Current HIV Research - Volume 15, Issue 5, 2017

Background: Although HIV and injury contribute substantially to disease burdens in lowand middle-income countries (LMIC), their intersection is poorly characterized. Objective: This systematic review assessed the prevalence and associated mortality impact of HIVseropositivity among injured patients in LMIC. Methods: A systematic search of PubMed, EMBASE, Global Health, CINAHL, POPLINE and Cochrane databases through August 2016 was performed. Prospective and cross-sectional reports of injured patients from LMIC that evaluated HIV-serostatus were included. Two reviewers identified eligible records (kappa=0.83); quality was assessed using GRADE criteria. HIV-seroprevalence and mortality risks were summarized and pooled estimates were calculated using random-effects models with heterogeneity assessed. Results: Of 472 retrieved records, sixteen met inclusion. All reports were of low or very low quality and derived from sub-Saharan Africa. HIV-serostatus was available for 3,994 patients. Individual report and pooled HIV-seroprevalence estimates were uniformly greater than temporally matched national statistics (range: 4.5-35.0%). Pooled reports from South Africa were three-fold greater than matched national prevalence (32.0%, 95% CI, 28.0-37.0%). Mortality data were available for 1,398 patients. Heterogeneity precluded pooled mortality analysis. Among individual reports, 66.7% demonstrated significantly increased relative risks (RR) of death; none found reduced risk of death among HIV-seropositive patients. Increased mortality risk among HIV-seropositive patients ranged from 1.86 (95% CI, 1.11-3.09) in Malawi to 10.7 (95% CI, 1.32-86.1) in South Africa. Conclusion: The available data indicate that HIV-seropositivity among the injured is high relative to national rates and may increase mortality, suggesting that integrated HIV-injury programming could be beneficial. Given the data limitations, further study of the HIV-injury intersection is crucially needed.

Background: Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of this fact is the IN polymorphism and the associated differences in codon usage, which in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype. Objective: The aim of this work was to assess the prevalence of naturally occurring polymorphisms within the HIV-1 integrase gene, which might influence the susceptibility to INSTIs, among the patients from Russia and former USSR countries, according to HIV-1 subtypes. Method: A study involved 506 HIV-1 IN sequences of INSTI-naive patients from Russia, Ukraine, Armenia, Kyrgyzstan, Kazakhstan, Uzbekistan, Belarus, and Georgia. Among them, 194 sequences were newly obtained in this study and 312 were downloaded from Los-Alamos database. The proviral DNA was sequenced using an in-house PCR protocol designed on the basis of a well-conserved integrase region in order to detect all HIV-1 variants. Results: The phylogenetic analyses based on IN population sequencing found subtype A6 being the most prevalent (259) (51.2%) in the collection studied, followed by subtype G (36) (7.1%), AGrecombinants (148) (29.3%), subtype B (50) (9.9%), and CRF03_AB (5) (1.0%). The major INSTI resistance-associated mutations (DRMs) were found only in two A6 samples. The prevalence of minor/ accessory substitutions depended on HIV-1 variants, while the most notable findings were L74I in subtype A6 (93.1%) and E157Q in subtype B (44.0%). Most of minor DRMs and polymorphic substitutions were concentrated in the central catalytic domain of the IN molecule. Both the DDE triad and HHCC zinc binding motifs were fully conserved. Conclusion: The results of the study suggest a very low risk of initiating INSTI-based therapy in patients with pre-existing polymorphic mutations in Russia and FSU countries. The therapy response in dominating HIV-1 genetic variants might be further studied in the future for a better understanding of their effect on INSTI susceptibility. The INSTI TDR is absent for the moment, but the risk may increase with expanded use of INSTIs, indicating the need for ongoing surveillance.

