AIDS Research and Therapy最新文献

Background: Hepatitis C virus (HCV) coinfection may further compromise immunological and cognitive function in people with HIV (PWH). This study compared laboratory and neuropsychiatric measures across the periods of HCV seroconversion and direct-acting antiviral (DAA) therapy with sustained virologic response (SVR) among PWH who initiated antiretroviral therapy (ART) during acute HIV infection (AHI) and acquired HCV after 24 weeks of ART.

Methods: Participants from the RV254 AHI cohort underwent paired laboratory and neuropsychiatric assessments during follow-up visits. The former included measurements of CD4 + and CD8 + T-cell counts, HIV RNA, liver enzymes, and lipid profiles. The latter included the Patient Health Questionnaire-9 (PHQ-9), Distress Thermometer (DT), and a 4-test cognitive battery that evaluated psychomotor speed, executive function, fine motor speed, and dexterity. The raw scores in the battery were standardized and averaged to create an aggregate performance (NPZ-4) score. Parameters of HCV-coinfected participants were compared across the periods of HCV seroconversion and DAA treatment.

Results: Between 2009 and 2022, 79 of 703 RV254 participants acquired HCV after ≥ 24 weeks of ART; 53 received DAA, and 50 (94%) achieved SVR. All participants were Thai males (median age: 30 years); 34 (68%) denied past intravenous drug use, and 41 (82%) had a history of other sexually transmitted infections during follow-up. Following SVR, aspartate transferase (AST) and alanine transaminase (ALT) decreased (p < 0.001), while total cholesterol, low-density lipoprotein, and triglycerides increased (p < 0.01). The median CD4 + /CD8 + ratio increased from 0.91 to 0.97 (p = 0.012). NPZ-4 improved from 0.75 to 0.91 (p = 0.004). The median DT score increased from 1.7 to 2.7 (p = 0.045), but the PHQ-9 score remained unchanged.

Conclusion: HCV coinfection is common in this group of high-risk PWH, highlighting the need for regular screening, early diagnosis, and treatment. The study participants exhibited a modest improvement in the CD4 + /CD8 + T-cell ratio and cognitive performance following DAA therapy and SVR. Future studies should examine potential neuropsychiatric impacts during early HCV infection as well as the longer-term neuropsychiatric outcomes after DAA treatment with SVR.

Background: Advanced HIV disease (AHD) is still a significant problem in Uganda despite the test-and-treat strategy and the increased access to antiretroviral therapy (ART). Meningitis remains a major cause of morbidity and mortality in people with AHD. HIV counselling is essential and plays an important role in managing persons with AHD-related meningitis. We sought to describe the experiences and challenges we faced during counselling of these individuals, highlighting the strategies, gaps and how we can fill them.

Methods: First, we describe our experience and major challenges in counselling people with AHD-related meningitis. Second, we describe the strategies we used to overcome each of these challenges. Third, we highlight the health system gaps and recommend solutions.

Results: Major challenges include the presence of altered mental status, unknown HIV status at admission, non-disclosure of HIV status to family, insufficient ART history, caretakers-related challenges, pill burden, multiple drug side effects, invasive clinical procedures, myths about medical procedures, poverty, lack of privacy during counselling in the wards, patients/caretakers seeking alternative non-medical interventions including religious, traditional, and herbal therapies before and after initiating meningitis treatment.

Conclusions: Persons with AHD-related meningitis need daily and special consideration during counselling as part of the package of care to improve treatment outcomes.

Trial registrations: NCT01075152 (23 Feb 2010), NCT01802385 (28 Feb 2013), ISRCTN42218549 (24 April 2018), ISRCTN72509687 (13 July 2017), NCT04031833 (01 January 2019), ISRCTN15668391 (23 May 2019), ISRCTN18437550 (05/11/2021).

Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven lymphoproliferative disease that usually arises in the context of reduced immunological surveillance. Based on histology, two forms of the disease are recognized, namely low-grade and high-grade LYG. Clinically, LYG universally involves the lungs and, frequently, also the skin, central nervous system, liver, and kidneys. Here, we present the case of a 55-year-old woman with a difficult-to-diagnose low-grade LYG with symptomatic lung involvement, who concomitantly was newly diagnosed with human immunodeficiency virus (HIV) infection. Rapid immune recovery achieved through antiretroviral therapy led to a complete and sustained clinical and radiological remission of LYG.

