Background. Polysaccharide pneumococcal vaccine (PPV) is recommended among human immunodeficiency virus (HIV)–infected patients, although its effect in reducing the incidence of pneumonia or invasive ...pneumococcal disease is not well established. Our objective was to determine the effectiveness of 23-valent PPV in HIV-infected adults and the risk factors for pneumococcal pneumonia or invasive pneumococcal disease. Methods. We performed a retrospective case-control study in 4 Spanish hospitals for the period from January 1995 through December 2005 using the HIV database from each hospital to identify case patients with Streptococcus pneumoniae disease and control subjects without a history of pneumococcal infection. Results. A total of 184 case patients and 552 control subjects were identified. The factors associated with pneumococcal disease in bivariate analysis were active injection drug use (odds ratio OR, 3.33; 95% confidence interval CI, 2–5.55), alcoholism (OR, 3.03; 95% CI, 1.86–4.91), chronic obstructive pulmonary disease (OR, 2.58; 95% CI, 1.3–5.1), cirrhosis (OR, 6.05; 95% CI, 3.2–11.4), antiretroviral therapy (OR, 0.23; 95% CI, 0.16–0.32), trimethoprim-sulfamethoxazole prophylaxis (OR, 0.66; 95% CI, 0.45–0.97), viral load <5000 copies/mL (OR, 0.38; 95% CI, 0.26–0.54), and previous PPV (OR, 0.39; 95% CI, 0.24–0.65). Risk factors for pneumococcal disease in multivariate analysis were cirrhosis (OR, 5.64; 95% CI, 2.53–12.53), chronic obstructive pulmonary disease (OR, 2.90; 95% CI, 1.21–6.94), and alcoholism (OR, 2.15; 95% CI, 1.11–4.19), whereas protective factors were receipt of antiretroviral therapy (OR, 0.23; 95% CI, 0.14–0.36) and receipt of pneumococcal vaccine (OR, 0.44; 95% CI, 0.22–0.88), even in patients with CD4 lymphocyte counts <200 cells/µL. Conclusions. Antiretroviral therapy and PPV have a significant, independent protective effect against pneumococcal disease, regardless of CD4 lymphocyte count; thus, all patients with HIV infection should be vaccinated with PPV to prevent pneumococcal disease.
Abstract
Background
The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in ...the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH.
Methods
We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS).
Discussion
The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented.
Trial registration
ClinicalTrials.gov
NCT04735445. Registered on 25 June 2019
Background
HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases ...coagulation potentially through alterations in extrinsic pathway factors.
Methods and Results
Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti‐Retroviral Therapy (SMART) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy (ART) treatment versus the untreated state (HIV replication) via 3 separate analyses: (1) a cross‐sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short‐term increases in some procoagulants (eg, 15% to 23% higher FVIII; P<0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin AT and 6% to 10% lower protein C; P<0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P<0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons.
Conclusions
HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV‐related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation.
Clinical Trial Registration
URL: ClinicalTrials.gov. Unique identifier: NCT00027352.
Resumen Este estudio se ha centrado en las actuaciones a nivel político y administrativo que se han realizado en España en relación con la implementación de la profilaxis preexposición (PrEP) al VIH. ...Se ha analizado todo tipo de iniciativas formales por parte de los actores políticos y administrativos implicados. Las fuentes utilizadas son las fuentes oficiales públicas. Hasta febrero de 2018, la PrEP no ha sido implementada. La decisión depende de los niveles estatal y autonómico. El Ministerio de Sanidad y algunas Comunidades Autónomas trabajan en diversas intervenciones sin establecer un calendario de implementación. Los partidos políticos por su parte han promovido escasas iniciativas relacionadas con la implementación de la PrEP. En el terreno jurídico, se han producido vaivenes legales relacionados con la extensión de la patente. El papel de los órganos intergubernamentales e interdepartamentales es vital para la implementación de la PrEP.
OBJECTIVES:To evaluate the efficacy and safety of switching from boosted lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1-infected patients versus continuing LPV/r.
...METHODS:Forty-eight weeks analysis of a randomized, open-label, noninferiority trial including patients with virological suppression (≤200 copies/mL for ≥6 months) on LPV/r-containing triple highly active antiretroviral therapy. Patients (n = 248) were randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse transcriptase inhibitor backbone. Those known to have >4 protease inhibitor (PI)-associated mutations and/or who had failed >2 PI-containing regimens were excluded.
