AIDS最新文献

Objective: Primary 48-week analyses of the WISARD trial showed maintenance of virological suppression in most participants with K103N mutation when switched from standard regimens to dolutegravir plus rilpivirine (DTG/RPV). In this proof-of-concept pilot study we evaluate 96-week efficacy and safety of DTG/RPV.

Design: Open-label, parallel, two-arm, randomised trial across 32 sites in seven European countries.

Methods: Treatment-experienced HIV-1 participants with HIV RNA <50 copies/mL and documented prior K103N mutation, switched to DTG/RPV either immediately (DTG/RPV-I) or deferred after week 48 (DTG/RPV-D [control]; randomised 2:1). Endpoints were confirmed virological failure (CVF), virological suppression, safety, and changes in patient-reported outcomes from baseline to weeks 48/96.

Results: Of 140 randomised participants (95 DTG/RPV-I, 45 control), 4 had CVF by week 48 (3 DTG/RPV-I, 1 control) and 4 further patients had CVFs by week 96 (2 in each arm). Of the total 8 CVFs through week 96, HIV-1 RNA was ≥400 copies/mL in 4; only one sample amplified with no emergent DTG- or RPV-associated resistance mutations. The other three samples did not amplify due to insufficient sample. The week 96 proportion of subjects with virological suppression was 84.2% for DTG/RPV-I and 73.3% for DTG/RPV-D groups (difference +10.9%, 95% confidence interval -4 to +25.8; p=0.168). Serious adverse events were infrequent in both groups, and none were considered related to study medication. HRQoL, participant satisfaction, and sleep quality were stable over time and similar in both groups.

Conclusions: Week 96 data confirm that switching to DTG/RPV maintains virological suppression and is safe in most participants with a history of K103N.

Background: People with HIV (PWH) remain underrepresented in molecular studies and clinical trials of diffuse large B-cell lymphoma (DLBCL), despite DLBCL being a leading cause of cancer-related death in this population.

Methods: We performed whole-exome sequencing on 30 DLBCL tumors (24 with paired germline) from a Malawian cohort including both HIV-positive (HIV+) and HIV-negative (HIV-) individuals.

Results: KMT2D , BIRC6 , TP53 , and ARID1A were among the most frequently mutated genes. Compared to HIV- DLBCL, the HIV+ DLBCL tumors in this cohort were enriched for mutations in KMT2D , among others, and prior antiretroviral therapy associated with increased tumor mutational burden (TMB) and neoantigen load. Five HIV+ DLBCL tumors exhibited microsatellite instability (MSI), each with strong contributions from mutational signatures related to DNA repair. Furthermore, ARID1A mutations were observed in several MSI samples and in tumors with MSH2 loss. Integration with a published HIV+ DLBCL dataset revealed recurrent driver mutations including LILRB1 p.R30S, MYD88 p.S206C and p.S238N, and NRAS p.Q61K, as well as PTEN mutation as negatively prognostic.

Conclusions: Together, these results highlight distinct tumorigenic mechanisms in HIV+ DLBCL and underscore the need for mutational profiling of HIV+ DLBCL cohorts worldwide to identify biomarkers and therapeutic targets.

Objective: Non-communicable disease (NCD) prevalence has increased as age distributions in populations shift to older ages, including in countries with high HIV burden. We assessed NCD prevalence in Botswana, and its association with human immunodeficiency virus (HIV) and age.

Design: We analyzed cross-sectional data from the Fifth Botswana AIDS Impact Survey 2021, a nationally-representative, population-based survey conducted from March to August 2021.

Methods: People aged 15-64 years old underwent HIV testing and self-reported NCDs. We assessed weighted prevalence and age-stratified logistic regression regarding the associations between HIV status, age, and reported NCDs.

