance mechanisms in HIV.

The phylogenetic evolution and genetic variations of gag gene among the prevalent human immunodeficiency virus-1 strains in Guangxi region

Objective To study the phylogenetic evolution and genetic variations of gag gene among the prevalent human immunodeficiency virus (HIV)-1 strains in Guangxi Zhuang Autonomous Region. Methods Plasma samples of 158 HIV-1 infected patients in Guangxi area were collected during October 2011 to March 2012. The gag gene fragments of HIV-1 were amplified by reverse transcription/nested-polymerase chain reaction and then sequenced. MEGA 5.03 was utilized to construct phylogenetic tree and to calculate the genetic distances and selection pressures (globle ω) of gag gene and its coding regions. The comparisons between two groups were tested by Student's t test, and the comparisons of multiple groups were tested by one-way ANOVA. Results A total of 140 amplification products of gag gene were obtained from 158 samples. Four subtypes of HIV-1 were found, including CRF01_AE (80, 57.1%), CRF08_BC (46, 32.9%), CRF07_BC (10, 7.1%), and subtype B (B') (4, 2.9%). The genetic distances of gag gene of the above subtypes were 0.036±0.001, 0.031±0.002, 0.043±0.003 and 0.102±0.006, respectively, with statistical significance (F=220.62, P<0.01). The p17 and p24 coding regions suffered negative selection pressure (globle ω<1). Neither the globle ω in p17 region nor that in p24 region had significant differences among different subtypes (F=0.761, P=0.469 and F=0.037, P=0.964, respectively). Conclusion CRF01_AE is the major subtypes of HIV-1 in Guangxi Zhuang Autonomous Region. The coding regions of gag gene are relatively conserved during evolution. Changes of HIV-1 prevalence, however, may affect the genetic variation of gag gene, which should be continuously monitored. Key words: HIV-1; Genes, gag; Variation (Genetics)

Antibodies elicited by yeast glycoproteins recognize HIV-1 virions and potently neutralize virions with high mannose N-glycans

The glycan shield on the human immunodeficiency virus 1 (HIV-1) envelope (Env) glycoprotein has drawn attention as a target for HIV-1 vaccine design given that an increasing number of potent and broadly neutralizing antibodies (bNAbs) recognize epitopes entirely or partially comprised of high mannose type N-linked glycans. In an attempt to generate immunogens that target the glycan shield of HIV-1, we previously engineered a triple mutant (TM) strain of Saccharomyces cerevisiae that results in exclusive presentation of high mannose type N-glycans, and identified five TM yeast glycoproteins that support strong binding of 2G12, a bNAb that targets a cluster of high mannose glycans on the gp120 subunit of Env. Here, we further analyzed the antigenicity and immunogenicity of these proteins in inducing anti-HIV responses. Our study demonstrated that the 2G12-reactive TM yeast glycoproteins efficiently bound to recently identified bNAbs including PGT125-130 and PGT135 that recognize high mannose glycan-dependent epitopes. Immunization of rabbits with a single TM yeast glycoprotein (Gp38 or Pst1), when conjugated to a promiscuous T-cell epitope peptide and coadministered with a Toll-like receptor 2 agonist, induced glycan-specific HIV-1 Env cross-reactive antibodies. The immune sera bound to both synthetic mannose oligosaccharides and gp120 proteins from a broad range of HIV-1 strains. The purified antibodies recognized and captured virions that contain both complex- and high mannose-type of N-glycans, and potently neutralized virions from different HIV-1 clades but only when the virions were enforced to retain high mannose N-glycans. This study provides insights into the elicitation of anti-carbohydrate, HIV-1 Env-cross reactive antibodies with a heterologous glycoprotein and may have applications in the design and administration of immunogens that target the viral glycan shield for development of an effective HIV-1 vaccine.

Using Hierarchical Virtual Screening To Combat Drug Resistance of the HIV-1 Protease.

Human immunodeficiency virus (HIV) protease inhibitors (PIs) are important components of highly active anti-retroviral therapy (HAART) that block the catalytic site of HIV protease, thus preventing maturation of the HIV virion. However, with two decades of PI prescriptions in clinical practice, drug-resistant HIV mutants have now been found for all of the PI drugs. Therefore, the continuous development of new PI drugs is crucial both to combat the existing drug-resistant HIV strains and to provide treatments for future patients. Here we purpose an HIV PI drug design strategy to select candidate PIs with binding energy distributions dominated by interactions with conserved protease residues in both wild-type and various drug-resistant mutants. On the basis of this strategy, we have constructed a virtual screening pipeline including combinatorial library construction, combinatorial docking, MM/GBSA-based rescoring, and reranking on the basis of the binding energy distribution. We have tested our strategy on lopinavir by modifying its two functional groups. From an initial 751 689 candidate molecules, 18 candidate inhibitors were selected using the pipeline for experimental validation. IC50 measurements and drug resistance predictions successfully identified two ligands with both HIV protease inhibitor activity and an improved drug resistance profile on 2382 HIV mutants. This study provides a proof of concept for the integration of MM/GBSA energy analysis and drug resistance information at the stage of virtual screening and sheds light on future HIV drug design and the use of virtual screening to combat drug resistance.

