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Objective: This study evaluated the efficacy (day 8) and safety (week 49) of doravirine/islatravir (DOR/ISL; 100 mg/0.75 mg) plus baseline antiretroviral therapy (ART) and optimized background therapy (OBT) in heavily treatment-experienced (HTE) adults living with detectable HIV-1 RNA.

Design and methods: HTE adults with confirmed plasma viral load more than 500 copies/ml receiving a stable ART regimen for at least 3 months were randomly assigned 1 : 2 : 1 : 1 to receive once-daily ISL alone, DOR alone, DOR/ISL, or matching placebo for 7 days; at day 8, baseline ART was optimized and all participants received DOR/ISL and OBT through week 49. The primary efficacy endpoint was percentage of participants receiving DOR/ISL achieving at least 0.5 log 10 decline in viral load from baseline (day 1) to day 8. Secondary efficacy endpoints included HIV-1 RNA levels and CD4 + T-cell counts through week 49.

Results: Thirty-five of the planned 100 participants were enrolled; most were White (57.1%) and men (77.1%) with median age of 50 years. From days 1 to 8, an at least 1.0 log 10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0 in the placebo group. At week 49, HIV-1 RNA less than 50 copies/ml was achieved in 22 participants (71%) and the mean increase in CD4 + T-cell count was 87 cells/μl. Adverse events were reported in 29 participants (82.9%) through week 49; 9 (25.7%) were considered related to DOR/ISL.

Conclusion: DOR/ISL plus OBT improved HIV-1 suppression in HTE adults living with HIV-1 and was generally well tolerated.

Clinicaltrialsgov: NCT04233216.

Background: In people with HIV (PWH), urine tubular biomarkers have been linked to kidney function decline, but urine concentration variability limits their clinical utility. Plasma biomarkers may offer more stable indicators of kidney tubular health.

Methods: We conducted a case-cohort study of 440 PWH from the Multicenter AIDS Cohort Study (MACS)/Women's Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS). Cases developed rapid kidney function decline [RKFD: ≥30% estimated glomerular filtration rate (eGFR) reduction]. We measured plasma biomarkers of tubular injury [kidney injury molecule-1 (KIM-1)], inflammation [tumor necrosis factor receptor-1 (TNFr1) and tumor necrosis factor receptor-2 (TNFr2)], and synthetic function [uromodulin (UMOD) and epidermal growth factor (EGF)] at baseline and year 2. Associations with RKFD were assessed using multivariable risk regression, adjusting for chronic kidney disease (CKD) and HIV-related risk factors, eGFR, and albuminuria. In a random sub-cohort, linear mixed models evaluated associations with annualized eGFR change.

Results: At baseline, median age was 49 years; 33% were women; 69% were virally suppressed; eGFR was similar in cases vs. noncases (93 vs. 94 ml/min/1.73 m 2 ). Over a median of 4.5 years, 172 RKFD events occurred. Each 1-standard deviation higher baseline KIM-1, TNFr1, TNFr2, UMOD, and EGF level was associated with adjusted relative risks (RR) for RKFD of 1.26 [95% confidence interval (CI): 1.15-1.39], 1.39 (1.24-1.55), 1.40 (1.24-1.57), 0.84 (0.77-0.93), and 0.85 (0.78-0.92), respectively. Findings were similar at year 2 and for 2-year biomarker changes. In joint models, baseline KIM-1, TNFr2, and UMOD remained independently associated with RKFD [RR: 1.19 (1.08-1.31), 1.27 (1.12-1.43), and 0.86 (0.78-0.95)], respectively. No biomarker was associated with annualized eGFR change in the sub-cohort.

Conclusion: In PWH, plasma biomarkers reflecting impaired kidney tubular health were independently associated with RKFD and may be useful prognosticators of adverse kidney outcomes.

Background: Increased risk of infectious morbidity and hospitalization has been reported during infancy among children HIV-exposed uninfected (CHEU) compared to children HIV-unexposed uninfected (CHUU). However, data on risks beyond infancy are limited.

Methods: We enrolled pregnant women with and without HIV from a primary healthcare facility in a lower income area in Cape Town, South Africa (2017-2018). We tracked their children's HIV test results and hospitalizations using routine electronic healthcare data. We previously reported increased rates of infectious-cause hospitalization among CHEU in the first year of life, and now extend the analysis to cover the period from age 1 to less than 5 years. Using random-effects Poisson regression, we calculated adjusted incidence rate ratios (aIRR) for infectious-cause hospitalization among CHEU vs. CHUU, clustered by infant and adjusted for child sex and vaccination status, maternal age and education, and housing type.

Results: Among 446 CHEU and 455 CHUU, 147 admissions occurred from age 1 to less than 5  years; with 59% ( n  = 87) due to infections. All-cause hospitalization occurred in 9.2% of CHEU and 10.5% of CHUU; infectious-cause hospitalization occurred in 6.5% of CHEU and 7.3% of CHUU with crude incidence rates of 2.4 per 100 child-years for both groups [IRR = 1.0; 95% confidence interval (CI) 0.6-1.6]. Adjusted analyses showed no evidence of increased hospitalization among CHEU (aIRR = 0.71; 95% CI 0.36-1.41).

Conclusion: Elevated risk of infectious-cause hospitalization among CHEU did not persist beyond the first year of life. These findings highlight infancy as a key window for targeted interventions, while providing reassurance regarding longer term infectious morbidity risk.

