JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: In 2019, a five-year pre-exposure prophylaxis (PrEP) program started in the Netherlands, in which up to 8,500 men who have sex with men (MSM) can obtain PrEP and 3-monthly consultations with HIV/STI testing.

Setting: We assessed the impact of the PrEP program on transmission of HIV and Neisseria gonorrhea (NG) among MSM in the Netherlands and examined prospective variations of the program after 2024.

Methods: We used an agent-based model to estimate the effect of the PrEP program. For prospective PrEP programs from 2024, we varied the capacity (8,500; 12,000; 16,000 participants) and consultation frequency (3-monthly; 6-monthly; 70% 3-monthly and 30% 6-monthly) for t.

Results: At a capacity of 8,500 participants and 3-monthly consultations, the PrEP program could lead to 3,140 (95%CrI 1,780 - 4,780) and 27,930 (95%CrI 14,560 - 46,280) averted HIV and NG infections; requiring 316,050 (95%CrI 314,120 - 317,580) consultations. At a capacity of 16,000 participants the programs with 3-monthly consultations and 6-monthly consultations could lead to comparable numbers of averted HIV (3,940 (95%CrI 2,420 - 5,460), and 3,900 (2,320 - 5,630) respectively) and NG infections (29,970 (95%CrI 15,490 - 50,350), and 29,960 (95%CrI 13,610 - 50,620) respectively), while requiring substantially different numbers of consultations: 589,330 (95%CrI 586,240 - 591,160) and 272,590 (95%CrI 271,770 - 273,290) respectively.

Conclusion: Continuation of a PrEP program could lead to a substantial reduction in HIV and NG transmission. More infections could be averted if the number of participants is increased. In turn, the consultations frequency could be reduced without reducing the number of averted infections if capacity is increased.

Background: Failures in prior roll-out of HIV prevention efforts have widened disparities in HIV incidence by race/ethnicity among young sexual minoritized men (YSMM). We hypothesized greater perceptions of medical mistrust would be associated with lower willingness to get an HIV vaccine, mediating the relationship between race/ethnicity and willingness to accept a future HIV vaccine.

Methods: HIV-negative and unknown-status YSMM 17-24 years old (n = 229) recruited via social media and men-for-men networking apps completed online surveys from September 2021 to March 2022. Participants were asked about demographics, medical mistrust (healthcare-related sexual orientation stigma, healthcare-related race stigma, global medical mistrust, and trust in healthcare providers), and willingness to accept a future HIV vaccine.

Results: Vaccine willingness was highest among White YSMM (96.0%) and lower among Black (71.0%), Latino (83.6%), and multiracial or another race/ethnicity YSMM (80.0%). Even after accounting for medical mistrust constructs as mediators, compared to White participants, Black participants had lower odds of being willing to accept a future HIV vaccine. Participants with greater trust in healthcare providers had higher odds of willingness to accept a future HIV vaccine.

Discussion: Gaps in willingness to get an HIV vaccine are evident among YSMM by race/ethnicity, indicating potential further widening of disparities in HIV incidence when a vaccine becomes available without intervention.

Background: Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TAHOD) and Australia (AHOD).

Methods: People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analysed using repeated measure linear regression. Survival after 10 years was analysed using competing risk regression.

Results: There were 7139 people included: 4867 (68%) from TAHOD and 2272 (32%) from AHOD. Higher CD4 after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101-200: difference=35, 95%CI 18, 51; >200: difference=125, 95%CI 107, 142) compared to ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL which subsequently decreased to <500 (difference=225, 95%CI 213, 236); or those who achieved and maintained CD4 ≥500 cells/µL (difference=402, 95%CI 384, 420), compared to always <500 in the previous decade. Prior protease inhibitor (PI) -based regimen (difference=-17, 95%CI -33, -1) compared to no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = -38, 95%CI -62, -15; and difference=-44, 95%CI -61, -27, respectively) compared to no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (sub-hazard ratio=1.34, 95%CI 1.04, 1.71).

Conclusions: Sustaining high CD4 levels and minimising TI has far-reaching benefits well beyond the first decade of ART.

