Aids Research and Human Retroviruses

Journal Information
ISSN / EISSN: 08892229 / 19318405
Total articles ≅ 7,547

Latest articles in this journal

Rosario Quiroga Ferrufino, Ana Luiza Bierrenbach, Camila Rodrigues, Gerusa Maria Figueiredo, Daniel Gleison, Silvia Yapura, Maria Laura Mariano de Matos, Ricardo Vasconcelos, Steven Sol Witkin,
Published: 29 November 2022
Aids Research and Human Retroviruses; https://doi.org/10.1089/aid.2021.0197

Abstract:
Introduction : Identification of mechanisms of hepatitis C virus (HCV) acquisition among HIV-infected people is critical for prevention guidance. The aim of this study was to investigate risk factors for HCV infection and variations in HCV genotype distribution in a cohort of HIV-HCV co-infected patients in Brazil. Methods : This was a cross-sectional, observational epidemiological study of a cohort of HIV-HCV co-infected individuals seen at a referral center for HIV-infected patients in the city of São Paulo between January and December 2017. The time of HCV acquisition, as determined by chart review, was categorized as before 2000, between 2000 and 2009, and from 2010 onwards. HCV genotypes were determined by gene amplification and analysis. Results and discussion : Among 3143 HIV-infected individuals analyzed, 362 (11.5%) were HCV-HIV co-infected. Overall, the reported modes of HCV acquisition were: sexual exposure in 172 (47.5%), injection drug use (IDU) in 86 (23.8%), use of inhaled drugs in 67 (18.5%) and blood transfusion in 10 (2.8%) individuals. All individuals who acquired HCV following IDU became infected prior to 2010. HCV acquisition by sexual contact was reported by 26.4%, 65.9% and 63.8% of patients before 2000, between 2000 and 2009, and from 2010, respectively. There was an increase (p<0.001) in the proportion of cases due to sexual transmission from the period before 2000 (26.4%) to between 2000 and 2009 (65.9%). There was no corresponding increase from 2000 and 2009 to after 2010 (p=0.751). HCV genotype 1 was most prevalent at all time periods. The genotype 3 frequency decreased over time (test for trend p<0.001), while genotype 4, extremely uncommon before 2010 became the second most prevalent genotype from 2010 onwards. Conclusions : In HIV infected individuals in Sao Paulo, Brazil, sexual transmission has replaced IDU as the most frequent mode of HCV acquisition.
Inderpal Singh, Saul Tzipori
Published: 24 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0091

Abstract:
Microsporidiosis caused by E. bieneusi is a common opportunistic infection in patients with HIV/AIDS and those on immunosuppressive therapy. A significant loss of mucosal or peripheral CD4+ T cells and subsequent dysfunction of the intestinal immune system may be responsible for the development of chronic microsporidiosis in these patients. We have used the SIV-infected macaque model to investigate this relationship. To establish the course of E. bieneusi infection in SIV-infected animals, four SIV-infected animals were experimentally challenged with E. bieneusi when their CD4+ counts dropped to less than 300 cells/μl of blood. Analysis of fecal samples by nested PCR revealed that 3 out of 4 E. bieneusi-infected macaques continued to shed spores for 7-24 months after infection, an indication of chronic microsporidiosis. Four other SIV-infected macaques, after having an initial negative phase, spontaneously acquired E. bieneusi infection when their CD4+ counts dropped to less than 600 cells/μl of blood and shed spores for 8-19 months. The shedding of E. bieneusi spores in the feces increased relative to decrease in peripheral blood CD4+ T cell numbers. Gut biopsies were obtained before and after challenge to phenotype the mucosal lymphocyte subsets using flow cytometry. The immunophenotypic analysis showed no restoration of CD4+ T cells after E. bieneusi infection in the intestinal cells. A slight increase in the percentage population of CD4+ T cells in peripheral blood did not have any effect on the control of E. bieneusi infection in the SIV-infected macaques. These preliminary studies demonstrate that SIV-infected macaques develop chronic E. bieneusi infections as their CD4+ counts dropped to below 300 cells/μl of blood.
Lorna Leal, Alberto C Guardo, Luis Miguel Bedoya, Ms. Cristina Rodríguez de Miguel, Nuria Climent, Ms. Cristina Rovira, Ms. Manuela Beltrán, Josep Llach, Jose Alcami, Angela Kashuba, et al.
Published: 23 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2021.0232