Introduction: Estimating undiagnosed HIV prevalence facilitates planning epidemic responses, and monitoring progress towards UNAIDS and national targets. We undertook a systematic review to identify models used to estimate undiagnosed HIV prevalence in overall populations in high-income low-HIV-prevalence countries and territories to inform model selection in New Zealand.

Methods: We searched Medline, EMBASE, Web of Science, CINAHL and Cochrane Database of Systematic Reviews to 5 March 2025. Two authors independently reviewed studies with conflicts resolved by a third. We assessed study quality against five key characteristics of good modelling practice. We undertook a grey literature search to identify modelling in HIV surveillance or monitoring reports.

Results: We identified 2147 unique citations, with 119 full text studies retrieved and 48 included. Forty-six studies described modelling undiagnosed HIV prevalence in 23 countries and territories, a further two for multiple countries. The most common methods used CD4 + back-calculation, with the ECDC model most frequently used (10 studies), followed by a clinical stage-based back-calculation model, a CD4 + depletion model and the Spectrum CSAVR model (eight, four and three studies, respectively). Almost all studies noted a full mathematical model description, included parameters, validation and uncertainty estimates. Only five articles estimated undiagnosed HIV by ethnicity, but estimates by gender and exposure were common.

Conclusion: CD4 + back-calculation models, notably the online accessible ECDC model, have been most commonly used. These are well suited to surveillance systems like New Zealand's, which collect demographic and exposure details and CD4 + cell counts at HIV diagnosis, but limited exposure group size and seroprevalence information.

This study investigates cerebrospinal fluid (CSF) biomarkers associated with HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH) in Brazil. Among 79 HIV-positive participants and 7 negative controls, elevated levels of inflammatory cytokines and soluble CD14 (sCD14) were found. The sCD14 showed promise as a diagnostic marker, and combined with other proinflammatory markers, may improve early detection and monitoring of HAND.

Background: Cognitive frailty (CF, the simultaneous presence of frailty and cognitive impairment) is recognized as a significant predictor of several adverse health outcomes. The objective of this study was to describe prevalence and risk factors for CF in people with HIV (PWH) >50  years.

Methods: This was a cross-sectional observational study including PWH attending Modena HIV Metabolic Clinic (MHMC). Neurocognitive function was measured with Cogstate battery that comprises six domains. Each individual CogState raw score was transformed into z-score after correction for age and sex. Neurocognitive impairment was defined by total global deficit score >0.5. Frailty was assessed by 37-Item frailty index. Scores <0.25 were considered fit or >0.26 as frail.

Results: A total of 1258 PWH were included, 916 (73%) were males, median age was 58 years, median time since HIV diagnosis was 27 years. The sample was divided into four groups (CF) based on the presence of frailty (F) and cognitive impairment (ICT): F+/ICT+, F+/ICT-, F-/ICT+, F-/ICT-. Age per 5-year increase [odds ratio (OR) = 1.27, confidence interval (CI): 1.02-1.55, P  = 0.022], nadir CD4 + cell count (OR = 0.81, CI: 0.66 - 0.99, P  = 0.042) and polypharmacy (OR = 3.47, CI: 2.00-6.00, P < 0.001) were associated with CF after adjustment for time since HIV diagnosis, multimorbidity, depression and cumulative exposure to dolutegravir.

Conclusion: CF prevalence in PWH >50 years was 6.8% and it is higher than what has been observed in the general population >65 years (1-4.4%). Nadir CD4 + cell count and polypharmacy was associated with CF, suggesting an HIV specific contribution related to the development of this condition.

Background: Healthcare needs of older people with HIV (PWH) are changing given the higher incidence and earlier onset of age-related conditions compared to people without HIV (PWoH). This emphasizes a need for novel prognostic markers that allow identification of earlier stages of functional deterioration and prevent its advancement.

Methods: With this aim, we compared muscular imaging markers (whole-body MRI) and plasma biomarkers (irisin, myostatin, and coenzyme Q10) between PWH ( n  = 50) and PWoH ( n  = 25) aged 50 or older, and their associations with clinical conditions. Spearman's rank correlation coefficient was estimated and presented in correlation matrices for the most relevant groups of study variables with intramuscular fat fraction and plasma biomarkers. The distribution of plasma biomarkers and intramuscular fat fraction values was presented graphically in boxplots as a function of the functional test category. The Wilcoxon rank sum test was performed for comparisons, and P values are presented in tables. Raw and adjusted logistic models were fitted, and the estimated odds ratios are presented in tables. Adjusted variables were age, sex, and HIV status group.

Results: PWH exhibited greater deterioration, including lower autonomy, higher rates of prefrailty/frailty and malnutrition, and reduced bone mineral density. Mild to moderate dependency (Barthel) was observed only in PWH (18.4%), with 50% of PWH at risk of dependency (Barber) compared to 25% in PWoH. Prefrailty (Fried) was more prevalent in PWH (46%) than PWoH (28%), and frailty was exclusive to PWH (14%). PWH also had higher plasma myostatin and lower irisin levels. Lower intramuscular fat content was associated with malnutrition and dependency, while total intramuscular fat was positively correlated with time living with HIV and negatively with CD4 + T-cell count. Higher coenzyme Q10 levels were seen in states of poorer health, particularly frailty [Fried, Short Physical Performance Battery (SPPB)], while higher irisin levels were observed together with frailty (Fried) and dependency (Barthel, Barber). For all adjusted models, HIV status strongly influenced Fried, Barthel, and SPPB functional scores.

Conclusion: These findings underscore the need for further assessment of these biomarkers for their diagnostic and predictive potential in aging-related conditions such as frailty in PWH.