Background: The relationship between HIV and frailty, a predictor of poor outcomes in the face of stressors, remains unknown in older people in sub-Saharan Africa.

Methods: We analysed data from the Quality of Life and Ageing with HIV in Rural Uganda cohort study to estimate the prevalence and correlates of frailty among older people with HIV (PWH) on long-term antiretroviral therapy and among age and sex-similar HIV-uninfected comparators. Frailty was defined as a self-report of 3 or 4 (and pre-frailty as 1 or 2) of the following phenotypic variables: weight loss, exhaustion, low activity, and slowness. We estimated the prevalence of frailty and pre-frailty and fitted logistic regression models to estimate the association between HIV and frailty, adjusting for sociodemographic factors, depression, and other comorbidities.

Results: We enrolled 599 participants (49% women) with a mean age of 58 years. PWH had a similar prevalence of frailty (8.1% vs. 10.9%, p=0.24) but a lower prevalence of pre-frailty (54.2% vs. 63.2%, p=0.03) compared with their HIV-uninfected comparators. In multivariable regression models, people with depression (AOR 7.52 [95% CI: 3.67-15.40], p<0.001) and those with ≥1 comorbidities (AOR 3.15 [95% CI: 1.71-3.82], p<0.001) were more likely to be frail. HIV serostatus was not significantly associated with frailty (AOR 0.71 [95% CI: 0.37-1.34], p=0.29).

Conclusion: Older PWH had a similar prevalence of frailty as those without HIV. These findings call for additional study of the factors that contribute to the robustness of older PWH in sub-Saharan Africa.

Background: The Visitect CD4 Advanced Disease test (AccuBio, Alva, United Kingdom) is a rapid, semi-quantitative assay that estimates CD4 results above or below 200 cells/μL. We evaluated the performance of the Visitect CD4 assay in semi-urban laboratories in Uganda.

Methods: We performed a pragmatic laboratory validation of the Visitect CD4 platform in four routine HIV clinics in Uganda, nested within a cluster randomized trial evaluating an enhanced package of screening and treatment for persons with advanced HIV disease (NCT05085171). As part of the clinical trial, samples processed on the Visitect CD4 platform were confirmed using another CD4 testing method. We compared the diagnostic performance of the Visitect CD4 platform against the confirmatory method by evaluating the sensitivity, specificity, positive and negative predictive values.

Results: Of 1495 venous blood samples that were processed both by the Visitect CD4 test and another confirmatory CD4 platform at clinics in Kampala, Uganda, specificity was 81% (95% CI, 79%-84%) and the positive predictive value was 69% (95% CI, 66%-73%). There were no samples for which the Visitect test was >200 cells/μL and the confirmatory test was ≤200 cells/μL, resulting in a sensitivity of 100%. Among Visitect CD4 tests that were read as <200 cells/μL with confirmatory results >200 cells/μL, the median confirmatory CD4 result was 397 (IQR, 281-590) cells/μL. Specificity varied by clinic ranging from 63% to 99%.

Conclusions: Given variable specificity of the Visitect CD4 Advanced Disease platform, successful implementation will require consideration of clinic context and laboratory staffing.

Background: Universal antiretroviral therapy (ART) has led to improved treatment outcomes in persons living with HIV. Adherence to ART is required to achieve viral suppression. Real-time medication monitoring (RTMM)-based digital adherence tools (DATs) could be effective in improving ART adherence and viral suppression in persons living with HIV.

Objectives: The primary and secondary objectives of this review were to assess the effect of RTMM-based DATs on improving ART adherence and viral load suppression.

Methods: We searched MEDLINE, Embase, and Global Health for publications published through October 11, 2022. Narrative synthesis and random effects meta-analyses were conducted to synthesize the results.

Results: Of 638 papers identified, 8 were included. Six studies were randomized controlled trials (RCTs), and 2 were cohort studies. Two studies, an RCT in China (mean adherence: 96.2% vs 89.1%) and a crossover cohort study in Uganda (mean adherence: 84% vs 93%), demonstrated improved ART adherence. No studies demonstrated improved viral suppression. In the meta-analyses, we estimated that RTMM-based digital adherence tools had a statistically insignificant small positive effect on ART adherence and viral suppression with a standardized mean difference of 0.1922 [95% CI: -0.0268 to 0.4112, P-value: 0.0854] and viral suppression with an odds ratio of 1.3148 [95% CI: 0.9199 to 1.8791, P-value: 0.1331].

