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Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8 < 0.45 in the HIV/HBV coinfected group. A significant increase in the CD8 T cell count was shown up to 24 months after the initiation of effective cART in the subgroup of patients with the worst immune status.

A significant proportion of HIV-infected patients experiencing a late diagnosis highlights the need to define immunological protocols able to help the clinicians in identifying patients at higher risk for immunological failure. The aim of the study was to evaluate the feasibility of easy cytometric tests in defining the effect of antiretroviral treatment (cART) on immunological homeostasis and in identifying predictive markers of early immune recovery. Chronic HIV infected patients (n = 202) were enrolled in a prospective multicentric study, and their immunological profile was studied before (w0) and after 24 weeks (w24) of antiretroviral treatment (cART) using a standardized flow cytometric panel. Based on CD4 T cell count before treatment, patients were divided in late (LP: CD4 <350/mmc), intermediate (IP: 350/mmc500/mmc) presenters. In all groups, cART introduction increased CD4 and CD4/CD8 T cell ratio, naïve T cell (CD4 and CD8) and CD127-expressing CD4 T cells. In parallel, cART significantly reduced effector memory T cells (CD4 and CD8) and T cell activation (CD38+CD8 and CD95+CD4 T cells). Moreover, the frequency of Naïve and Effector CD4 T cells before treatment correlated with several immune parameters key associated with the pathogenesis of HIV, thus mirroring the health of immune system. Interestingly, we identified the Naïve/Effector CD4 T cell ratio (N/EM) at w0 as a marker able to predict early immune recovery. Specifically, in LP, N/EM ratio was significantly higher in immunological responder patients (CD4>500/mmc at w24) when compared to immunological non responder (CD4 T cells <500/mmc at w24). Finally, a multivariate analysis indicates that after 24w patients with N/EM ratio higher than 1.86 at w0 recovered 96 CD4 T cells more than those with N/EM ratio lower than 0.46. Altogether, our data define an easy protocol able to define reliable immunological markers useful for the characterization of immune profile in viremic HIV patients and identify the naïve/effector CD4 T cell ratio as a new tool able to predict an early immune reconstitution potential., Competing Interests: The support of Becton Dickinson does not alter our adherence to PLOS ONE policies on sharing data and materials.

The morbidity and mortality rates of human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection are higher than that of either infection alone. Outcomes and the virological response to antiretrovirals (combination antiretroviral therapy, cART) were explored in HIV/HBV subjects in a cohort of Italian patients treated with cART. A single-center retrospective analysis of patients enrolled from January 2007 to June 2018 was conducted by grouping patients by HBV status and recording baseline viro-immunological features, the history of virological failure, the efficacy of cART in achieving HIV viral undetectability, viral blip detection and viral rebound on follow up. Among 231 enrolled patients, 10 (4.3%) were HBV surface (s) antigen (HBsAg)-positive, 85 (36.8%) were positive for antibodies to HBV c antigen (HBcAb) and with or without antibodies to HBV s antigen (HBsAb), and 136 were (58.9%) HBV-negative. At baseline, HBcAb/HBsAb +/- -positive patients had lower CD4+ cell counts and CD4+ nadirs (188 cell/mmc, IQR 78-334, p = 0.02 and 176 cell/mmc, IQR 52-284, p = 0,001, respectively). There were significantly higher numbers of AIDS and non-AIDS events in the HBcAb + /HBsAb +/- -positive subjects than in the HBV-negative patients (41.1% vs 19.1%, p = 0.002 and 56.5% vs 28.7%, respectively, p ≤ 0.0001); additionally, HIV viremia undetectability was achieved a significantly longer time after cART was begun in the former than in the latter population (6 vs 4 months, p = 0.0001). Cox multivariable analysis confirmed that after starting cART, an HBcAb + /HBsAb +/- -positive status is a risk factor for a lower odds of achieving virological success and a higher risk of experiencing virological rebound (AHR 0.63, CI 95% 0.46-0.87, p = 0.004 and AHR 2.52, CI 95% 1.09-5.80, p = 0.030). HBcAb-positive status resulted in a delay in achieving HIV < 50 copies/mL and the appearance of viral rebound in course of cART, hence it is related to a poor control of HIV infection in a population of coinfected patients.