Human Rhinovirus Presenting 4E10 Epitope of HIV-1 MPER Elicits Neutralizing Antibodies in Human ICAM-1 Transgenic Mice.

Attempts at eliciting neutralizing antibodies against human immunodeficiency virus (HIV)-1 have generally failed. Computationally designed epitope-scaffold platforms allow transplantation of structural epitopes to scaffold proteins. Human rhinovirus (HRV) allows such engrafting of HIV-1 epitopes on the surface scaffold proteins. However, since HRV infects only humans and great apes, the efficacy of chimeric HRV-based live viral vaccines is difficult to assess in animal models. Here, we used human ICAM-1 transgenic (hICAM-1 Tg) mice that support productive HRV infection to assess the efficacy of chimeric HRV expressing the HIV-1 membrane proximal external region (MPER) epitope, 4E10. Intranasal immunization with chimeric HRV in transgenic mice effectively induced antibodies that recognized 4E10 peptide as well as HIV-1 Env trimer. Importantly, the immunized mouse sera were able to neutralize HIV strains including those belonging to clades B and C. Moreover, intranasal immunization could bypass pre-existing immunity to HRV. Thus, chimeric HRV appears to provide a viable vaccine vehicle for HIV-1 immunization in humans.

Development of maraviroc, a CCR5 antagonist for treatment of HIV, using a novel tropism assay.

Assays to identify infectious organisms are critical for diagnosis and enabling the development of therapeutic agents. The demonstration that individuals with a 32-bp deletion within the CCR5 locus were resistant to human immunodeficiency virus (HIV) infection, while those heterozygous for the mutation progressed more slowly, led to the discovery of maraviroc (MVC), a CCR5 antagonist. As MVC is only active against CCR5-tropic strains of HIV, it was critical to develop a diagnostic assay to identify appropriate patients. Trofile™, a novel phenotypic tropism assay, was used to identify patients with CCR5-tropic virus for the MVC development program. Results of these clinical studies demonstrated that the assay correctly identified patients likely to respond to MVC. Over time, the performance characteristics of the phenotypic assay were enhanced, necessitating retesting of study samples. Genotypic tropism tests that have the potential to allow for local use and more rapid turnaround times are also being developed.

A Plant-Derived Multi-HIV Antigen Induces Broad Immune Responses in Orally Immunized Mice.

Multi-HIV, a multiepitopic protein derived from both gp120 and gp41 envelope proteins of the human immunodeficiency virus (HIV), has been proposed as a vaccine prototype capable of inducing broad immune responses, as it carries various B and T cell epitopes from several HIV strains. In this study, the immunogenic properties of a Multi-HIV expressed in tobacco chloroplasts are evaluated in test mice. BALB/c mice orally immunized with tobacco-derived Multi-HIV have elicited antibody responses, including both the V3 loop of gp120 and the ELDKWA epitope of gp41. Based on splenocyte proliferation assays, stimulation with epitopes of the C4, V3 domain of gp120, and the ELDKWA domain of gp41 elicits positive cellular responses. Furthermore, specific interferon gamma production is observed in both CD4+ and CD8+ T cells stimulated with HIV peptides. These results demonstrate that plant-derived Multi-HIV induces T helper-specific responses. Altogether, these findings illustrate the immunogenic potential of plant-derived Multi-HIV in an oral immunization scheme. The potential of this low-cost immunization approach and its implications on HIV/AIDS vaccine development are discussed.

Isolation and biological characterization of human immunodeficiency virus type 1 from Cubans asymptomatic patients

Isolation and biological characterization of human immunodeficiency virus type 1 from Cubans asymptomatic patients

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

New World Health Organization guidelines recommend the initiation of antiretroviral treatment (ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm(3). Substantial reduction of human immunodeficiency virus (HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa (MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it's at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients' CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners - either female sex workers or women in monogamous relationships with high-risk men - are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by cost-effective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region.

