AIDS最新文献

Objective: France provides universal health coverage to all residents, including undocumented migrants. Most transgender women with HIV (TWH) in France are migrants from Latin America. This study aimed to describe the rate of viral suppression among TWH in France and identify structural factors influencing this outcome.

Design: Trans&HIV is a French, nationwide, cross-sectional, retrospective life-event survey and community-based research study conducted between August 2020 and June 2022. Community-based interviewers recruited and administered questionnaires to 536 TWH in 36 different HIV care units.

Methods: We calculated the rate of viral suppression in TWH on antiretroviral therapy (ART) for at least 1 year using data from medical records, and identified associated structural factors, adjusting for clinical factors, using Firth's penalized logistic regression.

Results: Of the 506 participants with complete data, 86% were non-French nationals, most (83%) were born in Latin America. Thirty percent of participants were undocumented and 75% did not have gender-concordant identity documents. Eighty-eight percent ( N  = 486) had achieved viral suppression. After adjustment for clinical factors, structural factors negatively associated with viral suppression included a lack of healthcare coverage [aOR = 3.32, 95% confidence interval (95% CI) 1.23-8.66] and not having gender-concordant identity documents [aOR = 2.05, 95% CI (1.00-4.64)]. TWH receiving state medical assistance for undocumented migrants had similar viral suppression levels to those with general public health insurance.

Conclusion: Although TWH in France have a high rate of viral suppression, barriers to comprehensive health and social inclusion persist, particularly access to healthcare coverage and legal recognition of their self-identified gender. Addressing these structural obstacles through inclusive policies is essential to improve health outcomes for this population.

Objective: Dyslipidemia is common in severe infections, but its role in patients with HIV and talaromycosis (PWHT) remains unclear.

Design and methods: Three hundred and eighty-seven PWHT were enrolled in present study. Furthermore, 267 of 387 PWHT, 267 people with HIV but without talaromycosis (PWH), and 267 healthy controls were selected to compare the lipid profiles by propensity score matching (PSM) method on sex, age, body mass index (BMI), comorbidities and hepatitis B virus (HBV) infection.

Results: PWHT showed significantly lower total cholesterol [2.9 (2.2-3.5) vs. 3.5 (2.9-4.0) vs. 4.6 (4.0-5.2) mmol/l, P  < 0.001], LDL [1.5 (0.9-2.0) vs. 1.9 (1.5-2.4) vs. 2.5 (2.1-3.1) mmol/l, P  < 0.001] and HDL [0.5 (0.3-0.7) vs. 0.7 (0.6-0.9) vs. 1.2 (1.0-1.4) mmol/l, P  < 0.001], but higher triglycerides [1.6 (1.2-2.0) vs. 1.3 (1.0-1.7) vs. 1.2 (0.9-1.7) mmol/l, P  < 0.001] than PWH and healthy controls at admission. Multivariate Cox analysis identified triglycerides at least 2 mmol/l [adjusted odds ratio (AOR) (95% confidential interval, CI): 2.5 (1.3-4.7), P  = 0.005], HDL less than 0.3 mmol/l [AOR:2.7 (1.4-5.3), P  = 0.004], age at least 35 years [AOR:3.2 (1.6-6.4), P  = 0.001], BMI less than 18.0 kg/m 2 [AOR:2.0 (1.0-3.8), P  = 0.036), WBC at least 5 × 10 9 /l [AOR:2.4 (1.3-4.6), P  = 0.006], albumin less than 27 g/l [AOR: 2.7 (1.2-6.3), P  = 0.018], and nonamphotericin B therapy [AOR: 2.2 (1.1-4.5), P  = 0.028] as independent mortality risk factors. The 30-day overall mortality was higher in patients with triglycerides at least 2 mmol/l (24.0 vs. 7.6%, Log-rank P  < 0.001) or HDL less than 0.3 mmol/l (27.1 vs. 6.5%, Log-rank P < 0.001) among PWHT.