Results: In total, 14,581 respondents were analyzed, of whom 49.2% were male, 20.7% had HIV, 16.4% had ≥1 NCD. People with HIV (PWH) were more likely to be female (64.2% versus 47.3%), 45 years or older (45% vs 17.8%), and report having ≥1 NCD (20.2% vs 15.4%), hypertension (14.2% vs 10.3%), kidney disease (2.6% vs 0.6%), and cancer (1.4% vs 0.3%) compared to people without HIV, respectively. PWH had lower age-adjusted odds of reporting having ≥1 NCD [aOR (95% CI): 0.8 (0.6, 0.9)], diabetes [aOR: 0.6 (0.4, 0.8)], hypertension [aOR: 0.7 (0.6, 0.8)], and heart disease [aOR: 0.6 (0.3, 0.9)]. PWH had higher odds of kidney disease [aOR: 3.2 (2.1, 4.8)] and cancer [aOR: 2.1 (1.3, 3.2)].

Conclusions: : Prevalence of reporting at least one NCD was higher among PWH than the general population but differed by age. Health officials could benefit from considering these trends when designing targeted interventions for PWH.

Objective: To describe Month (M) 24 outcomes following switch to cabotegravir plus rilpivirine long-acting (CAB+RPV LA) in the CARLOS study.

Design: Non-interventional, 3-year, multicenter study.

Methods: M24 effectiveness outcomes included virologic suppression (HIV-1 RNA <50 c/mL), non-response (HIV-1 RNA ≥50 c/mL), and protocol-defined virologic failure (PDVF; two consecutive HIV-1 RNA ≥200 c/mL, or a single HIV-1 RNA ≥200 c/mL followed by treatment discontinuation for any reason). Additional outcomes included dosing window adherence and patient-reported outcomes.

Results: In total, 351 people living with HIV were included in the analysis at M24. Overall, 94% (n = 3464/3676) of CAB+RPV LA injections were administered before or within the ±7-day dosing window; 6% (n = 212/3676) occurred late. At M24, 77% (n = 272/351) of participants maintained virologic suppression, 20% (n = 70/351) discontinued or had no data in window with last observation carried forward <50 c/mL, 0.6% (n = 2/351) had a single HIV-1 RNA ≥50 c/mL, and 2% (n = 7/351) had PDVF. There was a low rate of discontinuation due to injection site reactions. A statistically significant increase in treatment satisfaction total score was observed from baseline to M24 (mean/maximum score [standard deviation], 55.0/66 [10.0]) and 61.0/66 [7.1], respectively; mean change, +6.0; p<0.001; n = 233), meeting the threshold for minimum clinically important difference.

Conclusions: In this real-world study, CAB+RPV LA maintained high rates of virologic suppression, was well tolerated, and led to increased treatment satisfaction through 24 months following switch. These data reinforce the findings of the Phase 3/3b CAB+RPV LA program and support the continued use of CAB+RPV LA in routine clinical care.

Background: Dolutegravir plus lamivudine (DTG+3TC) is a recommended first-line regimen for people with HIV (PWH), based on its efficacy and safety. However, pivotal trials excluded individuals with transmitted resistance-associated mutations (tRAMs), even when these did not affect regimen activity. The impact of such mutations on DTG+3TC efficacy remains unknown.

Methods: This was a preplanned subanalysis of the D2ARLING trial, a randomized, open-label, phase IV study comparing DTG+3TC versus DTG+tenofovir disoproxil fumarate with emtricitabine or lamivudine (DTG+TDF/XTC) in antiretroviral-naïve PWH without baseline resistance test results. Per protocol, baseline genotypic resistance testing was performed on day 1 but remained blinded throughout the study and was only unblinded after completion. Participants with successfully amplified samples were included. The primary endpoint was the proportion with HIV-1 RNA <50 copies/mL at week 48 among those with baseline tRAMs, using both mITT-exposed and observed analyses.