Introduction: With advances in proteomics, it is essential to investigate the molecularlevel participation of IL27 and gp130 to hinder HIV infection. Their interaction causes cell-cycle arrest in HIV+ cells by activating the receptor-associated JAK signaling and causing apoptosis of cancerous cells. Methodology: The best human wild-type WT_IL27 model was prepared after varied molecular modeling techniques. The vital tyrosine residues in WT_IL27 were identified, mutated and IL27 was re-modeled. Both wild-type and mutant IL27 were docked individually with human gp130 ectodomain complex. Best cluster sized complex was opted and the complexes (WT and MT) were MD (molecular dynamics) simulated. Protein-protein interacting residues, binding patterns, thermodynamic stability, solvent accessibility and many such parameters were evaluated to affirm the stability in the mutant complex. Statistical significances were drawn too. Result and Discussion: With statistical significances also, the mutant type (MT) IL27 was comprehended as the most stable one. Their functionality remained the same. Ionic interactions were the most dominating ones. Exceptionally several Arg residues from MT_IL27 appeared to play a major role, thereby stabilizing the simulated MT_IL27-gp130 complexes. Manifold energy estimations for the complexes, electrostatic potential and increment in %helices and %β-sheets revealed the simulated MT_IL27-gp130 complex to be more stable. In the MT_complex, residues forming 3-ten helices remained constant with major increase in α–helices. This thereby infers the complex as the steadiest and most interactive one. Conclusion: The residual exploration with the detailed structural analysis would aid in the effective drug discovery by targeting the drugs at the interacting sites with the specific binding patterns as analyzed from the study. Conformational stability and other several parameters for thermodynamic stability and accomplishment of strong interaction were also explored. Altogether, this probe provides a limelight towards the mutational alterations in WT IL27, which might allow it to act as a strong peptide inhibitor by shielding HIV entry, more potently.

Background: The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. Objective: To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. Methods: The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values ≥30 ng/mL defined a vitamin D sufficient (VDS) status, and <30 ng/mL defined the presence of hypovitaminosis D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. Results: The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (p<0.0001 and p=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (p<0.0001). HIV-1-infected individuals with HD showed higher hydroperoxide levels than those with a VDS status (p=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D ≥30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). Conclusion: These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways.

Background: The impact of protein intake level leads to considerable alterations of the host essential amino acid profiles in the context of chronic viral infectious process. Amino acids play an important role in the pathogenesis of virus-related infections both as basic substrates for constant protein synthesis and as regulators in many metabolic pathways. The excess or deficiency of these host essential nutritional elements can play a limiting role in the life cycle of some viruses. Objective: Our aim was to determine the changes of hematological parameters and viral load due to the high protein and L-lysine amino acid intake in HIV-infected patients. Methods: Case-control study was performed in the Municipal Center of HIV/AIDS prophylaxis, Surgut, Russian Federation. Results: The obtained data indicate that excess of dietary protein and L-lysine can increase the risk of high HIV replication, subsequent acceleration of immunosuppression and the disease progression. The present survey shows that HIV-infected Khanty indigenous people have the highest levels of plasma L-lysine and HIV-1 RNA and a more pronounced state of immunosuppression in comparison with the total patients' cohort. Conclusion: There was evidence for an association between plasma L-lysine level and viral load. These findings are important for understanding the pathogenic impact of animal protein and Llysine consumption on the HIV-1 RNA levels and must be considered in further research for the development of new approaches in the treatment of HIV infection in era of HAART.

Background: Raltegravir (RAL) is considered one of the better-tolerated antiretroviral medications, due to limited side effects and minimal drug-drug interactions. Matherials and Methods: We retrospectively evaluated 96 HIV+, over 60 years old, experienced patients who had switched from any antiretroviral drug to raltegravir-based nuc-sparing or standard nucleoside-backbone regimens. A control group with patients aged under 60 years old was included. Results: The median age of the patients was 66 years (IQR 10.5) (77 M, 19 F); the median time horizon of follow-up was 4 years (IQR 5). HIV-RNA at baseline was undetectable for more than 6 months in most of the patients. Median CD4+ count was 453 cells/mmc (IQR 379). 49 patients had AIDS history. All the patients were assuming concomitant medications. No adverse effect attributed to the use of raltegravir was reported in the medical records. Only 2 patients presented virological failure, whereas viremic blips were observed in 10 patients. After switching to RAL-containing regimens triglycerides values showed a statistically significant reduction from a median value of 172 (IQR 105.5) mg/dl to 129 mg/dl (IQR 73) (p=0,0001). Switching to a standard regimens was associated with a marked reduction of triglycerides. Cholesterol levels were reduced at the time of follow-up (T2) but no significant modifications were observed when patients which had introduced drugs to treat dislypidemia were removed from the analysis; in contrast, triglycerides reduction was also confirmed in this sub-group. Patients presented higher levels of CD4+ at T2 and reduced platelet count [from 230 300/mmc (SD 123 527) to 197 125/mmc (SD 66 377), p=0,04]. Similar trends were observed in younger patients. Conclusion: RAL-containing regimens are safe and highly effective in the older population. RALtreatment is associated with the reduction of triglycerides and platelets count in the older population.