Conclusion: PWHT exhibited distinct dyslipidemia patterns from PWH and healthy control. Elevated triglycerides and reduced HDL independently predicted poor outcomes of PWHT.

Objective: Food insecurity is a risk factor for metabolic dysfunction-associated steatotic liver disease in the general population. However, little is known about the impact of food insecurity on hepatic steatosis among women with HIV (WWH) and women without HIV (WWOH).

Design: We assessed hepatic steatosis by controlled attenuated parameter (CAP) in decibels/meter (dB/m) and food security status using the U.S. Household Food Security Survey in women without viral hepatitis. Women were categorized as being food secure vs. food insecure.

Methods: We performed multivariable linear regression analyses to examine the association of food security status with hepatic steatosis.

Results: Among 1473 women (1064 WWH, 409 WWOH), 20% reported food insecurity. Food insecurity was associated with lower CAP after adjustment for age, race-ethnicity, income, alcohol intake, BMI, insulin resistance, and HIV [CAP difference: -8.6 dB/m, 95% confidence interval (95% CI): -16.7 to -0.5, P  = 0.037]. Each 5 kg/m 2 BMI increase was associated with an 18.4 dB/m CAP increase (95% CI: 16.4-20.3, P  < 0.001); there was no association of HIV serostatus with steatosis. Additionally, there was a significant interaction between food insecurity and BMI: among women experiencing food insecurity, for every 5 kg/m 2 BMI increase, CAP decreased by 6.6 dB/m (95% CI: -12.2 to -1.1, P  = 0.02).

Conclusion: Food insecurity is prevalent in WWH and, unexpectedly, is associated with less steatosis, in contrast with findings observed in the general population. Additionally, while obesity remains a strong driver of steatosis, food insecurity attenuates the association of BMI with steatosis, particularly at higher BMIs. This study lays the groundwork for future efforts exploring potential mechanistic pathways.

Africa is home to the majority of people with HIV (PWH) worldwide. Improved availability and access to antiretroviral treatment (ART) has improved survival, resulting in an ageing population now facing long-term HIV-associated morbidity, including musculoskeletal conditions. There is growing evidence on the impact of chronic HIV infection and ART on muscle and bone health. Musculoskeletal complications among PWH increase the risk of injury, disability, pain, reduces quality of life, and incurs substantive healthcare and economic costs. This review discusses mechanisms by which HIV may affect bone and muscle, including direct cellular stress, indirect chronic inflammation, immunosenescence and hormonal dysregulation, as well as ART-related effects. It appraises evidence for bone and muscle health among PWH across different age groups and populations in Africa. Potential interventions such as improved nutrition, physical activity, vitamin D and calcium supplementation, and use of bisphosphonates to attenuate musculoskeletal morbidity are discussed. Musculoskeletal health services need to be integrated into core HIV-care services. Routine fracture risk assessments and robust preventive management strategies should become the norm, to reduce musculoskeletal morbidity among PWH in Africa.

Objective: Lopinavir/ritonavir (LPV/r) remains a much used drug combination for treatment of children with HIV, but pharmacokinetic data when the adult formulation (LPV/r 200/50 mg) is used for children weighing 25-34.9 kg, or when combined with tenofovir alafenamide/emtricitabine (TAF/FTC), is currently lacking.

Design: We aim to provide this data by an intensive LPV/r pharmacokinetic sub-study nested within the CHAPAS-4 trial (#ISRCTN22964075).

Methods: Children (3-15 years), weighing 14-24.9 kg received 200/50 mg LPV/r orally twice daily; those weighing 25-34.9 kg received 400/100 mg LPV/r in the morning and 200/50 mg in the evening; and those weighing at least 35 kg received 400/100 mg LPV/r twice daily. LPV/r was used in combination with either TAF/FTC or standard-of-care backbone (abacavir/lamivudine or zidovudine/lamivudine). Pharmacokinetic parameters were compared to those reported in children receiving WHO-recommended dosages.

