AIDS Research and Therapy最新文献

Background: HTLV-1 is a worldwide distribution retrovirus with 10-20 million infected individuals. ATLL is an Adult T-cell leukaemia lymphoma caused by aggressive T-cell proliferation that is infected by HTLV-1 and is associated with an inferior prognosis. The exact molecular pathogenesis has yet to be fully understood. CREB, a transcription factor, acts as a molecular switch that controls the expression of numerous genes in response to various extracellular signals. Its activation is primarily mediated through phosphorylation by multiple kinases, including MAPKs. MAPKs, a family of serine/threonine kinases, serve as crucial mediators of intracellular signaling cascades.

Method and material: This study investigated, 38 HTLV-I-infected individuals, including 18 HTLV-1 asymptomatic carriers (ACs) and 20 ATLL subjects. mRNA was extracted and converted to cDNA from Peripheral blood mononuclear cells (PBMCs), and then the expression of TAX, HBZ, CREB, and MAPK was analyzed by TaqMan qPCR. The genomic HTLV-1 Proviral loads were examined among the study group.

Results: The data analysis showed a significant difference in the mean of CREB expression amongst study groups (ATLL and carriers, (p = 0.002). There is no statistical difference between the MAPK gene expression (p = 0.35). HBZ, TAX, and HTLV-1 proviral load weree significantly higher in ATLL subjects compared to  ACs  (p = 0.002, 0.000, and 0.000), respectively. Moreover, our results, demonstrated a direct positive correlation among HBZ, CREB, and TAX gene expression in ATLL patients (p = 0.001), whilst between the  ACs, TAX gene expression had a positive significant correlation with HBZ and HTLV-1 proviral load (p = 0.007 and p = 0.004, respectively).

Conclusion: The present study demonstrated that CREB gene expression was higher in the ATLL group than ACs, while there was no difference for MAPK. Therefore, this pathway may not strongly involve in the activation of CREB. The CREB may be a prognostic factor for the development of HTLV-I-associated diseases and can be used as a monitoring marker for the efficiency of the therapeutic regime and prognosis.

Background: Human immunodeficiency virus (HIV) infection is a health problem in Brazil and worldwide. Without treatment, the infection can progress to Acquired Immunodeficiency Syndrome (AIDS), with a high mortality potential. The objective of this study was to analyze the time trend of AIDS mortality in Brazil, macro-regions, federal units and their respective capitals, from 2012 to 2022.

Methods: This is a time-series study of all AIDS deaths in Brazil from 2012 to 2022. The study included the annual number of deaths and the crude and standardized mortality rates. The Joinpoint regression model was used for the time analysis of the standardized rates. Annual percentage change (APC) and average annual percentage change (AAPC) were calculated. A 95% confidence interval (CI) and a 5% significance level were used.

Results: During the period analyzed, 128,678 AIDS deaths were recorded in Brazil, with a crude mortality rate of 6.3/100,000 and a standardized mortality rate of 5.3/100,000. From 2012 to 2020, three regions showed a declining trend in AIDS mortality: Central-West (AAPC - 2.3%; 95%CI -4.3 to -0.21; p = 0.03), Southeast (AAPC - 5.6%; 95%CI -6.8 to -4.0; p < 0.001), and South (AAPC - 4.4%; 95%CI -5.27 to -3.6; p < 0.001). There was also a downward trend in 10 states and 10 capitals. There was an increase in the number of deaths from 2020 onwards in the North, Northeast and Southeast regions compared to 2019.

Conclusion: There was a downward trend in AIDS mortality from 2012 to 2020 and an upward trend from 2020 to 2022. The regional differences observed could reflect the social disparities that exist in Brazil. In addition, the Covid-19 pandemic has had an impact on the process of dealing with HIV in Brazil.

The goal of this study was to describe the cohort of women prescribed PrEP at the Veterans Health Administration. We used a cross-sectional study of electronic health record data. We used descriptive statistics and calculated estimated average percent change by year of prescription. A total of 417 women were prescribed PrEP over the study period. The most substantial change over time in PrEP prescribing occurred among women aged 18-24, in Other race group, and in the Western US. Though PrEP prescribing increased since its approval, more research is needed to identify barriers and expand PrEP access for women Veterans.

Background: Low-level viremia (LLV) (HIV-RNA 51-999 copies/mL) is associated with increased risk of non viral load suppression (HIV-RNA ≥ 1000 copies/mL). We assessed the association between differentiated service delivery model (DSDM) and LLV among people living with HIV (PLHIV) in Rwanda.

Methods: We conducted a retrospective cohort analysis using routinely collected data of adults living with HIV from 28-healthcare facilities in Rwanda before and after the introduction of DSDM. Under DSDM, PLHIV initiated treatment within seven days of HIV diagnosis and medication pick-up up to six months for those with sustained viral load suppression suppression. Proportions of LLV at 6,12 and 18 months were quantified. Multivariable log binomial regression models were used to assess the effect of DSDM on LLV. To handle missing data, multiple imputations was performed.

Results: Of 976 people living with HIV, 645(66.0%) were female and 463(47.4%) initiated treatment during DSDM. The median age was 37 (interquartile range: 32-43) years. LLV was 7.4%, 6.6% and 5.4%, at 6,12 and 18 months, respectively. Compared to those who initiated treatment before DSDM, starting treatment during DSDM increased six-month LLV [adjusted risk ratio (aRR) = 2.8: 95%CI (1.15-6.91)] but not at 12 [aRR = 2.3: 95%CI (0.93-5.75)] and 18 months [aRR = 0.3: 95%CI (0.09-1.20)]. Using imputed datasets, the association between DSDM and LLV persisted.

