Dolutegravir-based regimen maintains virological success in a patient with archived mutations to integrase inhibitors

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Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic

Introduction: Patients affected by Inborn Errors of Immunity (IEI) represent a potential group-at-risk in the current COVID-19 pandemic. Studies on large and small cohorts of IEI reported a huge variability clinical manifestations associated to SARS-Cov-2, ranging from asymptomatic, mild, moderate/severe to death. A great impulse to improve remote assistance programs and to switch to home-based treatment to reduce mobility and face to face contacts has been implemented. Areas covered: The authors completed a comprehensive review of the literature by searching the PubMed database for studies on large and small cohorts and case reports of IEI patients with COVID-19, with the aim to provide useful information for their clinical management during the COVID-19 pandemic. Expert opinion: Surprisingly, a low number of IEI patients affected by SARS-Cov-2 were reported with a risk to die for COVID-19 overlapping that of the general population. The low number might be explained by the choice of most physicians to inform early in the pandemic about safety measures, to switch most of the IEI patients to home therapy and to remote assistance. The guidelines issued by the scientific societies and periodically updated, represent the best tool for the clinical management of IEI patients

Usefulness of calcaneal quantitative ultrasound stiffness for the evaluation of bone health in HIV-1-infected subjects: Comparison with dual X-ray absorptiometry

Objectives: With the development of effective treatments and the resulting increase in life expectancy, bone mineral density (BMD) alteration has emerged as an important comorbidity in human immunodeficiency virus type-1 (HIV-1)-infected individuals. The potential contributors to the pathogenesis of osteopenia/osteoporosis include a higher prevalence of risk factors, combined antiretroviral therapy (cART)-exposure, HIV-1 itself and chronic immune activation/inflammation. Dual-energy X-ray absorptiometry (DXA) is the “gold standard” technique for assessing bone status in HIV-1 population. Methods: We conducted a cross-sectional study to investigate bone mineral status in a group of 158 HIV-1-infected subjects. The primary endpoint was the feasibility of calcaneal quantitative ultrasound (QUS) as a screening tool for BMD. All subjects were receiving stable cART and were virologically suppressed (HIV-RNA <37 copies/mL) from at least 12 months. Calcaneal QUS parameters were analyzed to obtain information on bone mass and microarchitecture. The results were compared with those obtained by DXA. Results: No correlations were found between DXA/QUS parameters and demographic or HIV-1-specific characteristics, also including cART strategies. In the univariate analyses BMD, QUS indexes, and Fracture Risk Assessment Tool scores conversely showed significant associations with one or more demographic or HIV-1-related variables. Moreover, a significant relationship between calcaneal quantitative ultrasound index/stiffness and femoral/lumbar BMD values from DXA was described. The multivariate analysis showed an independent association between calcaneal quantitative ultrasound index/stiffness and body mass index, higher CD4+T-cell numbers and low 25-OH D2/D3 vitamin D levels <10 ng/mL (P-values: 0.004, 0.016, and 0.015, respectively). Conclusion: As an alternative and/or integrative examination to DXA, calcaneal QUS could be proposed as a useful screening in HIV-1-infected patients for assessing bone health impairment. In fact, the results obtained confirm that calcaneal QUS may be useful for monitoring bone status, being a noninvasive and inexpensive technique, especially in those subjects with the classical traditional risk factors for bone damage that were observed earlier in HIV-1 population

A case of acanthosis nigricans in a HIV-infected patient

Background: To date, very little information is available concerning the relationship between acanthosis nigricans (AN) and infection with human immunodeficiency virus type 1 (HIV-1). Case presentation: Herein, we report the case of a middle-aged man admitted for fever and progressively worsening dyspnea in the context of an opportunistic pneumonia and firstly diagnosed with acquired immunodeficiency syndrome (AIDS). At the time of diagnosis, physical examination revealed the presence of a palpable, hyperpigmented skin lesion on the left areola with surface desquamation and velvety texture consistent with AN. Of note, the most common primary etiologies related to AN were excluded and the complete regression of the skin lesion was observed once antiretroviral therapy was started. Conclusion: This is the second report of AN found in patients with AIDS and apparently responsive to prolonged antiretroviral treatment. Possible explanations of this association are still not completely understood, probably related to virus-induced changes in lipid metabolism. Our experience suggests that HIV testing should always be considered in the setting of apparently idiopathic AN

Backbone switch to abacavir/lamivudine fixed-dose combination: implications for antiretroviral therapy optimization