Globally HIV remains a major public health problem. In sub-Saharan Africa most new HIV infections occur in adolescent girls and young women. Previously tested antiretroviral drugs as different pre-exposure prophylaxis (PrEP) formulations have shown inconsistent levels of protection against HIV in African women. Besides adherence, biological factors such as drug transporter proteins are increasingly recognized as key modulators of PrEP levels. Drug transporter mRNA expression levels has been significantly correlated to altered PrEP levels in-vitro in different tissues, with inflammation identified as a further modifier of drug transporters mRNA expression and thus PrEP levels. We therefore, aimed to determine possible concordance between drug transporter mRNA expression in the female genital tract (FGT) and blood of N = 45 South African women taking oral PrEP-Truvada® [TDF/FTC)] over 6 months for HIV prevention. Additionally, we determined associations between drug transporter mRNA expression, genital inflammation, and blood-tenofovir diphosphate (TFV-DP). mRNA-expression of four efflux P-gp; MATE-1; MRP-2; MRP-4 and two influx OAT-1 and OAT-3 drug transporters were determined by qRT-PCR. Multiplexed technology was used to measure 27 cytokines to define genital inflammation. Significant positive correlations of mRNA expression for P-gp, MATE-1, MRP-2, and MRP-4 were observed between the FGT and blood at 3- and 6-months post-PrEP initiation (p < 0.05). For OAT-1 however, significant positive correlations were observed pre- and post-PrEP exposure (p < 0.05). Linear-mixed models showed moderate associations between FGT cytokines and drug transporter mRNA expression, with a  direct relationship observed between MIP-1β concentration and MATE-1 mRNA expression. Similarly, PLS-DA showed that in women with genital inflammation, consistently higher mRNA expression of MATE-1 was observed compared to women without genital inflammation. No significant associations were observed between drug transporter mRNA expression and blood TFV-DP. Our results suggest that drug transporters may be similarly expressed in the FGT and blood. Furthermore, genital inflammation may modify PrEP levels by altering drug transporter mRNA expression. Collectively, our data may be used to better understand biological factors that may affect PrEP efficacy in African women who remain vulnerable to HIV.

Background: Anal cancer incidence is increased in people with HIV (PWH), up to 60 times higher in men who have sex with men, and almost 15 times higher among women with HIV. Screening and treating high-grade lesions (HSIL) have proven to reduce the incidence of invasive anal cancer. In 2020, we started implementing a high-resolution anoscopy (HRA) clinic at INCan, a tertiary care oncologic center, as part of a screening program for PWH from the HIV clinic.

Objectives: We describe the barriers and difficulties in implementing an HRA Clinic from January 2020 to April 2021, including physician training, the certification process, discrepancies between cytology and histopathologist results, and the lack of experience of gastrointestinal pathologists in HPV-related lesions.

Results: During the first 18 months of the HRA clinic implementation, 124 studies were performed, and 85 biopsies were done. The prevalence of HSIL was 22%. Initially, when a gastrointestinal pathologist reviewed anal canal biopsies, a second opinion was requested from a genitourinary pathologist who examined 72 of the biopsies; there were discrepancies in the diagnosis in 61% of the cases, with more advanced intraepithelial lesions in 43% of cases. Specifically, gastrointestinal pathologists missed 68% of HSILs. The difficulties we faced were not having access to adequate anoscopes. Training and certification are a long way to go. Also, women's reachability was low.

Conclusions: Diagnosis and management of anal HSIL have become a standard of care in the prevention of Anal Carcinoma in PWIH, the population with the highest incidence of this neoplasia. Implementing HRA programs requires correct supplies and equipment, which are not always locally available; investing in physicians' training and an experienced pathologist in HPV-associated lesions interpretation is also imperative. More advocacy is needed for HIV programs to incorporate and invest in anal cancer screening.

Background: Few reports have focused on renal cell carcinoma (RCC) in the people with HIV(PWH).

