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Background Predicting cause-specific mortality among people with HIV (PWH) could facilitate targeted care to improve survival. We assessed discrimination of the Veterans Aging Cohort Study (VACS) Index 2.0 in predicting cause-specific mortality among PWH on antiretroviral therapy (ART). Methods Using Antiretroviral Therapy Cohort Collaboration data for PWH who initiated ART between 2000 and 2018, VACS Index 2.0 scores (higher scores indicate worse prognosis) were calculated around a randomly selected visit date at least 1 year after ART initiation. Missingness in VACS Index 2.0 variables was addressed through multiple imputation. Cox models estimated associations between VACS Index 2.0 and causes of death, with discrimination evaluated using Harrell's C-statistic. Absolute mortality risk was modelled using flexible parametric survival models. Results Of 59 741 PWH (mean age: 43 years; 80% male), the mean VACS Index 2.0 at baseline was 41 (range: 0–129). For 2425 deaths over 168 162 person-years follow-up (median: 2.6 years/person), AIDS (n = 455) and non–AIDS-defining cancers (n = 452) were the most common causes. Predicted 5-year mortality for PWH with a mean VACS Index 2.0 score of 38 at baseline was 1% and approximately doubled for every 10-unit increase. The 5-year all-cause mortality C-statistic was.83. Discrimination with the VACS Index 2.0 was highest for deaths resulting from AIDS (0.91), liver-related (0.91), respiratory-related (0.89), non-AIDS infections (0.87), and non–AIDS-defining cancers (0.83), and lowest for suicides/accidental deaths (0.65). Conclusions For deaths among PWH, discrimination with the VACS Index 2.0 was highest for deaths with measurable physiological causes and was lowest for suicide/accidental deaths. [ABSTRACT FROM AUTHOR]

Introduction While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. Methods Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as 'other.' Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan-Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. Results 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly 'other' a higher risk for discontinuation (Table 1). Availability of more effective/convenient treatment (28.9%) was the main reason for discontinuation, especially in the group 'other' (43.5%), RAL (34.6%) and DRV (31.6%). Non-specified patient or physician wish to modify therapy was revealed in 17.4% and 9.3% respectively. EFV was modified in 52.8% due to central nervous system toxicity and ATV in 27.8% for gastrointestinal toxicity including hyperbilirubinemia. Conclusion Rates of modification and interruption were still high in recent years, particularly in the first year of ART. The decreased rate of modification found in patients treated with Rilpivirine may be attributed to selection of patients according to guidelines. [ABSTRACT FROM AUTHOR]

Introduction For some patients, it remains a challenge to achieve complete virological suppression which is the goal of antiretroviral therapy (ART). Identifying factors associated with low-level viraemia (LLV) and virological failure (VF) under ART might help to optimize management of these patients. Materials and Methods We investigated patients from the Austrian HIV Cohort Study receiving unmodified ART for >6 months with two nucleoside reverse-transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an integrase inhibitor (INSTI) between 1 July 2012 and 1 July 2013 with at least one viral load (VL) measurement below the limit of detection (BLD) or below level of quantification (BLQ) in their treatment history. VF was defined as HIV-RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLD and BLQ were identified by using logistic regression models. Results Of the 2,276 patients analyzed, 1,972 (86.6%) were BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was found in patients with ART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from a centre which uses Abbott RealTime HIV-1 assay compared to the other centres measuring VL by the Roche Cobas AmpliPrep/Cobas TaqMan 2.0. A higher risk for LLV but not for VF was found in patients with a higher VL before ART and shorter ART duration. A higher risk for VF but not for LLV was found in patients of younger age, originating from a high prevalence country, with a lower CD4 count and in male injecting drug users. Conclusions This study of well-defined patients on stable ART over a period of more than six months gives insights into the different factors associated with LLV and VF. In patients with VF, factors associated with adherence play a prominent role, whereas in patients with LLV, the biology of viral replication comes additionally into effect. Despite its observational design, it has implications for patient management and forms the basis for future outcome studies. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Higher blood levels of the essential amino acid phenylalanine (phe) have been documented in patients with HIV-1 infection. They may relate to a diminished conversion of phe to tyrosine (tyr) by the enzyme phenylalanine-hydroxylase (PAH). PAH is rate-limiting in the biosynthesis of dopamine, and impaired PAH activity is reflected by an increased phe to tyr ratio (phe/tyr). Methods: Plasma phe/tyr was measured in 107 patients with HIV-1 infection before and after 12months of effective antiretroviral therapy (ART). Results were compared with CD4+ cell counts, HIV-1 RNA levels and concentrations of immune activation marker neopterin. Results: Before ART, phe/tyr was mean±S.D.: 0.99±0.57μmol/μmol. Phe/tyr correlated significantly with plasma and urine neopterin concentrations (rs =0.434, and rs =0.392; both p <0.001) and less strongly with HIV-RNA levels (rs =0.173) and CD4+ counts (rs =−0.182, both p <0.05). After ART, phe/tyr dropped to 0.72±0.16 (=−27%; U =5.21, p =0.01) which was due to an average decline of −14% of phe concentrations from 73.1±34.0μmol/L at baseline to 62.9±17.8μmol/L after ART (U =2.51, p =0.01) and a concomitant increase of tyr concentrations (+13%, U =2.46, p =0.01). In parallel, significant reductions of plasma and urine neopterin concentrations were observed during ART. Conclusions: Increased phe/tyr is frequent in patients with HIV-1 infection and is related to immune activation. ART was found to decrease phe/tyr and this change could indicate and influence on PAH activity. Future studies might be able to show whether the decline of phe/tyr under ART may concur with the often improved neuropsychiatric status in treated patients. [Copyright &y& Elsevier]