Abstract:
Most of the studies using the colorectal tissue explants challenge model have been conducted after one single-dose and before reaching a steady-state. We consider that longer exposure as in 28-day post-exposure prophylaxis (PEP) course and in an at-risk setting, such as after a sexual risk exposure to HIV could give us valuable information about these drugs. In a substudy we assessed pharmacokinetics, changes on immune system and ex-vivo rectal mucosal susceptibility to HIV-1 infection after taking maraviroc (MVC), raltegravir (RAL) and ritonavir-boosted lopinavir (LPV/r) PEP-based regimens in 30 men who have sex with men. Participants received 28 days of twice-daily MVC (n=11), RAL (n=10) or LPV/r (n=9) all with tenofovir/emtricitabine backbone. Blood, rectal fluid (RF) and rectal tissue (RT) samples were collected at day 7, 28 and 90 after starting PEP. The samples obtained at day 90 were considered baseline. All studied antiretrovirals were quantifiable at 7 and 28 days in all tissues. Activation markers were increased in CD4 mucosal mononuclear cells (MMC) after 28 days of MVC: CD38+ 68.5 vs 85.1, p=0.008 and CD38+DR+ 16.1 vs 26.7, p=0.008. Exposure to MVC at both end-points (7 and 28 days) was associated with significant suppression of HIV-1BAL (p=0.005 and p=0.028) but we did not observe this effect with RAL or LPV/r. Merging together changes in MMC in all arms, we found a positive correlation in the CD8 T-cell lineage between the infectivity at day 7 and activation (CD38+ r=0.43, p=0.025, DR+ r=0.547, p=0.003 and 38+DR+ r=0.526, p=0.05), senescence (CD57+CD28- r=0.479, p=0.012), naïve cells (RA+CCR7+ r=0.484, p=0.01) and CCR5 expression (r=0.593, p=0.001). We conclude that maraviroc in combination with tenofovir/emtricitabine was associated with viral suppression in rectal explants and that overall ex-vivo HIV infectivity correlated with activation and senescence in CD8 mucosal mononuclear cells.
Charalampos Moschopoulos, Konstantinos Protopapas, Konstantinos Thomas, Dimitra Kavatha, Antonios Papadopoulos, Anastasia Antoniadou
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0086

Abstract:
In the era of combination antiretroviral therapy (ART), people living with HIV (PLHIV) still face an increased risk of cardiovascular disease (CVD). Tenofovir alafenamide fumarate (TAF) is superior to its precursor tenofovir disoproxil fumarate (TDF) regarding bone and renal toxicity, but there are concerns about a negative effect on lipid profile. This observational, single-center study investigates the effects on lipid profile and cardiovascular (CVD) risk of the switch from TDF to TAF, in combination with FTC/EVG/c, in patients with no exposure to other antiretrovirals. Routine laboratory measurements, somatometric characteristics and smoking status were analyzed for the assessment of CVD risk changes, using D:A:D and ATP III scores pre- and post-switch. A total of 62 patients with a mean age of 32.9 years were included in this study. 61 (98.4%) were males, 38 (61.3%) late presenters and 39 (62.9%) active smokers. A year after the switch, there was a significant increase in total cholesterol (178±38 to 194±40 mg/dL, p<0.001), HDL (45±12 to 48±13 mg/dL, p=0.001), LDL (117±32 to 137±36 mg/dL, p<0.001). Mean increase of the 10-year D:A:D score was 1.13% (95% CI 1.05-1.22, p=0,002). Changes were more prominent in non-smokers. Body mass index and average weight showed an upward trend. Switching from TDF to TAF caused significant changes in lipid profile at 14 months of follow-up, in young, otherwise healthy PLHIV. CVD risk, as measured by D:A:D, showed a statistically significant increase, but more data are needed to determine clinical significance. These results point towards a patient-centered approach when selecting an ART regimen.
Peter Wesley Young, Paul Musingila, Leonard Kingwara, Drew Voetsch, Emily Zielinski-Gutierrez, Marc Bulterys, Andrea A Kim, Ms. Megan A. Bronson, Bharat Parekh, Ms. Trudy Dobbs, et al.
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0054