Conclusions: DSDM was associated with increased risk of LLV at 6-months. possibly due to the minimal amount of time PLHIV had in pondering and accepting the HIV diagnosis. Continued support is needed among people receiving early antiretroviral therapy initiation to prevent development of LLV.

The main objective of the study was to assess the occurrence of non-aids-related comorbidities typical of aging in people living with HIV diagnosis 20 years ago or more and under treatment with antiretroviral drugs for a long time. The associations between the same age group in people living with HIV with reported ART use 20 + years and people living with HIV with reported ART use between two and five years in relation to the risk of comorbidities studied, there was a predominance of metabolic alterations in the 50-60 and 60 + age groups (p < 0.003). The conclusion was that exists a higher risk of comorbidities associated with people living with HIV for more than 20 years, but the length of treatment did not necessarily influence this risk.

Background: Two-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.

Methods: Virologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA^® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.

Results: A total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).

Conclusions: Among virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Aim: This study aimed to assess the impact of Mobile health (M-health) on medication time adherence among people living with HIV/AIDS (PLWHA).

Methods: The study included all PLWHA who were receiving care at the Federal University Teaching Hospital Owerri (FUTH) and Imo State Specialist Hospital (ISSH) Umugumma during the study duration. The test group (FUTH) received a 2-way text message sent three times a week and a once-a-week phone call, while the control group (ISSH) received only the standard care.

Findings: The result shows that the adherence was higher among PLWHA in the test group compared to those in the control group (P = 0.000, χ2 = 168.62, 95% confidence interval (CI): 7.22 to 16.19).

Conclusion: M-health intervention significantly improved the medication time adherence among the participants in the test group compared to those in the control group.

Background: Protease inhibitor (PI)-based Antiretroviral Therapy (ART) regimens are key drugs in HIV management, especially when used as second line drugs. However, some PI-based ART have high adherence demands or tolerable adverse effects which may affect adherence and subsequently viral suppression. We assessed the extent of viral suppression, its determinants, and the experiences of clients on PI-based ART undergoing intensive adherence counselling (IAC) in a public HIV clinic.

Methods: Mixed methods sequential explanatory study involving a quantitative retrospective chart review for clients on PI-based ART who had received IAC from Dec 2016 to May 2023 and qualitative interviews for clients on PI-based ART who had received IAC in the past six months at an urban public HIV clinic in Uganda.

Results: In this study, a total of 189 client charts were included. The median number of IAC sessions received was three (interquartile range, IQR, of 3 to 4) with median time of receiving IAC of three ( IQR, of 2 to 4). One half (51%, 95/186) of the clients had achieved viral suppression and the odds of suppression increased by 30% for every additional month on IAC. Respondents perceived the effectiveness of PI-based ART and IAC in achieving and supporting viral suppression, respectively.

Conclusion: Despite the perceived effectiveness of PI-based ART and IAC, suboptimal levels of viral suppression were observed among clients on PI-based ART who had received IAC. Therefore, it is important to provide IAC for optimal duration as it increases the chances of viral suppression. Further investigation of the barriers of viral suppression for clients on PI-based ART undergoing IAC is needed.

Background: Visceral Leishmaniasis (VL) is the most severe and fatal disease if left untreated. In people living with HIV/AIDS (PLHA), VL is considered an emerging opportunistic infection. The aim of this manuscript was to report a first case in Tunisia of a concomitant presentation of visceral and oral leishmaniasis in a patient LHA. A systematic review of the literature was performed according to PRISMA guidelines, as well.

Case presentation: The patient, a 43-year-old heterosexual man, treated for HIV/AIDS was referred for macrocheilitis of the upper and lower lips. A noticeable nodular and painless swelling extending to the cheeks' mucosa was noted. The patient's poor oral hygiene was evident due to the presence of multiple dental caries. Histological analysis of the biopsied lower lip sample revealed the presence of numerous Leishmania amastigotes. The diagnosis of VL was clinically confirmed by the presence of a mild splenomegaly and pancytopenia and biologically by the identification of the parasite using PCR Lei and the species L. infantum involved using RFLP-PCR and culture. The treatment consisted of an intravenous administration of liposomal Amphotericin B (Ambisome®, 40 mg/kg/weight) for a period of 6 weeks. A favorable outcome was noted after one year with the resolution of clinical symptoms and a negative Leishmania blood PCR test. After 2 years, the patient remained asymptomatic but showed a positive Leishmania blood PCR test. Dolutegravir® was introduced in the patient's ART regimen.

Conclusions: To the best of our knowledge, this is the first case report in Tunisia of atypical VL diagnosed through an uncommon oral location in an HIV/AIDS co-infected patient . Since VL is a severe and potentially fatal disease, it is essential for dentists to perform a thorough clinical examination and adopt a multidisciplinary approach in order to ensure an early diagnosis and an effective treatment outcome.

This study aimed to ascertain how the current two ART regimens used in Ghana affected HIV patients' coagulation profiles. A case-control study was conducted on 102 HIV positive patients at the Mampong Municipal Hospital. Coagulation parameters measured showed APTT was normal in majority of ART-experienced participants but prolonged in majority of ART-naïve participants. The mean platelet count was significantly higher in ART-experienced participants. No significant differences were found between the coagulation profiles of ART-experienced patients on two different drug regimens. In conclusion, current ART can enhance the coagulation profiles in HIV-infected patients, by improving platelet count and APTT.