Methods: We analyzed patients diagnosed with RCC at our center between January 2011 and June 2024, divided into groups based on their HIV status. Categorical variables were compared using the chi-square test, and continuous variables were analyzed with the t-test. We estimated median and 1-, 3-, and 5-year cancer-specific survival (CSS) using Kaplan-Meier curves and conducted univariate and multivariate Cox analyses to evaluate variables associated with CSS.

Results: In total, 144 RCC patients were assigned to either PWH group (n = 48) or PWoH (people without HIV) group (n = 96). Patients in the PWH group were significantly more likely to be male (91.7% vs. 71.8%, p = 0.014), and their median age was 7 years younger than that in the PWoH group (51 vs. 58 years, p < 0.01). Both groups had small-diameter, early-stage, low-grade tumors, with no significant differences in short-term outcomes. Higher tumor stage (> T1 vs. T1: hazard ratio = 8.621, 95% confidence interval = 3.76-20, p < 0.01) and larger tumor diameter (≥ 7 vs. <7 cm: hazard ratio = 3.525, 95% confidence interval = 1.697-7.321, p < 0.01) were significantly associated with CSS, whereas the HIV status did not significantly affect long-term survival.

Conclusions: RCC tends to be diagnosed at a younger age in PWH, highlighting the need for earlier RCC screening in this population. The HIV status does not affect postoperative recovery, short-term outcomes, or long-term survival in patients with RCC.

Introduction: Data about impact of switch to dolutegravir (DTG)-based antiretroviral therapy (ART) on estimated glomerular filtration rate (eGFR) in Asians are scarce. RV254/SEARCH010 is a prospective observational cohort in Bangkok, Thailand with ART initiation during acute HIV infection (AHI) where participants switched to DTG-based ART.

Methods: Participants started Efavirenz (EFV)-based ART during AHI (n = 214) and switched to DTG-based ART after a median of 97 weeks (IQR 61-145). GFR was estimated by serum creatinine (eGFR_cre) every 24 weeks before and after switch. Estimated GFR by cystatin C (eGFR_cystC) was ordered at clinician's discretion for decreased eGFR_cre after switch. Random-effect linear regression model was used to assess changes in eGFR_cre over 96 weeks from starting ART, and from switching to DTG.

Results: At study entry, 20 participants (9.3%) had eGFR_cre < 90 ml/min/1.73 m². During EFV-based ART, an additional 17 (8%) developed eGFR_cre < 90 ml/min/1.73 m², nearly all transient, while mean eGFR_cre remained stable and within normal range. At switch to DTG, 21 (9.8%) had eGFR_cre < 90 ml/min/1.73 m² but an additional 116 (54%) developed eGFR_cre < 90 ml/min/1.73 m² during follow-up with eGFR_cre decrease being mostly persistent. Mean eGFR_cre decreased 20.8% from 117.0 to 92.4 ml/min/1.73 m² (p < 0.001). Among 20 post-switch participants with eGFR_cystC measured within 4 weeks of eGFR_cre < 90 mL/min/1.73 m², 13 (65%) had normal kidney function by eGFR_cystC.

Conclusions: Persistent eGFR_cre decrease to < 90 ml/min/1.73 m² after switch to DTG was common in this Thai population. eGFR_cystC was helpful to identify individuals with clinically significant decrease in kidney function and obviate unnecessary ART modifications. Trial registration Clinical Trials Registry Number: ClininicalTrials.gov NCT00796146.

Aim: HIV remains one of the major epidemics and public health concerns within low and middle-income countries such as Tanzania. This study aimed to assess the prevalence and the factors associated with HIV testing-seeking behaviors among women of childbearing age in Tanzania.

Methods: This study used the 2022 Tanzania Demographic and Health Survey dataset. The study utilized individual recodes (IR) files where data was collected using the Women's Questionnaire to analyze factors influencing HIV testing behavior among women, Descriptive analysis, and bivariate and multivariate logistic regressions were performed and all the data were processed and analyzed using STATA version 17 at 95% CI and significance level P < 0.05.

