We assessed the vaccination effectiveness (VE) of multicomponent meningococcal serogroup B (4CMenB) vaccine against gonorrhea among people living with HIV (PLWH) with a previous diagnosis of sexually ...transmitted infection.
Unmatched case-control study on men who have sex with men living with HIV, in care at San Raffaele Scientific Institute, Milan, Italy, with gonorrhea, syphilis, chlamydia, or anal human papillomavirus between July 2016 (beginning of 4CMenB vaccination) and February 2021 (date of freezing). For the analysis, cases were people with ≥1 gonorrhea infection since July 2016, and controls were people with ≥1 syphilis, chlamydia, or anal human papillomavirus infection since July 2016. Logistic regression was used to provide the estimate of 4CMenB VE against gonorrhea.
Included people living with HIV were 1051 (103 cases, 948 controls); 349 of 1051 (33%) received 2 doses of 4CMenB vaccination. The median follow-up was 3.8 years (2.1-4.3 years). The unadjusted estimate for VE against gonorrhea was 42% (95% confidence interval, 6%-64%; P = 0.027). Logistic regression showed that VE against gonorrhea remained significant (44%; 95% confidence interval, 9%-65%; P = 0.020) after adjusting for some factors that might have a potential influence on VE or those with significant unbalanced distributions between cases and controls at univariable analysis.
4CMenB vaccination is associated with a lower risk of gonorrhea in the setting of men who have sex with men living with HIV with a previous sexually transmitted infection.
Aim of this review is to focus the attention on people living with HIV infection at risk of developing a cardiovascular event. What is or what would be the most suitable antiretroviral therapy? Which ...statin or fibrate to reduce the risk? How to influence behavior and lifestyles?
Prevention of cardiovascular disease (CVD) risk remains the first and essential step in a medical intervention on these patients. The lifestyle modification, including smoking cessation, increased physical activity, weight reduction, and the education on healthy dietary practices are the main instruments. Statins are the cornerstone for the treatment of hypercholesterolemia. They have been shown to slow the progression or promote regression of coronary plaque, and could also exert an anti-inflammatory and immunomodulatory effect. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. The debate between American and European guidelines is still open and, also considering the independent risk factor represented by HIV, specific guidelines are warranted. Ezetimibe reduces the intestinal absorption of cholesterol. It is effective alone or in combination with rosuvastatin. It does not modify plasmatic concentrations of antiretrovirals. A number of experimental new classes of drugs for the treatment of hypercholesterolemia are being studied. Fibrates represent the first choice for treatment of hypertriglyceridemia, however, the renal toxicity of fibrates and statins should be considered. Omega 3 fatty acids have a good safety profile, but their efficacy is limited. Another concern is the high dose needed. Other drugs are acipimox and tesamorelin. Current antiretroviral therapies are less toxic and more effective than regimens used in the early years. Lipodistrophy and dyslipidemia are the main causes of long-term toxicities. Not all antiretrovirals have similar toxicities. Protease Inhibitors may cause dyslipidemia and lipodystrophy, while integrase inhibitors have a minimal impact on lipids profile, and no evidence of lipodystrophy. There is still much to be written with the introduction of new drugs in clinical practice.
Cardiovascular risk among HIV infected patients, interventions on behavior and lifestyles, use of drugs to reduce the risk, and switch in antiretroviral therapy, remain nowadays major issues in the management of HIV-infected patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
Aims of this study are assessing prevalence of anal human papillomavirus (HPV) genotypes in male who have sex with men (MSM) living with HIV over a period of 5 years and determining risk ...factors for anal infection from high-risk (HR) HPV genotypes or included in vaccine Gardasil 9.
Setting:
Time–trend, monocentric study on MSM living with HIV who underwent HPV test at anal site from 2015 to 2019.
Methods:
Anal swabs were processed by multiplex real-time polymerase chain reaction to detect HPV genotypes. The Cochran–Armitage test was used to assess linear trend in HPV prevalence over time and logistic regression models to estimate risk factors.
