Purpose
Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors.
...Methods
We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004–2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors.
Results
Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use.
Conclusion
Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.
People with HIV have a higher risk of fracture than the general population. Because of the low performance of the existing prediction tools, there is controversy surrounding fracture risk estimation ...in this population. The aim of the study was to develop a model for predicting the long-term risk of fragility fractures in people with HIV. We included 11,899 individuals aged ≥ 30 years from the Spanish HIV/AIDS research network cohort. We identified incident fragility fractures from medical records, defined as those non-traumatic or occurring after a casual fall, at major osteoporotic sites (hip, clinical spine, forearm, proximal humerus). Our model accounted for the competing risk of death and included 12 candidate predictors to estimate the time to first fragility fracture. We assessed the discrimination and calibration of the model and compared it with the FRAX tool. The incidence rate of fragility fractures was 4.34 (95% CI 3.61-5.22) per 1,000 person-years. The final prediction model included age, chronic kidney disease, and chronic obstructive pulmonary disease as significant predictors. The model accurately predicted the five-year and ten-year risk of fragility fractures, with an area under the receiving operator characteristic curve of 0.768 (95% CI 0.722-0.814), and agreement between the observed and expected probabilities. Furthermore, it demonstrated better discrimination and calibration than the FRAX tool, improving the classification of over 35% of individuals with fragility fractures compared to FRAX. Our prediction model demonstrated accuracy in predicting the long-term risk of fragility fractures. It can assist in making personalized intervention decisions for individuals with HIV and may potentially replace the current tools recommended for fracture risk assessment in this population. This article is protected by copyright. All rights reserved.
Objectives
To describe prevalence and factors associated with unplanned pregnancies, and social and partner support during pregnancy among women from the Cohort of the Spanish HIV/AIDS Research ...Network (CoRIS).
Methods
We included all women recruited in CoRIS from 2004 to 2019, aged 18–50 years at recruitment who were pregnant during 2020. We designed a questionnaire, organized into the following domains: sociodemographic characteristics, tobacco and alcohol consumption, pregnancy and reproductive health, and social and partner support. The information was gathered via telephone interviews conducted from June to December 2021. We calculated prevalence of unplanned pregnancies as well as odds ratios (ORs) of association and 95% confidence intervals (CIs) according to sociodemographic, clinical and reproductive characteristics.
Results
Among 53 women who were pregnant during 2020, 38 (71.7%) answered the questionnaire. Median age at pregnancy was 36 years interquartile range (IQR) 31–39, 27 (71.1%) women were born outside of Spain, mainly in sub‐Saharan Africa (39.5%) and 17 (44.7%) were employed. Thirty‐four (89.5%) women had been through previous pregnancies and 32 (84.2%) had experienced previous abortions/miscarriages. Seventeen (44.7%) women had shared with their clinician their desire to get pregnant.
Thirty‐four (89.5%) pregnancies were natural and four used assisted reproductive techniques (in vitro fertilizations; one additionally used oocyte donation). Of 34 women with natural pregnancies, pregnancy was unplanned in 21 (61.8%) and 25 (73.5%) had information on how to become pregnant avoiding HIV transmission to the baby and partner. Women who did not seek advice from their physician about becoming pregnant had a significantly increased risk of unplanned pregnancy (OR = 71.25, 95% CI: 8.96–566.67).
Overall, 14 (36.8%) women reported having low social support during pregnancy and 27 (71.0%) had good/very good support by their partner.
Conclusions
Most pregnancies were natural and unplanned and very few women had talked with their clinician about their desire to become pregnant. A high proportion of women reported low social support during pregnancy.
Latent parasitic infections can reactivate because of immunosuppression. We conducted a prospective observational study of all human immunodeficiency virus (HIV)-infected immigrants who visited the ...Infectious Diseases Department of the Hospital Universitari Vall d'Hebron, Barcelona, Spain, during June 2010-May 2011. Screening of the most prevalent tropical diseases (intestinal parasitosis, Chagas disease, leishmaniasis, malaria, schistosomiasis, and strongyloidiasis) was performed according to geographic origin. A total of 190 patients were included: 141 (74.2%) from Latin America, 41 (21.6%) from sub-Saharan Africa, and 8 (4.2%) from northern Africa. Overall, 36.8% (70 of 190) of the patients had at least one positive result for any parasitic disease: 5 patients with positive Trypanosoma cruzi serology, 11 patients with positive Schistosoma mansoni serology, 35 patients with positive Strongyloides stercoralis serology, 7 patients with positive Leishmania infantum serology, intestinal parasitosis were detected in 37 patients, malaria was diagnosed in one symptomatic patient. We propose a screening and management strategy of latent parasitic infections in immigrant patients infected with HIV.
