AIDS research and human retroviruses最新文献

HIV RNA plasma viral load (VL) is the standard surrogate marker to monitor response to antiretroviral treatment (ART). We compared the linearity, repeatability, and concordance of six commercially available HIV RNA VL platforms using clinical samples from patients from Brazilian sites where different HIV-1 subtypes co-circulate. A total of 150 plasma samples from each city were collected in Curitiba, Southern Brazil (subtype C), São Paulo (subtype B), and Santos (BF recombinants), Southeast Brazil. Platforms were VERSANT^® Siemens HIV RNA 1.0 (kPCR); VERSANT^® Siemens HIV-1 RNA 3.0 (bDNA); Abbott Real-Time HIV-1; NucliSens EasyQ^® HIV-1 v2.0 Biomerieux; COBAS^® TaqMan^®, Roche; and artus HIV Virus-1 RT-PCR, QIAGEN. OptiQuant HIV-1 RNA quantification panel was used to compare VL linearity, using samples containing 50, 500,5,000, 50,000, 500,000, and 5,000,000 HIV copies/mL. HIV RNA panels with subtypes A, B, C, D, F, G, H, circulating recombinant form (CRF)1, and CRF2 were utilized. A high degree of linearity and repeatability was demonstrated for all platforms. When compared with a subtype B reference sample, 17 of 54 (31.48%) samples diverged by more than 0.5 log₁₀ copies/mL. Except for the Roche platform, all platforms underestimated subtype C VLs. A total of 743 (82.6%) valid results were obtained with samples from São Paulo, 707 (78.6%) from Santos, and 673 (74.8%) from Curitiba (São Paulo vs. Santos, p = .03; São Paulo vs. Curitiba, p = .00006; Santos vs. Curitiba, p = .06). The number of discordant samples between different methodologies when VL was undetectable in one method and detectable in the other ranged from 1.25% (Abbot vs. Siemens) to 44.8% (Abbott vs. Biomerieux). Finding samples with undetectable VL in one method and a high VL in another might have important individual and public health consequences. Standardization of VL measurements, particularly for non-B subtypes infections, especially subtype C, is necessary to maximize the individual and public health benefits of ART globally.

Central memory (T_CM) cells are a subpopulation of CD4 T cells that sustain overall CD4 T cell counts in HIV infection. The mechanisms underlying their eventual demise, which leads to loss of CD4 T cell counts, are not known. To understand their proneness to death despite their increased movement to proliferation, we examined cell division together with possible cell accumulation in different phases of the cell cycle. Purified circulating T_CM cells from untreated people living with HIV (PLWH) (n = 9) and healthy controls (n = 10) were stimulated in vitro using anti-CD3/CD28 agonistic antibodies plus IL-2 and cultured for 4 days. Cell viability, DNA content, proliferation, and cyclin A and cyclin B expression were measured. We found that PLWH T_CM cells more frequently had a DNA content lower than G0/G1, compared with controls (p = .043). These cells accumulated with each division. The proportion of cells with sub-G0/G1 DNA content that were cycling (expressing cyclin A) was greater in the PLWH group (p = .003). The percentage of T_CM cells expressing cyclin A+ among those in G0/G1 and was also greater in the PLWH group (p = .043), suggesting arrest before G2/M. While T_CM cells from PLWH can proliferate, during this process some of them accumulate defects in DNA content that are incompatible with viability, suggesting that they could be intrinsically prone to cell cycle-dependent death. This provides a possible mechanism underlying the increased T_CM cell turnover in HIV infection.

Only one study to date has focused on people living with HIV (PLWH) who refused to participate in a HIV cure/remission-related clinical trial (HCCT)-"decliners" hereafter-that included analytical treatment interruption (ATI). Exploring why these persons refuse may provide valuable information to ensure more ethical recruitment and support in HCCTs within the bigger picture of improving HIV cure research. The qualitative component of the AMEP-EHVA-T02/ANRS-95052 study, called AMEP-Decliners, documented the experiences of French PLWH who refused to participate in EHVA-T02/ANRS-VRI07, a phase II randomized, placebo-controlled HCCT with ATI. AMEP-Decliners comprised semi-structured individual interviews with six decliners in two HIV care sites in France between September 2022 and March 2023. The interviews documented their expectations regarding HCCTs, reasons for refusal, and perceived factors that might have led them to participate. Audio files were transcribed, and an inductive thematic analysis was performed. Surprisingly, the main reason for refusal was not ATI but the trial monitoring. Besides the frequency of appointments, respondents emphasized the incompatibility with their active life. One underlying reason for refusal was that participating would have meant "break[ing] the carefree attitude about the disease," reflecting the substantial psychological burden associated with participation. Finally, respondents perceived that the trial's clinical team did not sufficiently recognize their "normal life" and the level of commitment required to participate, leading them to call for greater involvement by the team: "they have to make an effort too." Results from decliners' discourses highlighted that two levels of commitment to participation must be considered when developing HCCTs: psychological burden and logistical constraints. We suggest allowing home examinations and flexible appointment times, prioritizing face-to-face invitations in order to address the psychological burden associated with HCCT participation, and explaining the reasons for monitoring constraints when they cannot be alleviated. Further studies are necessary to confirm our results.