Results: This study included 2531 women with 90.0% having ever tested for HIV while 7.0% had never tested for HIV. Not employed [AOR:0.35, CI (0.20-0.61)] has lower odds of HIV testing than All-year employed status. Rural residents have reduced odds of HIV testing [AOR:0.43, CI (0.21-0.88)] compared to women living in urban areas. Those able to ask their partner to use a condom are more likely to have been tested with increased odds [AOR: 3.52, CI (2.31-5.37)]. Participants with a history of genital discharge [AOR:4.30, CI (1.28-14.46)] and those who don't know their genital discharge history have [AOR: 0.20, CI (0.07-0.55)] are significant for HIV testing. Women who have heard about PrEP but are not uncertain about its approval [AOR: 36.07, CI (3.33-390.25)], respondents who have tested before with HIV testing kits [AOR:35.99, CI (4.00-324.13)] and women who are aware of HIV testing kids but never tested with them before [AOR: 2.80, CI (1.19-6.58)] are predictors of HIV testing seeking behaviors.

Conclusion: The government and other concerned agencies should introduce mobile or community-based testing units and subsidize testing costs to reach economically disadvantaged or rural populations. Promote Open Communication on Sexual Health: Public health campaigns should encourage open discussions about sexual health within relationships, emphasizing condom negotiation and mutual health checks as preventive measures. Raise Awareness and Accessibility of HIV Prevention Tools: Expand education on PrEP and HIV self-test kits to improve familiarity and acceptance, which may empower individuals to proactively seek testing. Integrate Sexual Health Screening into Routine Healthcare: Health facilities should incorporate HIV testing when individuals present with symptoms like genital discharge to improve early detection and intervention.

Background: Health literacy (HL)has been identified as one of the important determinants of healthy behaviors and the health of individuals and communities. The global attempts to control the HIV disease were emphasized, in the midst the new coronavirus disease (COVID-19) emerged as a pandemic. This study aimed to determine HL level and its relationship with COVID-19-prevention behaviors among people living with HIV(PLWH).

Methods: This cross-sectional study was conducted on 112 PLWH referred to behavioral disorders consulting center in Arak, Iran from May to December 2022. The data collection tool was a questionnaire including COVID-19 prevention behaviors (5 items) and a health literacy instrument (14 items). The data were analyzed using SPSS software version 18 and for all tests, the significance level of α was considered as 0.05.

Results: The average (SD)age of the participants was 42.9 (10.6) and the education level of 11.6% of the participants were university. The mean score of HL was 3.5 (0.73) out of 5 and 36.6% of them had higher HL. The mean of behaviors was 17.2 (3.4) out of 25 and 53.6 had higher behaviors. The HL had a significant relationship with behaviors (r = 0.48; p < 0.001). Multiple linear regression indicated that HL had a significant association with age (P = 0.002), education (P = 0.046), and economic status (p < 0.001) and explained 32% of the variance of HL.

Conclusion: According to the findings, HL affected COVID-19-prevention behaviors. Effective educational interventions intended for PLWH based on health literacy can be useful to this extent.

Purpose of review: The purpose of this review is to characterize the combined effects of tobacco smoking and human immunodeficiency virus (HIV) infection in people with HIV (PWH) and identify possible therapeutic targets through shared mechanisms for neurotoxicity.

Recent findings: HIV and tobacco smoke can exert neurotoxicity through shared mechanisms such as brain volume changes, microglial dysregulation, and dysregulation of the cholinergic anti-inflammatory pathway (CAP) through the alpha7-nicotinic acetylcholine receptor (nAChR). Evidence also suggests the potential for synergistic effects of HIV and tobacco smoking on neurotoxicity. People with HIV (PWH) are disproportionately affected by both neurocognitive impairment (NCI) and tobacco smoking compared to the general population. Both HIV and tobacco smoking are known to have neurotoxic effects and have the potential for clinically significant impacts on brain health and cognitive functioning. Less, however, is known about how PWH may be uniquely affected by the interactive neurotoxic effects of both HIV and tobacco smoking. Evidence suggests that smoking and HIV can have synergistic effects on neurotoxicity and NCI in PWH. Some mechanisms for neurotoxicity include increased oxidative stress from microglial activation and dysfunction in the alpha7- nAChR cholinergic anti-inflammatory pathway leading to increased neuroinflammation and neuronal apoptosis. Mechanisms may vary by cell type and brain region, however, and there is a need for more human-facing, longitudinal studies on smoking in PWH.