Current guidelines recommend treatment optimization in virologically suppressed patients through switching/ simplification strategies to minimize long-term toxicities and improve adherence. The assessment of inflammation/ coagulation profiles may support therapeutic decisions. We undertook a prospective, non-randomized study to evaluate the efficacy and safety of switching to ABC/3TC from ZDV/3TC or TDF/FTC backbones, in 40 HIV-1 infected patients with HIV-RNA levels 24 months). Main endpoints were viral load levels, CD4+ T cells and toxicities after 48 weeks. Serum inflammation/coagulation markers (ESR, CRP, D-dimer and fibrinogen) and pro-inflammatory cytokines (IL-6, TNF-α, adiponectin, resistin) were evaluated. Baseline characteristics were similar in the two arms, with significantly lower values of e-GFR in patients on TDF/FTC. Markers of inflammation/ coagulation and cytokine profile were also similar, except for higher values of resistin in patients on TDF/ FTC. During follow up, CD4+ T cells increased and viral load remained undetectable in both groups. Patient from ZDV/3TC had significantly greater changes in total cholesterol and serum creatinine. Markers of inflammation/ coagulation remained unchanged. Adiponectin significantly increased in patients from ZDV/3TC. Switching to ABC/3TC was effective and safe. Inflammatory markers remained low in both groups. Some changes in metabolic, kidney and cytokine profiles were apparently specific for baseline cART treatment

Human Infection with Cryptosporidium felis: Case Report and Literature Review

An infection with Cryptosporidium felis in an HIV-positive man from Italy was successfully treated with paromomycin, despite the patient’s having a CD4+ cell count of 31/mL. Fourteen cases of human infection with C. felis have been described, all in the past 3 years, emphasizing the public health importance of Cryptosporidium parasites other than C. parvum

Management of HIV-1 associated hepatitis in patients with acquired immunodeficiency syndrome: role of a successful control of viral replication

In HIV-1 infected patients, increase of liver enzymes may be mainly due to viral coinfections, alcohol intake, hepatotoxic drugs or autoimmune diseases. Three cases of aminotransferase elevation occurred during a phase of uncontrolled viral replication combined with a severe immunodeficiency and resolved by an effective HAART are described, focusing on the etio-pathogenetic role possibly played by HIV-1 infection

MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients

Abstract BACKGROUND: Several in vitro studies suggested the microRNA-29 (miRNA-29) family is involved in regulating HIV-1 and modulating the expression of interleukin (IL)-32, an anti-HIV-1 cytokine. METHODS: To investigate the contribution of the miRNA-29 family to HIV-1 infection in vivo, we compared miRNA-29 expression in PBMC collected from 58 HIV-1-infected patients, naïve for antiretroviral therapy, and 21 gender- and age-matched HIV-1 seronegative healthy donors, using RT-Taqman assays. The relation between miRNA-29 levels and HIV-1 viro-immunological markers and the activation rate of antiviral immune response were also evaluated. In addition, we profiled miRNA-29 expression in CD4+ T lymphocytes and CD14+ monocytes collected from 5 antiretroviral treated HIV-1 infected patients. RESULTS: miRNA-29b levels were higher in HIV-1-infected patients than in the control group (p < 0.001). There were no correlations with either HIV-1 RNA levels or CD4+ T count, whereas a significant correlation was found between miRNA-29-a/c levels and integrated HIV-1 DNA (miRNA-29a: p = 0.009, r = -0.448; miRNA-29c: p = 0.029; r = -0.381). When the HIV-1-infected patients were grouped on the basis of their plasma HIV-1 RNA and CD4+ T cell count, we also found that patients expressing the lowest levels of miRNA-29c showed high viraemia, low CD4+ T cell count and high levels of integrated HIV-1 DNA. Moreover, miRNA-29b levels were correlated with those of IL-32nonα (p = 0.028; r = -0.298). Patients expressing higher levels of miRNA-29b showed lower levels of MxA, an interferon-stimulated gene, also induced by IL-32 (p = 0.006 r = -0.397). Lastly, we found that CD4+ T lymphocytes and CD14+ monocytes shared similar miRNA-29a/b/c expression patterns but the amount of miRNA-29a/b/c, IL-32 isoforms and MxA were highly variable in these two cellular subsets. CONCLUSIONS: The miRNA-29 family could influence the clinical progression of HIV-1 infection, the HIV-1 proviral load and the innate immune response against HIV-1

HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity.

OBJECTIVES: HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress. METHODS: We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α). RESULTS: sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p &lt; 0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p &lt; 0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p &lt; 0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels. CONCLUSIONS: HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress

Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents

Association between HCV infection and diabetes has been widely postulated. Little is known about the impact of direct acting antiviral agents (DAAs) on glycemic control. Aim of our study was to evaluate the glycemic control modifications in a case series of HCV+ diabetic population receiving DAAs. We retrospectively evaluated 149 HCV+ patients in two different institutions affiliated to the Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with T2DM (19% of total population) who were receiving different IFN-free regimens. During-treatment fasting glucose values were available for 21 patients and analysis showed a statistically significant reduction (p=0,007), the reduction mean value was -52,86 mg/dl. An A1C value during treatment (week 4 or week 8 or week 12) was available for 10 patients and the analysis showed a statistically significant reduction (p=0,021) with a reduction mean value of -1,95%. 6 patients (23%) needed to reduce hypoglycemic drugs, 8 of 10 patients showed reduction of A1C, 14 of 21 patients (67%) showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, BMI and HIV status. In order to avoid hypoglycemic events, diabetic patients undergoing DAAs should be closely monitorized for reduction of hypoglycemic drugs. Furthermore, diabetes could be considered, in our opinion, as an element to prioritize treatment in those patients with no apparent liver disease