Heterosexuals have become the most prevalent group of HIV-1 in Kunming, Yunnan Province. Utilizing the principle of genetic similarity between their gene sequences, we built a molecular transmission network by gathering data from earlier molecular epidemiological studies. This allowed us to analyze the epidemiological features of this group and offer fresh concepts and approaches for the prevention and management of HIV-1 epidemics. Cytoscope was used to visualize and characterize the network following the processing of the sample gene sequences by BioEdit and HyPhy. The number of possible links and the size of the clusters were investigated as influencing factors using a zero-inflated Poisson model and a logistic regression model, respectively. A scikit-learn-based prediction model was developed to account for the dynamic changes in the HIV-1 molecular network. Six noteworthy modular clusters with network scores ranging from 4 to 9 were found from 150 clusters using Molecular Complex Detection analysis at a standard genetic distance threshold of 0.01. The size of the number of possible links and the network's clustering rate were significantly impacted by sampling time, marital status, and CD4⁺ T lymphocytes (all p < 0.05). The gradient boosting machine (GBM) model had the highest area under the curve value, 0.884 ± 0.051, according to scikit-learn. Though not all cluster subtypes grew equally, the network clusters were relatively specific and aggregated. The largest local transmission-risk group for HIV-1CRF08_BC is now the heterosexual transmission population. The most suitable model for constructing the HIV-1 molecular network dynamics prediction model was found to be the GBM model.

Data on persons with perinatally acquired HIV infection in the Caribbean are limited; thus, a chart review was conducted among these clients at an adult HIV treatment clinic in Trinidad over the period January 01, 2011-June 30, 2023. Sociodemographic, clinical, and laboratory data were extracted and analyzed using RStudio version 2021.09.0. Fifty-four study participants were followed up, age range 18-29 years, and there were 27 (50%) males. Eighteen participants (33.3%) were institutionalized until the age of 18 years, while 36 (66.7%) lived with caregivers/relatives and attended outpatient pediatric clinic. The transition from the sheltered environment of pediatric care to the adult HIV clinic was turbulent for some participants as they experienced HIV-related stigma, which may result in poor HIV outcomes. At the initial clinic visit, 28 (51.9%) study participants were virally suppressed (HIV viral load <1,000 copies/mL), which included 12 (66.7%) of 18 who were institutionalized as compared to 16 (44.4%) of 38 who lived with caregivers/relatives (p = 0.387). Data from their last clinic visit showed 31 (57.4%) participants were virally suppressed; 13 (24.1%) were lost to follow-up from care, and there were 6 (11.1%) deaths; 29 (53.7%) were on antiretroviral therapy single-tablet regimens (STRs) and 25 (46.3%) on complex multiple-tablet regimens (MTRs). Institutionalized clients and those on STRs were more likely to be virally suppressed than those living with relatives (p = 0.043) and those on MTR (p < 0.001), respectively. Reported deaths were higher among clients who lived with caregivers/relatives and those on MTR. Participants of younger age were less likely to achieve viral suppression (p = 0.02). Comprehensive programs that include STRs, the engagement of caregivers/relatives and health workers, life skills, and enhanced psychosocial interventions for youths living with perinatally acquired HIV are important to support the transition to adult care and reduce the complex challenges of living with a stigmatizing disease.

Climate change poses one of the most significant modern threats to overall human health,especially for vulnerable populations including persons living with HIV (PLWH). In this perspective, we specifically explore the concept of immune resilience in human health and how climate change phenomena - including extreme weather events, food insecurity, pollution, and emerging diseases - may exacerbate immune dysfunction and comorbidities faced by PLWH and hinder access to HIV treatment and prevention services. Multidisciplinary, collaborative efforts are urgently needed to quantify these impacts, develop mitigation strategies, and strengthen policies and funding to bolster immune resilience for PLWH in the face of accelerating climate change.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4⁺ cell count was 1,235 cells/mm³ [n = 51] at baseline, 1,690 cells/mm³ (n = 41) at Week 48, and 1,280 cells/mm³ (n = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.