Rezolsta® (darunavir/cobicistat) is the first boosted protease inhibitor in a fixed-dose combination to be approved for the treatment of HIV infection. It contains darunavir, a protease inhibitor ...with a well-known safety and efficacy profile, and the new pharmacokinetic enhancer cobicistat. The convenience of this combination makes boosted darunavir easier to take, thus improving adherence. Exposure to darunavir is equivalent when it is administered with cobicistat or with ritonavir. Darunavir/cobicistat-based antiretroviral therapy has shown considerable efficacy and good tolerability in several clinical trials. Data from the single-arm, open-label, phase III GS-US-216-130 trial showed virological efficacy rates comparable to those from ARTEMIS and ODIN. Darunavir/cobicistat was well tolerated; most adverse events were mild and consisted of gastrointestinal disturbances. Cobicistat inhibits transporters of creatinine in kidney tubules, thus causing a minimal and reversible reduction in estimated glomerular filtration rate. Like ritonavir, cobicistat is a strong CYP3A4 inhibitor and, as such, shares most of its drug interactions. However, inhibition by cobicistat seems to be more specific than with ritonavir, and cobicistat has no inducer effect; therefore, differences in its drug interaction profile may be observed.
Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of ...the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background. It is unknown if tenofovir disoproxil fumarate (TDF), which is often coformulated with the lipid-neutral emtricitabine (FTC), has a lipid-lowering effect. Methods. We performed a ...randomized, crossover, double-blind, placebo-controlled clinical trial on human immunodeficiency virus type 1 (HIV-1)–infected subjects with HIV-1 RNA < 50 copies/mL during ≥6 months on stable darunavir/ritonavir (800/100 mg once daily) or lopinavir/ritonavir (400/100 mg twice daily) monotherapy, fasting total cholesterol (TC) ≥200 mg/dL or low-density lipoprotein cholesterol (LDL-c) ≥130 mg/dL, and no lipid-lowering drugs. In arm 1, TDF/FTC was added for 12 weeks, followed by 12 weeks of placebo (washout) and 12 additional weeks of placebo (placebo period). Subjects in arm 2 added placebo for 12 weeks (placebo period) followed by TDF/FTC for 12 weeks and placebo for 12 additional weeks (washout). The primary endpoint was change in median fasting TC levels. Results. Of 46 subjects enrolled, 56% received darunavir/ritonavir and 44% lopinavir/ritonavir. Exposure to TDF/FTC reduced TC from 234 to 205 mg/dL (P < .001), LDL-c from 155 to 128 mg/dL (P < .001), and high-density lipoprotein cholesterol (HDL-c) from 50.3 to 44.5 mg/dL (P < .001). It also decreased the proportion of subjects with fasting TC ≥200 mg/dL from 86.7% to 56.8% (P = .001), and LDL-c ≥130 mg/dL from 87.8% to 43.9% (P < .001). After 12 weeks, TDF/FTC exposure was associated with lower TC and LDL-c levels than placebo (P = .001 and P = .002, respectively). The TC/HDL-c ratio and triglyceride levels did not change with TDF/FTC exposure. Conclusions. Coformulated TDF/FTC has an intrinsic lipid-lowering effect, likely attributable to TDF. Clinical Trials Registration. NCT01458977.
•The CD4+/CD8+ ratio pre-treatment is the strongest predictor of immune recovery.•The immune benefits of early antiretroviral therapy might derive from higher pre- antiretroviral therapy CD4+/CD8+ ...ratios.•Treatment with integrase inhibitors might be related to earlier immune recovery.
We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response.
Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load VL <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis.
ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003).
The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.
Our objective was to assess the therapeutic noninferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus 2 nucleos(t)ides for ...maintenance of human immunodeficiency virus type 1 (HIV-1) suppression.
This was a multicenter, open-label, noninferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for 6 months or longer on triple therapy with darunavir/ritonavir and 2 nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine) and with no resistance were randomized to continue therapy (n = 128) or switch to darunavir/ritonavir and lamivudine (n = 129). The primary endpoint was the proportion of participants with HIV-RNA <50 copies/mL after 48 weeks of follow-up according to the snapshot algorithm.
A total of 249 participants received study drugs (intention-to-treat exposed). The proportion of participants with HIV-RNA <50 copies/mL in the dual- and triple-therapy arms was 88.9% (112/126) and 92.7% (114/123; difference, -3.8%; 95% confidence interval, -11.0 to 3.4), respectively. Four participants in the dual-therapy arm and 2 in the triple-therapy arm developed protocol-defined virological failure. Switching to dual therapy was associated with a significant increase in total, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, but not in the total-to-HDL cholesterol ratio. Serious adverse events and study drug discontinuations due to adverse events occurred in 4.8% vs 4.9%P = .97) and in 0.8% (1/126) vs 1.6% P = .55) in dual therapy vs triple therapy, respectively.
Dual therapy with darunavir/ritonavir and lamivudine demonstrated noninferior therapeutic efficacy and similar tolerability compared to triple therapy.
NCT02159599.
Introduction
The objective was to characterize real-world outcomes of drug–drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and ...treatment outcomes in clinical practice.
Methods
www.clinicalcasesDDIs.com
is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023.
Results
A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case).
Conclusions
Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through
www.clinicalcasesDDIs.com
serves as a valuable resource for assessing the clinical relevance of DDIs.
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