Abstract:
Background: Nationally-representative surveys provide an opportunity to assess trends in recent HIV infection based on assays for recent HIV infection. Methods: We assessed HIV incidence in Kenya in 2018 and trends in recent HIV infection among adolescents and adults in Kenya using nationally representative household surveys conducted in 2007, 2012 and 2018. To assess trends, we defined a recent HIV infection testing algorithm (RITA) that classified as recently infected (<12 months) those HIV-positive participants that were recent on the HIV-1 limiting antigen (LAg)-avidity assay without evidence of antiretroviral use. We assessed factors associated with recent and long-term (≥12 months) HIV infection versus no infection using a multinomial logit model while accounting for complex survey design. Findings: Of 1,523 HIV-positive participants in 2018, 11 were classified as recent. Annual HIV incidence was 0.14% in 2018 (95% confidence interval [CI] 0.057–0.23), representing 35,900 (95% CI 16,300–55,600) new infections per year in Kenya among persons aged 15–64 years. The percentage of HIV infections that were determined to be recent was similar in 2007 and 2012 but fell significantly from 2012 to 2018 (adjusted odds ratio [aOR]=0.31, p<0.001). Compared to no HIV infection, being aged 25–34 versus 35–64 years (aOR=4.2, 95% CI 1.4–13), having more lifetime sex partners (aOR=5.2, 95% CI 1.6–17 for 2–3 partners and aOR=8.6, 95% CI 2.8–26 for ≥4 partners versus 0–1 partners), and never having tested for HIV (aOR=4.1, 95% CI 1.5–11) were independently associated with recent HIV infection. Interpretation: Though HIV remains a public health priority in Kenya, HIV incidence estimates and trends in recent HIV infection support a significant decrease in new HIV infections from 2012 to 2018, a period of rapid expansion in HIV diagnosis, prevention, and treatment.
Ms. Xiangyun Tang, Meng Liu, Ning An, Ms. Xinyu Zhang, Yingying Wang, Yan Li, Qi Li, Xinli Lu
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0124

Abstract:
Two near full-length genome (NFLG) sequences of HIV-1 with undefined subtypes were analyzed to confirm the recombinant characteristics. In order to analyze the gene recombination patterns and breakpoints of these two NFLGs, the phylogenetic trees based on the NFLG sequences and their subregions were constructed, respectively. Sequences 233 and 953 are novel second-generation recombinant forms of HIV-1 CRF01_AE and subtype B. The NFLG phylogenetic tree analysis showed that these two NFLG sequences formed a unique monophyletic branch, respectively. The recombination breakpoints analysis showed that the recombination pattern of both sequences was that a subtype B fragment was inserted into a CRF01_AE backbone. Subregions I, II and III were from CRF01_AE, subtype B and CRF01_AE, respectively. The recombination breakpoints relative to HXB2 of sequences 233 and 953 were 2400 and 4870, and 3363 and 4828, respectively. The emergence of novel recombinant forms of CRF01_AE/B demonstrates that we should carry out the ongoing surveillance of HIV-1 recombinant forms in sexually transmitted population.
Daniel John, Peng Wang, Yaya Togo, Mark McGovern
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0068

Abstract:
Introduction: Improving access to grant funding is a critical aspect of strengthening research capacity outside of higher-income settings, particularly in HIV/AIDS where randomized control trials that require substantial resources are common. In this paper, we assessed recent RCTs to examine variation in how studies were funded, depending on study location and countries where publication authors were based. Methods: We conducted a Pubmed literature review to identify RCTs with HIV status or viral load endpoints published in 2019 and 2020, then analysed cross-tabulations of funding sources by study characteristics. Results: 116 publications met the inclusion criteria. Research in higher income countries was most likely to be funded by biotech/pharmaceutical companies, while research in lower- and middle-income countries was most likely to be funded by US government sources. Overall, we found the distribution of funding sources differed significantly by study and author location (χ^2=23, P < 0.001). Conclusions: Published RCTs with HIV status or viral load endpoints are financed differently based on where studies take place and where the authors are based. As part of future research, understanding why this variation exists is critical for assessing how funding contributes to global imbalances in scientific resources.
Vurayai Ruhanya, Graeme Brendon Jacobs, Robert H. Paul, John Joska, Soraya Seedat, George Nyandoro, Richard Glashoff, Susan Engelbrecht
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0022