Establishment and optimization of a high throughput phenotypic test for the detection of drug resist-ance in human immunodeficiency virus（HIV）strains

Objective To establish a high throughput phenotypic test for the detection of drug resistance in human immunodeficiency virus（HIV）strains. Methods The gene encoding luciferase was inactivated through restriction enzyme digestion and ligation. LacZ gene was used to replace the genes encoding original protease and reverse transcriptase. pol genes were amplified from pSG3△env plasmid and cloned into a new backbone plasmid through infusion. The factors that might affect the results of the test were optimized. Results The parental backbone plasmid pNL4-3. Lac was constructed,of which the gene encoding luciferase was inactivated and bearing the LacZ gene instead of genes encoding protease and reverse transcriptase. Several influential factors including cell numbers（10 000 / well）,virus inoculation（200 TCID50 /well）and the concentration of DEAE-dextran（15 μg/ ml）were optimized. The reproducibility of this test was confirmed by testing 12 anti-HIV drugs against 2 pseudovirus strains 8 times,presenting the coefficient of variations（CVs）from 4. 32% to 28. 46% . Six types of pseudovirus were constructed and tested against the 12 anti-HIV drugs,the results of which were compared with those by using the pSG3△env-based pseudovirus test. The results of the two tests presented good consistency. Conclusion The high throughput phenotypic test based on pNL4-3. Lac plasmid,combining the advantages of pSG3△env and pNL4-3 systems, could be used to analyze the drug resistance patterns of HIV-1 infectors and screen new drugs for antiretroviral therapy in a rapid and effective way. Key words: Human immunodeficiency virus; Drug resistance; Phenotypic test

Selective interaction of heparin with the variable region 3 within surface glycoprotein of laboratory-adapted feline immunodeficiency virus.

Heparan sulfate proteoglycans (HSPG) can act as binding receptors for certain laboratory-adapted (TCA) strains of feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV). Heparin, a soluble heparin sulfate (HS), can inhibit TCA HIV and FIV entry mediated by HSPG interaction in vitro. In the present study, we further determined the selective interaction of heparin with the V3 loop of TCA of FIV. Our current results indicate that heparin selectively inhibits infection by TCA strains, but not for field isolates (FS). Heparin also specifically interferes with TCA surface glycoprotein (SU) binding to CXCR4, by interactions with HSPG binding sites on the V3 loop of the FIV envelope protein. Peptides representing either the N- or C-terminal side of the V3 loop and containing HSPG binding sites were able to compete away the heparin block of TCA SU binding to CXCR4. Heparin does not interfere with the interaction of SU with anti-V3 antibodies that target the CXCR4 binding region or with the interaction between FS FIV and anti-V3 antibodies since FS SU has no HSPG binding sites within the HSPG binding region. Our data show that heparin blocks TCA FIV infection or entry not only through its competition of HSPG on the cell surface interaction with SU, but also by its interference with CXCR4 binding to SU. These studies aid in the design and development of heparin derivatives or analogues that can inhibit steps in virus infection and are informative regarding the HSPG/SU interaction.

An investigation into the comparison of three human immunodeficiency virus (HIV) drug resistance interpretation algorithms

Human immunodeficiency virus (HIV) drug resistance is caused by mutations in the patient’s human immunodeficiency virus genome that renders antiretroviral (ARV) drugs less effective. Drug resistance not only results in the patient being more vulnerable to opportunistic infections, but also may increase the spread of resistant strains of HIV. Interpretation computer algorithms may be used to determine which ARV drug(s) the patient are resistant to, by analyzing the mutations that occurred in the patient’s HIV genome, instead of using expensive time consuming phenotypic laboratory tests. There are many different interpretation algorithms, but they often provide different resistance measures, even if applied to the same resistance profile. The aim of this study was to compare the latest versions of three HIV drug resistance interpretation algorithms in order to determine the extent of discrepancies between them. 2926 protease and 1981 reverse transcriptase subtype B sequences where obtained from the Stanford HIV-db genotype-phenotype correlation database. These sequences were pre-processed and the latest rules of the ANRS, HIV-db and REGA algorithms applied to them. The results were then compared with each other. These results indicate that although the accuracy of REGA, ANRS and HIV-db are similar, a deeper analysis of the results indicates that the interpretation algorithms are different. There need to be a mechanism of providing a single interpretation for a resistance profile of a genome. This may be created by collating the strengths of each of the interpretation algorithms. Key words: Bioinformatics, human immunodeficiency virus (HIV), REGA, Agence Nationale de Recherches sur le SIDA (ANRS), HIV-db, genotype, interpretation algorithms.

Non-B HIV-1 subtypes in sub-Saharan Africa: impact of subtype on protease inhibitor efficacy.