Results: We enrolled 40 children from Uganda, Zambia, and Zimbabwe. The geometric mean area under the concentration-time curve (AUC 0-12h ) for LPV was 116.2 h mg/l [coefficient of variation (CV%), 37%], comparable to children receiving WHO-recommended dosages. The geometric mean trough concentration was 7.7 mg/l (52%), 57% higher than the reference value of 4.9 mg/l (95% confidence interval, 4.14-5.80), mainly caused by higher exposure in children 25-34.9 kg. There were no differences in LPV AUC 0-12h or Ctrough between backbones.

Conclusion: Children (3-15 years), weighing at least 14 kg and taking LPV/r in second-line treatment achieve adequate exposure of LPV within limits reported to be safe and well tolerated. These data support the use of a LPV/r-based regimen and the adult formulation of 200/50 mg in children 25-34.9 kg.

Objective: Government-imposed physical distancing restrictions during the COVID-19 pandemic disrupted biobehavioral HIV prevention practices and access to healthcare services. This study aimed to use a mathematical model to evaluate the impact of COVID-19 on the HIV epidemic among MSM in Australia, using empirical data.

Design: A retrospective modeling study.

Methods: We developed a mathematical model to estimate monthly HIV incidence between January 2020 and August 2022. We obtained aggregated monthly data for sexual partners, condom use, HIV testing, preexposure prophylaxis (PrEP) use, and migration. Three scenarios were simulated: a COVID-19 scenario; a no COVID-19 scenario where input parameters remained at pre-COVID-19 values; and a no COVID-19 scenario with continued PrEP scale-up.

Results: In the absence of the COVID-19 pandemic, 1263 (95% percentile interval: 880-1706) infections would have occurred between January 2020 and August 2022 compared to 915 (95% percentile interval: 638-1282) for the COVID-19 scenario (a 27.6% reduction). Reduced sexual partners was the leading factor contributing to the change in HIV infections and diagnoses (-24.9 and -10.6%, respectively). MSM aged at least 50 years had a larger reduction (31.0%) in new HIV infections than their younger counterparts (19.9%).

Conclusion: A substantial reduction in new HIV infections and diagnoses in Australia occurred during the COVID-19 pandemic, largely due to decreased numbers of sexual partners. This reduction underscores the need for sustained public health strategies leveraging reduced transmission rates to continue progress toward eliminating HIV in Australia.

Background: Despite effective antiretroviral therapy (ART), residual low-level HIV viremia may persist. Integrase inhibitor (INSTI)-based regimens have become preferred treatments, but their impact on controlling residual viral replication remains unclear.

Objective: To evaluate the impact of integrase inhibitor-based regimens on achieving target not detected (TND) rates compared to other antiretroviral strategies.

Methods: This retrospective cohort study assessed 131 virologically suppressed people with HIV (PWH) categorized into four treatment groups: Group 1, treated with protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimens ( n  = 30); Group 2, treated with INSTI-based regimens ( n  = 30); Group 3, initially treated with protease inhibitor/NNRTI regimens who switched to INSTI-based therapy ( n  = 26); and Group 4, initially treated with INSTI triple therapy who switched to dual therapy ( n  = 30). The primary endpoint was the proportion of "target not detected" (TND) HIV-1 RNA measurements.

Results: INSTI-based regimens showed significantly higher TND rates compared to PI/NNRTI-therapies (difference: 18.5%, P  < 0.001). Switching from PI/NNRTI to INSTI-based therapies increased TND rates from 52.6 to 92%. Multivariate analysis identified shorter time to viral suppression and absence of HCV co-infection as factors associated with higher TND rates. No significant differences were observed when switching from INSTI-based triple therapy to INSTI-based dual therapy.

Conclusion: INSTI-based regimens, whether triple or dual therapy, achieve better control of residual viremia compared to other treatment strategies. This improved virological control was maintained during follow-up and was independent of the number of drugs.

