Current HIV Research - Volume 15, Issue 6, 2017

Background: Despite great improvements in prevention over the last years, much has to be done to reduce new human immunodeficiency virus (HIV) infections. Substantial evidence shows that the six-month period of recent HIV infection contributes disproportionately to HIV transmission. Objective: This study aims to investigate knowledge, normative beliefs, and attitudes of people who inject drugs (PWID) regarding recent HIV infection. Methods: People who inject drugs in Athens, Greece were recruited in the fifth round of a respondent- driven sampling program (ARISTOTLE). The participants were tested for HIV and answered a structured questionnaire, which also included items on knowledge, normative beliefs, and attitudes regarding recent infection to address needs of the social network-based Transmission Reduction Intervention Project. The multivariable analyses included logistic regression models, which produced odds ratios (OR) and 95% confidence intervals (CI). Results: In total, 1,407 people (mean age: 36.3 ± 7.9 years old; males: 81.9%) took part in the fifth round of ARISTOTLE. Of these, 61.5% knew that HIV-infected people who are not on treatment are more likely to transmit HIV during the first six months of their infection and 58.4% reported that people in their network would react positively towards a recently HIV-infected person. People who inject drugs who were knowledgeable of recent HIV infection were more likely to disagree with statements such as that one should avoid all contact with a person recently infected by HIV (adjusted OR: 1.510, 95% CI: 1.090, 2.091) or more likely to agree with statements such as that an HIV+ person is much less likely to transmit HIV when h/she is on combination antiretroviral treatment (adjusted OR: 2.083, 95% CI: 1.231, 3.523). Conclusion: A considerable proportion of PWID in Athens, Greece, were aware of the high HIV transmission risk of recent HIV infection, although improvement is needed for some population segments. People who inject drugs who were knowledgeable of the role of recent HIV infection were more likely to have normative beliefs and attitudes that favor behaviors that could help rather than harm or stigmatize people who have recently been infected with HIV. Interventions that are based on the role of recent HIV infection in HIV transmission could be important to HIV prevention.

Background: New diagnoses of HIV-1 infection among people who inject drugs (PWID) increased significantly during 2011 in Athens. Objective: Our aim was to investigate the patterns of HIV epidemic spread among PWID and to estimate the transmission dynamics for the major local transmission networks (LTNs). Methods: We analyzed sequences from 2,274 HIV-infected subjects sampled in Greece during 01/01/2011-31/10/2014. Of specimens in our sample, 874 sequences were isolated from HIV-infected PWID. Phylodynamic analysis was performed using birth-death serial skyline models. Results: Phylogenetic analysis revealed that the majority of sequences from PWID (N=746, 85.4%) fell within four LTNs: CRF14_BG (N=456, 58.3%), CRF35_AD (N=149, 19.1%), subtype B (N=118, 15.1%) and A1 (N=59, 7.5%). In addition to PWID, we also found that sequences from 36 non-PWID belonged to the LTNs corresponding to cross-group transmissions. Based on the estimated plots of the effective reproductive number (Re) over time, subtype A1 and CRF35_AD LTNs showed a sharp increase before and during 2011 (maximum value of Re=3.0 and Re=4.6, respectively). For subtype B and CRF14_BG LTNs, the Re was increasing until the end of 2012 (maximum value of Re=3.2 and Re=3.0, respectively). Conclusion: HIV transmissions within subtype A1 and CRF35_AD LTNs increased sharply during the early stage of the outbreak, in contrast to subtype B and CRF14_BG. A significant reduction in the number of infections was estimated on all transmission networks from the beginning of 2013 onwards. Prevention measures that took place in the Athens metropolitan area at the end of 2012 including also the ARISTOTLE program may explain this decrease.

Background: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk. Methods: Retrospective single-centre study of HIV patients treated with HAART. Results: A total of 417 patients were included. We identified 45 cases of IRIS in 37 patients; an incidence of 13.3 cases over 1000 person-years. In univariate analysis, IRIS development was significantly associated with CDC stage, the presence of an opportunistic infection (OI) at diagnosis, CD4 cell count and viral load at diagnosis and HAART initiation and the use of integrase strand inhibitors (INSTIs). In multivariate analysis, INSTIs use (OR 2.89; 95%CI 1.26-6.64; p=0.012), CD4≤200/mm3 (OR 5.56; 95%CI 2.2-13.98; p<0.001), and the presence of an OI (OR 4.74; 95%CI 2.13-10.23; p=0.012) were independent risk factors. Among INSTI regimens, dolutegravir (OR 4.99 vs. NNRTI; 95%CI 1.11-22.55; p=0.037) and elvitegravir (OR 4.82 vs. NNRTI; 95%CI 1.43-16.19; p=0.011) seem to carry increased risk. Mortality was 18.9% (7/37) for IRIS patients compared to 9.7% (37/380) in the non-IRIS group. Mortality at any given time during follow-up was significantly higher in the IRIS group (HR 3.2; 95%CI 1.39-7.36; p=0.006). Conclusion: The use of INSTIs and especially DTG and EVG is associated with a higher probability for the development of IRIS in the background of late presentation and the presence of OIs. These data highlight the need for further research.