Abstract:
There is increasing evidence that HIV-1 viral protein R (Vpr) plays an important role in the pathogenesis of cognitive impairment. We investigated the relationship between HIV-1 sub-type C Vpr sequence variation and HIV-associated neurocognitive impairment as measured by global deficit score (GDS) in treatment naive individuals. We used different bioinformatic tools and statistical models to correlate vpr variation and cognitive function. We identified a Tyrosine at position 45 (45Y) as signature for neurocognitive impairment and Histidine (45H) as a signature in the non-impaired indviduals. The presence of signature 45Y was associated by 3.66 times higher GDS, 525 times higher plasma viral load, 15.84 times higher proviral load and 60% lower absolute CD4-T cell count compared those without the signature. Additionally, we identified 4 conserved Vpr fragment sequences, PEDQGPQREPYNEWTLE (5 to 21), LGQYIY(42 to 47), TYGDTW (49 to 54), PEDQGPQREPYNEW (5 to 18) that were associated with higher plasma viral load and proviral load. The implication of these findings is that variation of Vpr leads to neurocognitve impairment in HIV infection and worsens the progression of disease in general by promoting the production of provirus, promoting HIV replication and depletion of CD4+ T cells in the periphery. Key words: HAND, Vpr, entropy, signature amino acid residue, Tyrosine, Histidine,
Eitan Grinsteiner, Mary Morrow, Ms. Samantha MaWhinney, Ryan P. Coyle, Ms. Stacey Coleman, Jia-Hua Zheng, Lucas Ellison, Lane R. Bushman, Jennifer J. Kiser, Peter L. Anderson, et al.
Published: 18 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2021.0218

Abstract:
The potency of modern antiretroviral therapy (ART) allows for greater forgiveness to missed doses while still achieving, and maintaining, viral suppression. However, imperfect ART adherence, even if sufficient to maintain viral suppression, has been associated with adverse clinical outcomes. ART adherence can be objectively quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a biomarker of cumulative adherence that is predictive of future viremia- even among persons with HIV (PWH) with an undetectable HIV viral load (HIV VL). Within a prospective cohort of PWH on tenofovir disoproxil fumarate (TDF)-including ART, mismatch between drug concentration and HIV VL (i.e., low concentrations of TFV-DP in DBS in the setting of viral suppression with subsequent viremia at the following visit) was observed more frequently in PWH who were Black (36% vs. 15%; p=0.04), had BMI >30 kg/m2 (40% vs. 13%; p=0.01), and reported <100% 3mo (68% vs. 50%; p=0.005) and 30d (56% vs. 31%; p=0.001) adherence, compared to PWH without mismatch. Identifying PWH at risk for future viremia could help clinicians implement targeted, timely interventions prior to episodes of breakthrough viremia.
, Kazuhiko Ikeuchi, Michiko Koga, Hiroshi Yotsuyanagi
Published: 17 November 2022
AIDS Research and Human Retroviruses; https://doi.org/10.1089/aid.2022.0115

Abstract:
It is not clear if there is a difference between 3-drug regimens (3DR) and 2-drug regimens (2DR) in terms of suppression of chronic inflammation. We compared CRP, CD4+/CD8+ ratio, lipid proliges measured in daily clinical practice before and after the switch to dolutegravir plus lamivudine (DTG/3TC) to examine the difference in the anti-inflammatory effect of 3DR and 2DR. In this single-center, retrospective, observational study, individuals who were on abacavir/lamivudine/dolutegravir (ABC/3TC/DTG), Tenofovir alafenamide/emtricitabine (TAF/FTC) plus DTG, or bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) prior to switching to DTG/3TC, were eligible. A total of 119 individuals were enrolled in the study. The median (IQR) time since diagnosis of HIV infection was 12 (7-16) years. Overall, inflammation markers such as CD4+/CD8+ ratio, CD4+, CRP and lipid profiles did not change. Analysis of only individuals who switched from ABC/3TC/DTG, TAF-based regimens also showed no significant changes in inflammatory markers. Since viremia raises inflammatory markers, differences in antiviral efficacy may make a difference in the suppression of chronic inflammation but in conclusion, we did not find any change in inflammatory markers by changing from 3DR to 2DR in daily clinical practice.
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