RESULTS:Baseline characteristics were balanced. 30% harboured ≥1 PI-associated mutation (10% harboured ≥1 major mutation). Treatment failure at 48 weeks (primary end point) occurred in 20% (25 of 127) of the LPV/r arm and in 17% (21 of 121) of the ATV/r arm (difference −2.3%; 95% confidence interval−12.0 to 8.0; P = 0.0018). Virological failure occurred in 7% (9 of 127) of the LPV/r arm and in 5% (6 of 121) of the ATV/r arm (difference −2.1%; 95% confidence interval−8.7% to 4.2%, P < 0.0001 for noninferiorating). CD4 changes from baseline were similar in each arm (approximately 40 cells/mm). Adverse event rate leading to study drug discontinuation was 5% in both arms. Median fasting triglycerides and total cholesterol decreased significantly in the ATV/r arm (−53 and −19 mg/dL, respectively versus −4 and −4 mg/dL in the LPV/r arm; P < 0.001 in both comparisons). Alanine aminotransferase/aspartate aminotransferase hepatic abnormalities were similar in the 2 arms.
CONCLUSIONS:Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r-containing highly active antiretroviral therapy provided comparable (noninferior) efficacy and a safety profile with improved lipid parameters ISRCTN24813210.
A clinical trial comparing the rate of discontinuation and tolerability of two post-exposure prophylaxis (PEP) regimens was performed.
A total of 255 individuals attending the emergency rooms of six ...hospitals for exposure to HIV and criteria to receive PEP were randomized to receive zidovudine/lamivudine plus either lopinavir/ritonavir (n=131) or atazanavir (n=124; day 0). The primary end point was the rate of PEP discontinuation before day 28 of follow-up. Secondary end points were incidence of side effects, follow-up at days 90 and 180 and rate of seroconversions.
A total of 55 patients (29 in lopinavir/ritonavir and 26 in atazanavir arms) did not attend the first scheduled appointment (day 1) and were excluded from the analysis. The rate of discontinuation before day 28 owing to any cause was similar between groups (37/102 36% in lopinavir/ritonavir and 35/98 36% in atazanavir arms, P=0.82). Adverse events were the reason for discontinuation or switching of PEP in 33 individuals (16/102 16% in the lopinavir/ritonavir arm and 17/98 17% in the atazanavir arm, P=0.84). Adverse events were reported in 92/200 (46%) of individuals on PEP who attend at least the day 1 appointment (50/102 49% in the lopinavir/ritonavir arm and 42/98 43% in the atazanavir arm, P=0.38). There were no seroconversions.
The rate of discontinuation of PEP before day 28 was similar with zidovudine/lamivudine plus either lopinavir/ritonavir or atazanavir. The rate of discontinuation of PEP because of adverse events was low in both arms. Almost 50% of the patients of both arms suffered side effects. New strategies are needed to improve the tolerance.
Objectives
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV‐infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir ...(ATV) inhibits UDP‐glucuronosyl‐transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)‐ vs. efavirenz (EFV)‐based first‐line antiretroviral therapy (ART).
Methods
A multicentre, prospective cohort study of HIV‐infected patients who started first‐line ART with either ATV/r or EFV was conducted. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2), myeloperoxidase (MPO) and oxidized low‐density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders.
Results
After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp‐PLA2 estimated difference −16.3; 95% confidence interval (CI) −31.4, −1.25; P = 0.03 and a significantly smaller increase in OxLDL (estimated difference −21.8; 95% CI −38.0, −5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI −14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated.
Conclusions
When compared with EFV, ATV/r‐based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
Gender-specific data on the management of HIV infection are scarce. Further, an increase in the proportion of new HIV diagnoses in older persons has been observed. Using data from the CoRIS cohort, ...we compared immunovirological responses and survival in HIV-infected men and women who started their first combination antiretroviral therapy (cART) when aged < /≥50 years.
We used multivariable logistic, linear and Cox regression, adjusting for potential confounders and including an interaction between age and sex, to assess differences in immunovirological responses and mortality, respectively.
At 96 weeks, among subjects <50 years, women were less likely than men to achieve virological response (VR; adjusted OR aOR 0.77, 95% CI 0.60, 0.99) and among women, older individuals were more likely to achieve VR than the younger ones (aOR 1.96; 95% CI 1.15, 3.34). Initiating cART at ≥50 years was associated with lower increases in CD4
T-cell count both in men (-65.8; 95% CI -91.3, -40.3) and women (-37.7; 95% CI -79.7, 4.4) and women showed higher increases than men in both subjects aged <50 (21.8; 95% CI -1.9, 45.5) and ≥50 years at cART initiation (49.9; 95% CI 19.9, 79.9). A higher risk of death in men ≥50 was observed (adjusted hazard ratio aHR 2.69; 95% CI 1.73, 4.21), but not in women (aHR 1.49; 95% CI 0.70, 1.14). Women experienced lower mortality than men <50 (0.66; 95% CI 0.41, 1.07) and in those ≥50 (0.37; 95% CI 0.14, 0.93).
Sex and age at cART initiation have a noticeable association with both virological and immunological responses and mortality. Age ≥50 is associated with poorer immunological response and higher mortality but this effect is less pronounced in women than in men.
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