Background: Relatively little attention has been paid to the significant HIV prevention role that voluntary medical male circumcision (VMMC) can play in populations with moderate levels of HIV prevalence. One such location is Tanah Papua, Indonesia, which in 2013 had a general population having HIV prevalence of 2.3% concentrated among indigenous Papuans (2.9% prevalence), very few of whom are circumcised. This article reports the findings of an implementation research study assessing the acceptability and feasibility of introducing VMMC for HIV prevention. Methods: Following a situational assessment and socialization of targeted groups of men and key stakeholders, a single-arm, open-label, prospective cohort trial using the non-surgical PrePex® device was undertaken in four cities. Study participants were recruited via study-associated socialization events. Data were collected from clients prior to and following device insertion, and at several “check-up” points (2-, 21- and 42-days) using standardized case report forms. A random sample of circumcision clients from one city was surveyed six months’ post-removal to assess the prevalence of compensatory sexual risk behaviours. Results: Demand for circumcision was weak in three of the cities, reflecting insufficient prior socialization and lingering concerns over religious appropriateness and safety issues. Despite no prior experience with PrePex®, the pilot implementation yielded side-effect and adverse event rates that were unremarkable in comparison with sub-Saharan African countries, where PrePex® is widely used. No evidence of increased post-procedure sexual risk-taking was found. Conclusion: The study findings point to both opportunity and significant challenges in introducing VMMC on a large scale in Tanah Papua, Indonesia. Although there were enough promising signs in the qualitative research and in the limited-scale implementation trial undertaken to remain optimistic as to the potential for VMMC to help contain HIV in Tanah Papua, much remains to be done to promote the benefits of VMMC and address lingering concerns as to safety and religious appropriateness. An acceleration of the pace of task-shifting from physicians to nurses will be needed in order for VMMC to be feasible for implementation on a large scale.

Background: Healthcare settings screen broadly for HIV. Public health settings use social network and partner testing (“Transmission Network Targeting (TNT)”) to select high-risk individuals based on their contacts. HIV screening and TNT systems are not integrated, and healthcare settings have not implemented TNT. Objective: The study aimed to evaluate pilot implementation of multi-component, multi-venue TNT in conjunction with HIV screening by a healthcare setting. Methods: Our urban, academic health center implemented a TNT program in collaboration with the local health department for five months during 2011. High-risk or HIV positive patients of the infectious diseases clinic and emergency department HIV screening program were recruited to access social and partner networks via compensated peer-referral, testing of companions present with them, and partner notification services. Contacts became the next-generation index cases in a snowball recruitment strategy. Results: The pilot TNT program yielded 485 HIV tests for 482 individuals through eight generations of recruitment with five (1.0%; 95% CI = 0.4%, 2.3%) new diagnoses. Of these, 246 (51.0%; 95% CI = 46.6%, 55.5%) reported that they had not been tested for HIV within the last 12 months and 383 (79.5%; 95% CI = 75.7%, 82.9%) had not been tested by the existing ED screening program within the last five years. Conclusion: TNT complements population screening by more directly targeting high-risk individuals and by expanding the population receiving testing. Information from existing healthcare services could be used to seed TNT programs, or TNT could be implemented within healthcare settings. Research evaluating multi-component, multi-venue HIV detection is necessary to maximize complementary approaches while minimizing redundancy.