Current HIV Research - Volume 17, Issue 4, 2019

AIDS is a globalized infectious disease. In 2014, UNAIDS launched a global project of “90-90-90” to end the HIV epidemic by 2030. The second and third 90 require 90% of HIV-1 infected individuals receiving antiretroviral therapy (ART) and durable virological suppression. However, wide use of ART will greatly increase the emergence and spreading of HIV drug resistance and current HIV drug resistance test (DRT) assays in China are seriously lagging behind, hindering to achieve virological suppression. Therefore, recommending an appropriate HIV DRT method is critical for HIV routine surveillance and prevention in China. In this review, we summarized the current existing HIV drug resistance genotypic testing methods around the world and discussed the advantages and disadvantages of these methods.

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.

Background: Patient registries represent a long-term data collection system that is a platform for performing multiple research studies to generate real-world evidence. Many of these registries use common data elements (CDEs) and link data from Electronic Health Records. Objective: This study evaluated HIV registry features that contribute to the registry’s usability for retrospective analysis of existing registry data or new prospective interventional studies. Methods: We searched PubMed and ClinicalTrials.gov (CTG) to generate a list of HIV registries. We used the framework developed by the European Medical Agency (EMA) to evaluate the registries by determining the presence of key research features. These features included information about the registry, request and collaboration processes, and available data. We acquired data dictionaries and identified CDEs. Results: We found 13 HIV registries that met our criteria, 11 through PubMed and 2 through CTG. The prevalence of the evaluated features ranged from all 13 (100%) having published key registry information to 0 having a research contract template. We analyzed 6 data dictionaries and identified 14 CDEs that were present in at least 4 of 6 (66.7%) registry data dictionaries. Conclusion: The importance of registries as platforms for research data is growing and the presence of certain features, including data dictionaries, contributes to the reuse and secondary research capabilities of a registry. We found some features such as collaboration policies were in the majority of registries while others such as, ethical support, were in a few and are more for future development.

Background: Women face unique complexities in HIV treatment yet are underrepresented in antiretroviral therapy (ART) studies. Objective: This analysis assessed the one-year durability of the first integrase strand transfer inhibitor (INSTI)-based regimens prescribed to women in a large cohort of patients living with HIV in care. Methods: Women with HIV who initiated their first INSTI-containing regimen between 08/12/2013 and 11/30/2015 were identified in the OPERA cohort, a collaboration of 79 US outpatient clinics. Discontinuation within the first year of treatment with an INSTI was compared between dolutegravir (DTG), raltegravir (RAL) and elvitegravir (EVG), using multivariable Cox regression and Kaplan- Meier estimates. Virologic response and regimen modifications were described and compared across INSTIs. Results: A total of 537 treatment-naïve (DTG: 39%, EVG: 48%, RAL: 13%) and 878 treatmentexperienced (DTG: 57%, EVG: 29%, RAL: 13%) women were analyzed. In the first twelve months after initiation, women taking EVG or RAL were more likely to discontinue their initial INSTI than those taking DTG among both treatment-naïve (adjusted hazard ratio EVG vs. DTG: 1.59 (95% CI: 1.09, 2.39); RAL vs. DTG: 2.46 (1.49, 4.05)) and treatment-experienced women (EVG vs. DTG: 1.39 (1.02, 1.88); RAL vs. DTG: 2.17 (1.51, 3.12)). Following discontinuation of the initial INSTI, women commonly switched to a regimen containing a different drug from the INSTI class (treatment-naïve DTG: 34%, RAL: 33% EVG: 41%; treatment-experienced DTG: 23%, RAL: 19% EVG: 41%). Conclusion: In treatment-naïve and treatment-experienced women living with HIV, women taking DTG had the lowest risk for early (≤1 year) discontinuation.

Objective: To estimate the number of 15-79-year-old individuals infected with HIV in the Santa Catarina state, Brazil, during the period 2008-2017. Methods: Three official registers of the HIV-infected individuals were compiled: SINAN for the HIV/AIDS epidemiological surveillance, SIM for mortality and SISCEL for the HIV viral load and CD4/CD8 cell count. Their records were linked by a unique personal identifier. Capture-recapture estimates were obtained by log-linear modelling with both the main effects and interaction between the registers, adjusted for age, sex and period. An adjustment for underreporting of AIDS-related deaths used published data on ill-defined causes of death and AIDS mortality. Results: After data sorting, 67340 HIV/AIDS records were identified: 29734 (44.2%) by SINAN, 5540 (8.2%) by SIM and 32066 (47.6%) by SISCEL. After record linkage, the HIV population size was estimated at 45707, whereas the capture-recapture method added 44 individuals. The number of new HIV/AIDS notifications per year increased significantly in 2014-2017 compared to the period 2011-2013 among 15-34-year-old men and less so for older men and women. Including 1512 unreported AIDS-related deaths gave an estimated 47263 HIV-infected individuals with 95% confidence interval (CI) of 47245-47282 and corresponding incidence of 93 (95% CI 91-96) p/100000. Case ascertainment of 62.9%, 78.5% and 67.8% was estimated for SINAN, SIM and SISCEL, respectively. Conclusion: Three major HIV/AIDS registers in Brazil showed significant under-notification of the HIV/AIDS epidemiological surveillance amenable to significant improvement by routine record linkage.

Background: The abuse of psychostimulants such as methamphetamine (METH) is common in human immunodeficiency virus (HIV)-infected individuals. Acquired immunodeficiency syndrome (AIDS) patients taking METH and antiretroviral drugs could suffer severe neurologic damage and cognitive impairment. Objective: To reveal the underlying neuropathologic mechanisms of an HIV protease inhibitor (PI) combined with METH, growth-inhibition tests of dopaminergic cells and RNA sequencing were performed. Methods: A combination of METH and PI caused more growth inhibition of dopaminergic cells than METH alone or a PI alone. Furthermore, we identified differentially expressed gene (DEG) patterns in the METH vs. untreated cells (1161 genes), PI vs. untreated cells (16 genes), METH-PI vs. PI (3959 genes), and METH-PI vs. METH groups (14 genes). Results: The DEGs in the METH-PI co-treatment group were verified in the brains of a mouse model using quantitative polymerase chain reaction and were involved mostly in the regulatory functions of cell proliferation and inflammation. Conclusion: Such identification of key regulatory genes could facilitate the study of their neuroprotective potential in the users of METH and PIs.