Mother-to-child transmission (MTCT) of HIV-1 and associated mortality continue to occur at unacceptably high rates, despite the extensive rollout and implementation of Prevention of Mother-to-Child Transmission (PMTCT) Programs, including the modified versions of Option B and B+ in 2010 and 2012, respectively. Maternal HIV viral load (VL) and socio-behavioral factors sustaining MTCT in Rwanda remain largely unexplored. The study examined the effects of socio-behavioral factors on maternal VL and their contribution to in utero transmission of HIV-1 in the context of Rwanda's HIV epidemic. A prospective cohort study was conducted in 862 mother-baby pairs enrolled in 10 PMTCT clinics in Rwanda. VL was determined on plasma and Dried Blood Spots samples, whereas HIV DNA PCR was performed to determine in utero MTCT of HIV of the babies immediately at birth and then at 3 weeks, 4 weeks, 6 months, and 18 months, together with HIV antibody testing to determine other forms of MTCT of HIV. Quantitative data on socio-behavioral factors were collected through a structured questionnaire. Linear regression and univariate analysis of variances using SPSS 25.0 were used to test the hypotheses. We found 22/862 (2.55%) cases of in utero transmission and a total of 32/862 (3.7%) cases of MTCT of HIV-1 over 18 study months. Maternal VL at delivery was significantly associated with the risk of in utero transmission of HIV-1. Socio-behavioral factors associated with elevated maternal VL at delivery included alcohol, smoking, multiple sexual partners, mothers' income, being a casual laborer, and distance to health care services. We report an MTCT rate of 3.7% in our study population over the 18 months, higher than the national average of 1.5%, the majority of which occurred in utero. MTCT cases were attributable to failure to suppress maternal VL.

To improve current and future use of existing (oral, injectable) and potential future (implants, douches) pre-exposure prophylaxis (PrEP) products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the United States, South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches. Next, they completed a choice exercise in which they were shown 10 screens, each presenting 3 of the aforementioned products at a time with 11 attributes for physicians and 10 attributes for GBM. For the attributes that were not constant, one level was shown per screen for each product. Participants selected the product they preferred most and rated their likelihood to select (GBM) or recommend (physicians) that product. Data were modeled using hierarchical Bayes estimation; resulting model coefficients were used to develop attribute importance measures and product preferences. For GBM across all countries, if all aforementioned PrEP products were on the market at the same time, over 90% of GBM would use some form of PrEP; 100% of physicians would recommend at least one of the PrEP products. There were variations in product preference by country. GBM in the United States and Thailand preferred the injection (21.7%, 22.9%, respectively), while the dissolvable implant was preferred in South Africa and Spain (19.9%, 19.8%, respectively). In the United States, South Africa, and Spain (where physician data were available), physicians were most likely to recommend the dissolvable implant (37.2%, 40.6%, 38.3%, respectively).

Functional magnetic resonance imaging (fMRI) studies have demonstrated that HIV-infection affects the fronto-striatal network. It has not been examined what impact efavirenz (EFV), an antiretroviral drug notorious for its neurocognitive effects, has on the reward system: a key subcomponent involved in depressive and apathy symptoms. Therefore, this study aims to investigate the effect of EFV on reward processing using a monetary incentive delay (MID) task. In this multicenter randomized controlled trial, asymptomatic adult participants stable on emtricitabine/tenofovirdisoproxil fumarate (FTC/TDF)/EFV were randomly assigned in a 2:1 ratio to switch to FTC/TDF/rilpivirine (RPV) (n = 30) or continue taking FTC/TDF/EFV (n = 13). At baseline and 12 weeks after therapy switch, both groups performed an MID task. Behavior and functional brain activity related to reward anticipation and reward outcome were assessed with blood-oxygen-level-dependent fMRI. Both groups were matched for age, education level, and time since HIV diagnosis and on EFV. At the behavioral level, both groups had faster response times and better response accuracy during rewarding versus nonrewarding trials, with no improvement resulting from switching FTC/TDF/EFV to FTC/TDF/RPV. No significant change in activation related to reward anticipation in the ventral striatum was found after switching therapy. Both groups had significantly higher activation levels over time, consistent with a potential learning effect. Similar activity related to reward outcome in the orbitofrontal cortex was found. Discontinuing FTC/TDF/EFV was not found to improve activity related to reward anticipation in asymptomatic people living with HIV, with similar cortical functioning during reward outcome processing. It is therefore likely that EFV does not affect motivational control. Further research is needed to determine whether EFV affects motivational control in HIV populations with different characteristics.