Background: Human herpes virus 8 (HHV8) is the causative agent of Kaposi's sarcoma and has been associated with an increasing number of hematologic diseases such as primary effusion lymphoma (PEL) (both classic and extracavitary form), multicentric Castleman disease and the germinotropic lymphoproliferative disorder. PEL is a rare B cell non-Hodgkin lymphoma that primarily affects immunocompromised patients; aggressive chemotherapy and antiretroviral therapy (ART) with protease inhibitors have been used, with poor results. We present a case of extracavitary PEL in an HIV-infected patient, regressed after ART initiation., Case Presentation: A 42-year-old male was admitted to the emergency room because of several months of malaise, fever and progressive deterioration of the general conditions. On physical examination soft non-painful subcutaneous masses were palpable at retronuchal, retroauricolar and thoracic regions. HIV serology resulted positive: HIV plasma viremia was 782,270 copies/mL, CD4 103 cells/mL. The excision of one of the masses, metabolically active at a positron emission tomography (PET-CT) scan, revealed an HHV8-related extracavitary PEL. HHV8 plasma viremia was 44,826 copies/mL. ART with tenofovir alafenamide/emtricitabine/dolutegravir was started together with ganciclovir for cytomegalovirus chorioretinitis. The progressive disappearance of the masses was seen after 6 weeks of ART, and a PET-CT scan resulted completely negative at 3 months. After 19 months of ART the patient was in remission of PEL, HIV viremia was undetectable (< 20 copies/mL), CD4 count was 766 cells/mL and HHV8 viremia was undetectable., Conclusions: In this clinical case, the complete regression of PEL has been achieved after the immune recovery, as a consequence of ART introduction, without chemotherapy. It cannot be excluded that ganciclovir, used for the treatment of CMV chorioretinitis, may have contributed to the control of HHV8 replication. Whether to try or not a conservative approach in HIV-infected PEL patients must be carefully evaluated, considering the patient's characteristics and the prognostic factors.

Integrase-strand-transfer inhibitors (INSTIs) are known to rapidly reduce HIV-1 plasma viral load, replication cycles, and new viral integrations, thus potentially limiting viral evolution. Here, we assessed the role of INSTIs on HIV-1 V3 evolution in a cohort of 89 HIV-1-infected individuals starting an INSTI- (N = 41, [dolutegravir: N = 1; elvitegravir: N = 3; raltegravir: N = 37]) or a non-INSTI-based (N = 48) combined antiretroviral therapy (cART), with two plasma RNA V3 genotypic tests available (one before [baseline] and one during cART). V3 sequences were analysed for genetic distance (Tajima-Nei model) and positive selection (dN/dS ratio). Individuals were mainly infected by B subtype (71.9%). Median (interquartile-range, IQR) plasma viral load and CD4 + T cell count at baseline were 4.8 (3.5-5.5) log 10 copies/mL and 207 (67-441) cells/mm 3 , respectively. Genetic distance (median, IQR) between the V3 sequences obtained during cART and those obtained at baseline was 0.04 (0.01-0.07). By considering treatment, genetic distance was significantly lower in INSTI-treated than in non-INSTI-treated individuals (median [IQR]: 0.03[0.01-0.04] vs. 0.05[0.02-0.08], p = 0.026). In line with this, a positive selection (defined as dN/dS ≥ 1) was observed in 36.6% of V3 sequences belonging to the INSTI-treated group and in 56.3% of non-INSTI group (p = 0.05). Multivariable logistic regression confirmed the independent correlation of INSTI-based regimens with a lower probability of both V3 evolution (adjusted odds-ratio: 0.35 [confidence interval (CI) 0.13-0.88], p = 0.027) and positive selection (even if with a trend) (adjusted odds-ratio: 0.46 [CI 0.19-1.11], p = 0.083). Overall, this study suggests a role of INSTI-based regimen in limiting HIV-1 V3 evolution over time. Further studies are required to confirm these findings.