In 2012, 25 million people [71% of global human immunodeficiency virus (HIV) infection] were estimated to be living with HIV in sub-Saharan Africa. Of these, approximately 1.6 million were new infections and 1.2 million deaths occurred. South Africa alone accounted for 31% of HIV/acquired immunodeficiency syndrome (AIDS) deaths in sub-Saharan Africa. This disturbing statistic indicates that South Africa remains the epicenter of the HIV/AIDS pandemic, compounded by the fact that only 36% of HIV-positive patients in South Africa have access to antiretroviral (ARV) treatment. Drug resistance mutations have emerged, and current ARVs show reduced efficacy against non-B subtypes. In addition, several recent studies have shown an increased prevalence of non-B African HIV strains in the Americas and Europe. Therefore, the use of ARVs in a non-B HIV-1 subtype context requires further investigation. HIV-1 subtype C protease, found largely in sub-Saharan Africa, has been under-investigated when compared with the subtype B protease, which predominates in North America and Europe. This review, therefore, focuses on HIV-1 proteases from B and C subtypes.

HIV-1 and GBV-C co-infection in Venezuela.

Co-infection with GB virus C (GBV-C) in patients infected with human immunodeficiency virus 1 (HIV-1) has been associated with prolonged survival. The aim of this study was to evaluate the prevalence of GBV-C infection among HIV-1-infected patients in Venezuela, and to determine the effects of the co-infection on the levels of relevant cytokines. Plasma samples were collected from 270 HIV-1-seronegative and 255 HIV-1-seropositive individuals. GBV-C infection was determined by RT-PCR of the NS5 region and genotyped by sequence analysis of the 5´UTR region. HIV-1 strains were characterized by sequence analysis of pol, vif, env, and nef genes. Selected cytokines were evaluated by ELISA. Ninety-seven of 525 (18.5%) plasma samples tested positive for GBV-C RNA. A significantly higher prevalence of GBV-C was found among HIV-1 patients compared to HIV-1-seronegative individuals (67/255, 26% versus 30/270, 11%; p < 0.001). Statistical difference was observed in the viral load between HIV-1+GBV-C+ and HIV-1+GBV-C- (p = 0.014), although no differences in CD4+ cell counts were found between both groups. TNFα concentration was higher in HIV-1+GBV-C- than in HIV-1+GBV-C+ patients (25.9 pg/mL versus 17.3 pg/mL; p = 0.02); RANTES expression levels were more variable in GBV-C co-infected patients and more frequently elevated in HIV-1 mono-infected patients compared to patients co-infected with GBV-C. The previously observed beneficial effect of co-infection with HIV-1 and GBV-C on disease progression is complex and might be due in part to a change in the cytokine environment. More studies are required to understand the interaction between both viruses.

A review on human immunodeficiency virus (HIV) strain candidate vaccine development: Prospect and challenges

Human immunodeficiency virus (HIV) has one of the highest incidence and mortality rates of any infectious disease, with more than 33 million people infected worldwide. Specifically, HIV causes the destruction of helper T cells, ultimately resulting in the suppression of the immune system and leaving its human host susceptible to countless of other pathogenic agents. The development of an effective HIV vaccine has continued for more than 20 years. But the use of preventative vaccines using traditional vaccine technologies, which have proven successful for other diseases, has thus far failed with HIV. One vaccine, AIDSVAX, was the first HIV vaccine to reach a phase III efficacy trial, but has not yet been shown to eradicate HIV. Hope now lies in the development of therapeutic vaccines using novel technologies. One such vaccine is ALVAC-HIV, which when used in conjunction with other vaccines (AIDSVAX or Lipo-6T with IL-2 injections) has shown a great deal of promise in clinical trials suppressing viral replication and improving the immune system. Other therapeutic vaccines, such as Ad5, however, have been unsuccessful. While many believed that developing an effective HIV vaccine is impossible, efforts continue into researching its structure, transmission, immune system suppression, genetic variability, and immune system evasion. As long as research continues, hope remains that someday an effective vaccine will be developed. Key words: Vaccines, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), recombinant, lymphocytes.

HIV transmission at a Saudi Arabia hemodialysis unit.

Hemodialysis is associated with increased risk of healthcare-associated infections but considered a low-risk setting for human immunodeficiency virus (HIV) transmission. We investigated 3 hemodialysis unit (HDU) patients with new HIV infections to determine whether transmission was hemodialysis-associated and to correct factors that contributed to transmission. Each patient was evaluated for HIV risk factors. Blood samples were tested to determine relatedness of HIV strains. Clinical data (gathered over 18 months) was reviewed to identify seroconversions at 12 HDUs. Infection prevention and control practices were evaluated at 14 HDUs. No other HIV seroconversions were identified during the study. HIV gag, pol, and env gene sequences were consistent with a clonal relationship. HIV and hepatitis C virus prevalence rates at one HDU 1 (5.7% and 6.5%, respectively) were higher than for 11 other HDUs (0% and 0.15%, respectively). Sequencing supports either patient-to-patient or common-source transmission. Infections occurred despite Saudi Arabia's low HIV prevalence and national dialysis policies that emphasize stringent infection prevention and control practices.