Results:
Of the 1352 MSM living with HIV, 168 (12%) were not infected by any HPV genotypes and only 6 were infected with a maximum of 6 genotypes; prevalence of HR-HPV genotypes or those included in the 9-valent vaccine remained stable over time. At multivariable analysis, the risk of carrying at least 1 genotype classified as HR or included in Gardasil 9 was associated with younger age adjusted odds ratio (aOR) for younger than 30 years vs older than 45 years (95% confidence interval) 2.714 (1.484 to 4.961),
P
= 0.001, and 1.868 (1.141 to 3.060),
P
< 0.013, respectively and a history of gonorrhea aOR 2.118 (1.100 to 4.078),
P
= 0.025, and 1.785 (1.056 to 3.018),
P
= 0.031, respectively.
Conclusion:
Our findings suggest that prevalence remained stable over time and that all MSM with HIV would benefit from Gardasil 9 immunization, particularly the youngest and those with a prior gonococcal infection.
Darunavir for the treatment of HIV infection Spagnuolo, Vincenzo; Castagna, Antonella; Lazzarin, Adriano
Expert opinion on pharmacotherapy,
07/2018, Volume:
19, Issue:
10
Journal Article
Peer reviewed
Introduction: Darunavir (DRV) was the last approved protease inhibitor (PI) and has been extensively used for the treatment of HIV in both naïve and experienced subjects due to its high genetic ...barrier and efficacy. The introduction in clinical practice of integrase strand transfer inhibitors limited its role in the management of naïve subjects and in antiretroviral treatment simplification strategies. However, recent data from trials that have investigated the new DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) combination showed an excellent efficacy and tolerability of this coformulation both in naïve patients and in those with viral suppression, making D/C/F/TAF a new option for the treatment of HIV infection.
Areas covered: The authors present and discuss the efficacy and safety data of DRV when used in antiretroviral-naïve, multiexperienced subjects and in the setting of treatment deintensification in subjects with viral suppression. Moreover, the authors evaluate the recent data from two different Phase III trials on D/C/F/TAF both in treatment-naïve and virologically suppressed subjects.
Expert opinion: Although novel antiretroviral drugs may become available over time, DRV continues to represent a valuable option for multiexperienced subjects and has a role in simplification regimens. In addition, the convenience of D/C/F/TAF coformulation may be useful for the future management of HIV-infected subjects.
HLA-B27 and -B57 were found in people with low levels of HIV-1 DNA, suggesting that HLA class I molecules may influence the size of HIV-1 reservoir. Aim of the study was to explore the association ...between HLA class I molecules and HIV-1 DNA in people with chronic HIV-1 infection.
Post-hoc analysis of the APACHE trial, on adults with chronic HIV-1 infection, prolonged suppressive antiretroviral therapy and good immunological profile. HIV-1 DNA was quantified in peripheral blood mononuclear cells (PBMCs); HLA-A, -B and -C were tested on genomic DNA. Crude odds ratios (OR) with their respective 95% Wald confidence intervals (95% CIs) were estimated by univariable logistic regression for HLAs with a p-value <0.10.
We found 78 and 18 patients with HIV-1 DNA ≥100 copies/106PBMCs and with HIV-1 DNA <100 copies/106PBMCs, respectively. HLA-A24 was present in 21 (29.6%) participants among subjects with HIV-1 DNA ≥100 copies/106PBMCs and 1 (5.9%) among those with HIV-1 DNA <100 copies/106PBMCs (OR = 5.67, 95%CI = 0.79-46.03; p = 0.105); HLA-B39 was present in 1 (1.4%) with HIV-1 DNA ≥100 copies/106PBMCs and in 3 (17.6%) with HIV-1 DNA <100 copies/106PBMCs (OR = 13.71, 95%CI = 1.33-141.77; p = 0.028) and HLA-B55 in 3 (4.2%) and 3 (17.6%), respectively (OR = 4.43, 95%CI = 0.81-24.29; p = 0.087). All the three patients with HLA-B39 and HIV-1 DNA <100 copies/106PBMCs did not have HLA-A24.