Background: Human immunodeficiency virus type-1 (HIV-1) infection leads to acquired immunodeficiency syndrome (AIDS), a severe viral infection that has claimed approximately 658,507 lives in the US between the years 2010-2014. Antiretroviral (ARV) therapy has proven to inhibit HIV-1, but unlike other viral illness, not cure the infection. Objective: Among various Food and Drug Administration (FDA)-approved ARVs, nucleoside/ nucleotide reverse transcriptase inhibitors (NRTIs) are most effective in limiting HIV-1 infection. This review focuses on NRTIs mechanism of action and metabolism. Methods: A search of PubMed (1982-2016) was performed to capture relevant articles regarding NRTI pharmacology. Results: The current classical NRTIs pharmacology for HIV-1 prevention and treatment are presented. Finally, various novel strategies are proposed to improve the efficacy of NRTIs, which will increase therapeutic efficiency of present-day HIV-1 prevention/treatment regimen. Conclusion: Use of NRTIs will continue to be critical for successful treatment and prevention of HIV-1.

Although HIV/HCV co-infected individuals were historically considered a “difficult to treat” population in the era of Interferon (IFN)-based anti-HCV treatment, the introduction of directacting antivirals, characterized by excellent efficacy and good safety profile, has widely revolutionized the HCV treatment scenario. Recent real life studies reported excellent sustained virological response rates in HIV/HCV coinfected subjects, thus confirming data obtained in randomized clinical trials. However, certain issues have recently emerged in this population. In fact, high rates of acute HCV infection and reinfections were documented in several studies, particularly in HIV-positive men who have sex with men. Moreover, drug-drug interactions with ART or other co-medications may require careful considerations as well as the management of HIV/HCV co-infected subjects with chronic kidney disease and advanced liver disease in the course of a DAA-based treatment. Hence, we aim to review DAA efficacy studies performed in HIV/HCV co-infected patients in both randomized clinical trials and real-world cohorts. In addition, current challenges and future perspectives are discussed in order to optimize management strategies for HIV/HCV co-infected subjects and their access to care in clinical practice.

Background: Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. Objective: In this study, we used fusion gene of MPER and V3 to product recombinant VLPs and introduced a novel retroviral VLPs harboring high copy of MPER-V3 for HIV-1 vaccine design. Methods: The pEGFP-N1 plasmid harboring MPER-V3 sequence with Vpr linker was constructed. To produce virus-like particles, HEK 293T cells were co-transfected with the recombinant plasmid, pSPAX-2, pMD2-G and pWPXLd plasmids, evaluated by AFM and SEM microscopy and quantified using P24 end-point ELISA assay. Results: Time-course quantification of p24 protein as the characteristics of viral production evidenced for the efficient secretion of virus-like structures (up to 120 ng/ml) to the culture supernatant of transfected cells. Examination of the centrifuge-concentrated VLPs by AFM and SEM microscope, also illustrated particles with spherical morphologies and diameters of around 150 nm that had similar sizes to HIV virions. Conclusion: These data indicated the production of HIV-1 virus-like particles harboring high copy of MPER-V3 that maintained their antigenic structure. These VLPs represented a good implication as a potential vaccine candidate and this guarantees the further investigations towards the assessment of its immunogenicity.

Background: HIV-1+ long-term nonprogressors (LTNPs) maintain natural control of viral infection. This study sought to identify and characterize HIV- LTNPs series case, regarding the presence of possible host factors that may be associated with this status. Methods: We evaluated the plasma levels of IP-10/IL-8 chemokines, HLA-B alleles, and IL28B rs12979860 polymorphism in 24 LTNPs who presented with infection by different clades of HIV-1. Results: IL-8 chemokine was significantly higher in progressors than in LTNPs, but there was no difference between the LTNP subgroups. There was a negative correlation in CD4+ T cell (TC) count and IL-8 dosage, and a positive correlation with CD8+ TC. IP-10 chemokine levels were associated with viremia, and the elite controller (EC) subgroup showed nearly the same level than healthy individuals and progressors with viral load suppressed. Furthermore, the CD4+ TC count, percentage of CD4+ TC, and CD4/CD8 ratio were negatively correlated with IP-10. No association was found in plasma levels of IL-8 and IP-10 chemokines and HIV-1 clades. In the EC/viremic controller subgroup, 80% presented with at least one HLA-B allele previously considered as potentially protective for AIDS progression. No association was observed between the HLA-B alleles and HIV- 1 clades. The IL28B CC genotype was identified in 87.5% of LTNPs. Conclusion: In this LTNP series case we observed different host factors that may be contributing to their nonprogressor status, and the association of these factors with the control of infection progression may be critically important for future therapeutic and prophylactic options in HIV-1 infection.

Background: Total HIV-DNA load in peripheral blood cell (PBMCs) reflects the global viral reservoir that seems not to be affected by antiretroviral treatment. However, some studies reported a different permeability of different drugs in cellular compartments. Objective: To investigate the relation between the amount of total HIV-1 DNA and different treatment strategies. Methods: Total HIV-1 DNA was quantified by real time PCR in PBMCs collected from 161 patients with long-term undetectable HIV-RNA receiving different therapy schedules (3-drug regimens or 2-drug regimen containing Raltegravir as integrase inhibitor). Results: Overall, HIV patients who started therapy with a median pre-ART CD4+ cell count >400 cells/mm3 and HIV viral load of 3 log10 copies/ml, achieved a lower amount of HIV total DNA. No significant correlation was found in DNA size when patients were stratified on the basis of different therapeutic protocols. However, HIV DNA load analysis, when only performed in HIV patients with a median pre-ART CD4+ cell count >200 cells/mm3 and HIV viral load < 3 log10 copies/ml, showed a significative DNA decrease in Raltegravir treated group with respect to the NNRTIs-treated group. Conclusion: The data emphasize that HIV-DNA level represents a predictive factor in long-term suppressive therapy patients. In addition, the diminished reservoir, only observed in patients treated with the NRTI-sparing regimen RAL plus PI/r before immunological and virological derangement, suggests that latest generation drugs, such as integrase inhibitors, might represent an optimal chance in the management of HIV infection.