P. jiroveci (Pj) causes a potentially fatal pneumonia in immunocompromised patients and the factors associated with a bad outcome are poorly understood. A retrospective analysis on Pj pneumonia (PjP) cases occurring in Tor Vergata University Hospital, Italy, during the period 2011-2015. The patients' demographic, clinical and radiological characteristics and the Pj genotypes were considered. The study population included 116 patients, 37.9% of whom had haematological malignancy or underwent haematological stem cell transplantation (HSCT), 22.4% had HIV infection, 16.4% had chronic lung diseases (CLD), 7.8% had a solid cancer, and 3.4% underwent a solid organ transplant (SOT). The remaining 12.1% had a miscellaneous other condition. At univariate analysis, being older than 60 years was significantly correlated with a severe PjP (OR [95%CI] 2.52 [0.10-5.76]; p = 0.031) and death (OR [95%CI] 2.44 [1.05-5.70]; p = 0.036), while a previous trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis were significantly associated with a less severe pneumonia (OR[95%CI] 0.35 [0.15-0.84], p = 0.023); moreover, death due to PjP was significantly more frequent in patients with CLD (OR[95%CI] 3.26 [1.17-9.05]; p = 0.019) while, admission to the Infectious Diseases Unit was significantly associated with fewer deaths (OR[95%CI] 0.10 [0.03-0.36], p = 0.002). At multivariate analysis, a better PjP outcome was observed in patients taking TMP/SMX prophylaxis and that were admitted to the Infectious Diseases Unit (OR[95%CI] 0.27 [0.07-1.03], p = 0.055, OR[95%CI] 0.16 [0.05-0.55]; p = 0.004, respectively). In conclusion, in our study population, TMP/SMX prophylaxis and infectious disease specialist approach were variables correlated with a better PjP outcome.

Traditional medicine is often chosen due to its affordability, its familiarity with patient's cultural practices, and its wider access to the local community. Plants play an important role in providing indispensable nutrients, while specific small RNAs can regulate human gene expression in a cross-kingdom manner. The aim of the study was to evaluate the effects of plant-enriched purified extract microRNAs from Moringa oleifera seeds (MO) on the immune response and on HIV infection. Bioinformatic analysis shows that plant microRNAs (p -miRs) from MO belonging to 18 conserved families, including p- miR160h, p -miR166, p- miR482b, p- miR159c, p- miR395d, p- miR2118a, p- miR393a, p- miR167f-3p, and p- miR858b are predicted to target with high affinity BCL2, IL2RA, TNF, and VAV1, all these being involved in the cell cycle, apoptosis, immune response and also in the regulation of HIV pathogenesis. The effects of MO p -miRs transfected into HIV+ PBMCs were analyzed and revealed a decrease in viability associated with an increase of apoptosis; an increase of T helper cells expressing Fas and a decrease of intracellular Bcl2 protein expression. Meanwhile no effects were detected in PBMCs from healthy donors. In CD4+ T cells, transfection significantly reduced cell activation and modified the T cell differentiation, thereby decreasing both central and effector memory cells while increasing terminal effector memory cells. Interestingly, the p -miRs transfection induces a reduction of intracellular HIV p24 protein and a reduction of viral DNA integration. Finally, we evaluated the effect of synthetic (mimic) p -miR858b whose sequence is present in the MO p- miR pool and predicted to target VAV1, a protein involved in HIV-Nef binding. This protein plays a pivotal role in T cell antigen receptor (TCR) signaling, so triggering the activation of various pathways. The transfection of HIV+ PBMCs with the synthetic p- miR858b showed a reduced expression of VAV1 and HIV p24 proteins. Overall, our evidence defines putative mechanisms underlying a supplementary benefit of traditional medicine, alongside current antiretroviral therapy, in managing HIV infection in resource-limited settings where MO remains widely available. [ABSTRACT FROM AUTHOR]