Conclusions: Our meta-analyses found that RTMM-based DATs did not have a significant effect on ART adherence and viral suppression. However, due to few published studies available, heterogeneity of target populations, intervention designs, and adherence measurement instruments, more data are required to provide conclusive evidence.

Introduction: Kaposi sarcoma (KS) is an angioproliferative disease caused by human herpesvirus 8 (HHV-8) and is mediated by cytokines in an immunodeficient environment. This study aimed to compare IL-6, IL-10, and TNFα levels among AIDS patients with disseminated KS (DKS), treatment naïve patients living with HIV (PLWHIV) without DKS, and healthy controls. Secondary outcomes were to compare cytokines levels in patients with DKS and unfavorable outcomes, as well as an analysis of the behavior of cytokines over time.

Methods: This cohort study was performed at two centers in Mexico City. Three groups were included. Group 1: HIV+ treatment naïve with DKS, Group 2: HIV+ treatment naïve without KS, and Group 3: HIV negative, healthy controls. Plasmatic IL-6, IL-10, and TNFα levels were measured at baseline and over time in Groups 1 and 2.

Results: Seventy-six patients were included: 39 (52%) in Group 1, 17 (22%) in Group 2, and 20 (26%) in Group 3. The median baseline IL-6, IL-10, and TNFα levels were significantly higher in group 1. In group 1, baseline IL-6 was higher in patients who died than in survivors (14.4 vs 5.8 pg/mL p=0.048). Patients with severe immune reconstitution inflammatory syndrome due to KS (S-IRIS-KS) had higher IL-6 values than those without it (14.4 vs 5.8 pg/mL p=0.004). In the repeated-measures model in group 1, IL-10 levels were higher in patients who died (p<0.001) and developed IRIS-KS (p=0.01).

Conclusions: IL-6, IL-10, and TNF α levels were markedly higher in patients with DKS. IL-6 and IL-10 levels were higher in patients with unfavorable outcomes.

Background: Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity.

Methods: Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, gender, ethnicity, smoking status, and antiretroviral therapy (ART).

Results: Ninety-nine ART-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and LBP. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation and atherosclerosis pathways were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (aOR 2.7, 95% CI [1.7, 4.29]), IL-6 (3.77 [1.43, 9.93]), vWF (5.33 [1.51, 18.75]), E-selectin (6.28 [1.36, 29.04]), MPO (6.85 [1.87, 25.04]), IL-1RA (6.45 [2.28, 18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation.

Conclusions: Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Background: New dosage form and frequency options may improve HIV treatment outcomes and reduce disparities in access and use.

Methods: People with HIV (PWH) in the US completed a demographic and discrete choice experiment survey of preference for 13 hypothetical HIV treatment options: daily and weekly oral tablets; 1-, 3-, or 6-monthly injections by self or a health care provider; yearly implant; or combinations. Best-worst scaling and a latent class model were used to analyze overall preference choices and for groups of individuals with similar patterns of preferences; the model also predicted uptake of products.

Results: Among the diverse 829 respondents, weekly oral tablets and 6-monthly injections by an HCP were significantly more favored than daily oral tablets. Convenience of the treatment and being tired of taking pills were the top drivers of preference responses. Latent class analysis identified four groups of respondents with distinct preference patterns; approximately two-thirds belonged to groups strongly preferring products other than daily oral tablets. The modelled uptake of a monthly pill, yearly implant, 6-monthly Health Care Provider (HCP) injection, oral daily pill, and 3-monthly HCP injection were 24%, 24%, 24%, 18%, and 11%, respectively.

Conclusions: Patterns of HIV medication preference can inform development of new forms of HIV therapy products as the majority of patients do not prefer the currently most available treatment option of daily oral tablets. Looking beyond population-level preferences and into similar groups of PWH increases the ability to develop patient-centered products to fill gaps in care and increase treatment effectiveness.