Results: Among 211 participants (DTG+3TC: 104; DTG+TDF/XTC: 107), tRAMs were detected in 24.6%, mainly non-nucleoside reverse transcriptase inhibitors tRAMs. At week 48, viral suppression among participants with tRAMs was achieved in 85.7% (24/28) with DTG+3TC and 91.7% (22/24) with DTG+TDF/XTC (p = 0.67; mITT). In the observed analysis, suppression rates were 96.0% and 95.7%, respectively. Within the DTG+3TC arm, week-48 suppression was 96.0% in participants in whom tRAMs were detected and 98.6% in those without detected tRAMs (p = 0.45). No protocol-defined virological failures occurred in participants with tRAMs receiving DTG+3TC.

Conclusions: DTG/3TC showed high efficacy in participants with tRAMs not affecting this regimen. The detection of such tRAMs did not compromise treatment outcomes in treatment-naïve individuals in this setting.

Objectives: People living with HIV (PLWH) are at increased risk of cerebrovascular abnormalities, including aneurysmal subarachnoid hemorrhage (SAH). However, it is unclear whether HIV-associated inflammation contributes significantly to the inflammatory response observed in the cerebrospinal fluid (CSF) during aneurysm rupture. Here, we used high-throughput Olink proteomics to compare inflammatory marker profiles in CSF between participants with aneurysmal SAH and PLWH without aneurysms.

Design: This was a cross-sectional observational study which enrolled participants who were indicated for endovascular coil embolisation due to ruptured anterior communicating artery aneurysms (n = 30) or who underwent clinically indicated lumbar puncture as part of the workup for non-neurovascular conditions (n = 9).

Methods: We performed a lumbar puncture and analyzed CSF samples from individuals presenting with aneurysmal SAH (n = 30) and PLWH without any known vascular pathology (n = 9). Among the aneurysm patients, 13 were PLWH and 17 were HIV-negative. An Olink Target 96 Inflammation panel was used to quantify inflammatory proteins.

Results: Among 68 detectable inflammatory proteins, 43 were significantly upregulated in participants with aneurysms (n = 30) compared to PLWH without aneurysm (n = 9). A similar inflammatory signature was observed in HIV-negative aneurysm participants (n = 17) and PLWH with aneurysm (n = 13), with no significant differences between these two groups. Interleukin-6 (IL-6) was the most upregulated protein across all aneurysm to non-aneurysm comparisons. These findings suggest that aneurysm rupture is associated with a strong CSF inflammatory response, largely independent of HIV status.

Conclusion: Ruptured intracranial aneurysms are associated with strong upregulation of inflammatory proteins in the CSF. This inflammatory response appears independent of HIV infection.

Objective: To analyze correlates of recent HIV infection among people who inject drugs (PWID) in Ukraine to inform public health interventions.

Design: Secondary data analysis of bio-behavioral surveillance (BBS) studies using respondent-driven sampling (RDS) conducted over multiple years.

Methods: We analyzed data from four rounds of RDS-based BBS conducted among PWID in Ukraine during 2013, 2015, 2017, and 2020. Analysis included 27,852 PWID who participated in 100 RDS studies in 33 cities. Only participants classified as having recent HIV infection and those who tested HIV negative were included. Recent HIV infection was identified using rapid or laboratory recency test, followed by viral load confirmation. We used univariate and multivariable mixed-effect logistic regression models to estimate crude and adjusted odds ratios (aOR) for correlates of recent HIV infection.

Results: The odds of testing recent were greater in 2017 that the other years. Reported use of sterile needles/syringes during the last injection was associated with lower odds (aOR 0.34, 95% CI 0.16-0.73). Having a sex partner living with HIV had the strongest association (aOR 5.58, 95% CI 2.02-15.38) with a recent-positive test result. Recent infections were positively associated with history of incarceration more than one year ago among males (aOR 1.83, 95% CI 1.10-3.06) and among females who were never incarcerated (aOR 2.81 95% CI (1.65-4.77).

Conclusions: This study underscores the importance of sex-specific interventions for PWID. The lower odds of recent HIV in connection to safe injection practices highlights the importance of maintaining sustainable harm reduction programs.