In patients with HIV-1 infection who maintained a good virological and immunological profile, HLA-B39 and -B55 may be associated with lower levels of HIV-1 DNA.
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Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. ...Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+ G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.
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•Heavily treatment-experienced people living with HIV (PLWH) often have few antiretroviral drugs available.•As of the end of 2021, heavily treatment-experienced (HTE) patients account for 0.01% of ...PLWH in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort.•Lower clusters of differentiation 4 counts and hepatitis C virus positivity increase the risk of becoming HTE.•Some HTE individuals currently exhibit ongoing immune-virological failure.•This special group of HTE PLWH is a potential candidate for new antiviral drugs.
Heavily treatment-experienced (HTE) people living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up in the Italian Cohort Naïve Antiretrovirals (ICONA) cohort as of December 31, 2021.
HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021. Descriptive statistics were performed by HTE status. Regression analyses explored factors associated with becoming HTE based on pre-ART patients' characteristics. Cluster dendrogram analysis provided insights into subgroups with inadequate responses based on clusters of differentiation (CD4) counts and viral load (VL) trajectories.
Among the 8758 PLWH actively followed in our cohort, 163 individuals (1.9%), mainly female, younger, Italian, and infected through heterosexual contact, met the HTE criteria. A lower CD4 count at ART initiation (odds ratio OR 1.60 per 100 cells/mmc lower CD4, 95% confidence interval CI 1.06-2.41, P = 0.03) and hepatitis C virus antibody positivity (OR 1.90, 95% CI 1.16-3.11, P = 0.01) were associated with higher HTE risk. Thirty PLWH exhibited ongoing immune-virological failure (18% of the HTE subgroup and 0.003% of the total population). Thirty PLWH exhibited ongoing immune-virological failure (i.e., with a current CD4 count <200 cells/mmc or VL>200 copies/mL). A cluster analysis identified 13 (43%) with a current CD4 count <200 cells/mmc. Also, notably, 19/30 (63%) had major acquired resistance-associated mutations to at least one antiretroviral drug class.
HTE is rare in our cohort and tends to co-exist with major resistance mutations. A focused investigation into treatment history and immuno-virological response is warranted, particularly given the availability of new antiretroviral drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PurposeThe PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance ...(4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population.ParticipantsThe PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry.Findings to dateThe open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples.Future plansThe registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole.Trial registration numberNCT04098315.
Antibodies against hepatitis B core antigen (anti-HBc) are found in 14-44% of patients with HIV infection, but it is still unclear whether hepatitis B virus (HBV) vaccination should be recommended ...for HIV-positive subjects with isolated anti-HBc (IAHBc). We examined the rate of anamnestic and primary responses (ARs and PRs) and associated factors in a group of HIV-infected patients with an IAHBc profile.
This prospective study recruited 25 HIV-positive patients with anti-HBc alone who were vaccinated against HBV infection. Those without an AR (anti-hepatitis B envelope antigen anti-HBs levels of <10 U/L) or who were hypo-responsiveness (anti-HBs levels of >10 but <100 U/L) four weeks after the first dose of vaccine underwent a full course of vaccinations. Their clinical and virological data, including the presence of occult hepatitis B infection (OBI), were evaluated in accordance with the vaccination schedule.
Six of the 25 patients (24%) showed an AR, four of whom had anti-HBs levels of <100 U/L. Ten of 19 (52.6%) remaining patients became seroprotected after the third dose. OBI was detected in four of the six patients with an AR, two of the 10 patients with a PR, and none of the nine patients who did not respond. Multivariate analysis showed that an AR was associated with the presence of OBI (P = 0.0162), and a PR was associated with HCV antibody status. (P = 0.0191).
Our data suggest that testing for anti-HBc alone may not be a reliable means of assessing protection from HBV infection in HIV-positive patients. OBI-positive patients may benefit from a single vaccine dose. Anti-HCV serostatus may affect PRs.
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Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations.
We report the case of ...a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi's sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks.
M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi's sarcoma) cannot be excluded.
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