Background: Weight gain is common in treatment naïve people with HIV (PWH) initiating antiretroviral therapy (ART). The mechanisms driving this weight gain are unclear. The current study tested the hypothesis that bone-derived hormones are associated with weight gain with ART initiation and that the associations are antiretroviral (ARV) specific.

Methods: Plasma samples were obtained from the Advancing Clinical Therapeutics Globally (ACTG) study A5260s, in which treatment naïve PWH were initiated on tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) plus either atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Plasma levels of bone-derived hormones, undercarboxylated osteocalcin (ucOCN), lipocalin-2 (NGAL), and sclerostin and body weight were measured at baseline and 48-weeks after ART initiation. The associations between change in bone-derived hormones and weight with ART initiation were assessed using linear regression models adjusted for age, sex, race, baseline viral load, and CD4 + cell count change.

Results: Increases in ucOCN and decreases in NGAL were associated with weight change in PWH initiating ART. Sclerostin was not associated with weight change. When assessed as a function of ART, both ucOCN and NGAL were associated with weight for participants initiating RAL-based ART, but not ATV/r or DRV/r. After adjustment, the association between ucOCN and weight was no longer significant, while the association with NGAL remained statistically significant in RAL recipients.

Conclusions: This study suggests links between bone-derived hormones and ART induced weight gain in PWH and demonstrates that this relationship is influenced by specific antiretrovirals.

Objective: We investigated how randomness may have contributed to the apparent decline in observed risk of neural tube defects (NTDs) following in-utero dolutegravir (DTG) exposure. We aimed to describe statistical approaches to uncertainty using accessible language for nonstatistical audiences.

Methods: We reanalyzed Tsepamo Study data using frequentist confidence intervals, repeated intervals accounting for group sequential monitoring, and Bayesian posterior and posterior predictive distributions. We estimated the probability of decision reversal using simulation.

Results: The initial Tsepamo analysis reported a large difference in NTD risk between DTG and non-DTG exposures, with point estimates of 0.94 and 0.12%, respectively. This difference diminished with subsequent data, with updated estimates of 0.10% for DTG and 0.11% for non-DTG exposures. Our analyses showed the early finding was statistically compatible with a wide range of effect sizes, including no difference. Due to the large uncertainty in the first analysis, the probability of decision reversal was high under repeated testing frameworks.

Conclusion: Early safety signals may reflect statistical noise. Evaluating the range of confidence intervals and estimating decision reversal probabilities provide meaningful insight into early results. Formal frameworks for uncertainty should guide decisions about interim data reporting, especially when findings may influence clinical or regulatory action.

Despite the relatively low transmission rates of HIV-1, the virus accounted for 1.5 million new infections in 2020, with widespread infection and devastating sequelae. Various mechanisms have been described, which exacerbate HIV-1 progression, including concurrent infection with other sexually transmitted infections (STIs). Epidemiological evidence has suggested the strongest association between Neisseria gonorrhoeae and HIV-1 compared to other STIs and the presence of untreated N. gonorrhoeae before infection with HIV-1 has been shown to enhance viral infection. Molecular investigation has corroborated this by showing that presence of N. gonorrhoeae enables transmission of HIV-1 across the epithelial membrane, enhances replication of HIV-1, increases viral shedding, and heightens immune dysregulation. Gonorrhoea infections are rapidly increasing worldwide providing a potential platform for increased HIV-1 incidence. Furthermore, whilst treatment of N. gonorrhoeae in parallel infection alleviates HIV-1 progression and transmission, this is becoming a less viable option as the threat of multidrug resistance within N. gonorrhoeae proliferates. These findings highlight the requirement for greater surveillance of concurrent infections to tackle the HIV-1 epidemic and warrant monitoring of the resistance crisis in N. gonorrhoeae to prevent worsening outcomes of HIV-1 patients.