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OBJECTIVES: To assess the impact of switching to dolutegravir plus lamivudine maintenance therapy on the HIV cellular reservoir size. PATIENTS AND METHODS: This was a prospective, longitudinal, matched, controlled study. We enrolled virologically suppressed patients on stable three-drug ART who switched at baseline (BL) to dolutegravir/lamivudine (DT group) or maintained triple therapy (TT group); subjects in the TT group were matched 1:1 with those in the DT group according to age, gender, years since HIV diagnosis, years on ART and anchor drug. Total blood-associated HIV DNA levels were assessed by droplet digital PCR at BL and after 48 weeks (T48). Results were expressed as log10 HIV DNA copies/106 leucocytes. RESULTS: We enrolled 40 patients in the DT group and 40 in the TT group; the two groups were homogeneous for all main characteristics except nadir CD4 cell count. At BL, HIV DNA levels were comparable between the DT and TT groups: 2.27 (IQR 1.97-2.47) and 2.26 (IQR 2.05-2.61) log10 HIV DNA copies/106 leucocytes, respectively. Change in HIV DNA load from BL to T48 was -0.105 (IQR -0.384 to 0.121, P = 0.041) in the DT group and -0.132 (IQR -0.362 to 0.046, P = 0.005) in the TT group, with a comparable decline observed between the two groups (P = 0.821). A higher HIV DNA decline was associated with higher BL CD4/CD8 ratio. CONCLUSIONS: Maintenance therapy with dolutegravir/lamivudine had the same impact as the triple regimen on HIV DNA levels after 48 weeks of treatment. These data seem to support the effectiveness of a dolutegravir/lamivudine dual regimen in controlling the magnitude of the cellular reservoir (www.clinicaltrials.gov, number NCT02836782).
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/uso terapêutico , DNA , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Lamivudina/uso terapêutico , Oxazinas , Piperazinas/uso terapêutico , Estudos Prospectivos , Piridonas , Carga ViralRESUMO
BACKGROUND: Direct comparisons between lamivudine plus bPIs and lamivudine plus dolutegravir as maintenance strategies in virologically-suppressed HIV positive patients are lacking. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) were compared in a cohort of HIV+ patients on a virologically-effective ART starting lamivudine with either darunavir/r, atazanavir/r or dolutegravir. Changes in laboratory parameters were also evaluated. RESULTS: Four-hundred-ninety-four patients were analyzed (170 switching to darunavir/r, 141 to atazanavir/r, 183 to dolutegravir): median age was 49 years, with 8 years since ART start. Groups differed for age, HIV-risk factor, time since HIV-diagnosis and on ART, previous therapy and reasons for switching. Estimated proportions free from TD at week 48 and 96 were 79.8 and 48.3% of patients with darunavir/r, 87.0 and 70.9% with atazanavir/r, and 88.2 and 82.6% with dolutegravir, respectively (p < 0.001). Calendar years, HIV-risk factor, higher baseline cholesterol and an InSTI-based previous regimen predicted TD, whereas lamivudine+dolutegravir therapy and previous tenofovir use were protective. VF was the cause of TD in 6/123 cases with darunavir/r, 4/97 with atazanavir/r and 3/21 with dolutegravir. Other main reasons for TD were: toxicity (43.1% with darunavir/r, 39.2% with atazanavir/r, 52.4% with dolutegravir), further simplification (36.6% with darunavir/r, 30.9% with atazanavir/r, 14.3% with dolutegravir). Incidence of VF did not differ among study groups (p = 0.747). No factor could predict VF. Lipid profile improved in the dolutegravir group, whereas renal function improved in the bPIs groups. CONCLUSIONS: In real practice, a switch to lamivudine+dolutegravir showed similar efficacy but longer durability than a switch to lamivudine+bPIs.
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Soropositividade para HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Carga Viral/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Sulfato de Atazanavir/uso terapêutico , Estudos de Coortes , Darunavir/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Soropositividade para HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Estudos Retrospectivos , Ritonavir/uso terapêutico , Tenofovir/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To compare mucosal flora in HIV-positive and HIV-negative subjects, to assess chemosusceptibility patterns of carriage isolates and to evaluate possible predisposing factors within the two groups. METHODS: We analyzed microbes isolated from nasopharyngeal swabs in virologically suppressed and immunologically stable HIV-positive adult outpatients (n=105) at baseline and after 12 months and in an age-matched cohort of HIV-negative outpatients (n=100) at baseline. Bacteria and Candida spp strains were isolated and identified through standard biochemical assays and chemosusceptibility tests were performed. Multi Locus Sequence Typing was also determined to characterize Staphylococcus aureus isolates from HIV-infected persistent carriers. RESULTS: In HIV-positive patients a significantly higher rate of colonization by S. aureus as compared to HIV-negative controls was observed (19% vs 8%, p=0.02), with a relevant percentage of penicillin resistant strains (15% vs 0, p=0.24). Methicillin resistant strains were recovered only from HIV-positive subjects. Overall HIV-positive status was the only predictor of S. aureus colonization (OR 2.77, 95% CI 1.03;7.41, p=0.04). CONCLUSIONS: The nasopharyngeal bacterial flora differs between HIV-positive and HIV-negative subjects and appears relevant for possible development of staphylococcal infections in HIV-positive patients.
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Fenômenos Fisiológicos Bacterianos , Candida/fisiologia , Infecções por HIV , Infecções Estafilocócicas , Adulto , Antibacterianos , Bactérias/crescimento & desenvolvimento , Portador Sadio , HIV , Infecções por HIV/complicações , Infecções por HIV/microbiologia , Humanos , Tipagem de Sequências Multilocus , Nariz/microbiologia , Infecções Estafilocócicas/complicaçõesRESUMO
Background: Biomarkers of systemic inflammation predict non-AIDS events and overall mortality in virologically suppressed HIV-1-infected patients. Objectives: To determine whether switching to a dual antiretroviral maintenance therapy was associated with modification of biomarkers of systemic inflammation as compared with continuation of successful standard triple therapy. Methods: In this substudy of the randomized ATLAS-M trial, we compared in virologically suppressed patients the impact at 1 year of simplification to a dual therapy with atazanavir/ritonavir plus lamivudine versus maintaining atazanavir/ritonavir plus two NRTI triple therapy on markers of systemic inflammation. Plasma levels of interleukin-6, C-reactive protein (CRP), soluble CD14 (sCD14) and D-dimer were quantified by ELISA at baseline and at 48 weeks. Results: A subset of 139 of 266 randomized patients with available samples was analysed: 69 in the triple therapy arm and 70 in the dual therapy arm. The baseline biomarker levels were comparable between randomization arms. No significant differences in changes from baseline to week 48 were observed between arms (dual therapy versus triple therapy): IL-6, -0.030 versus -0.016 log10 pg/L; CRP, +0.022 versus +0.027 log10 pg/mL; sCD14, -0.016 versus +0.019 log10 pg/mL; and D-dimer, -0.031 versus +0.004 log10 pg/mL. A history of cancer was associated with higher baseline levels of IL-6 (P = 0.002) and CRP (P = 0.049). No relationship was observed between baseline biomarker level and persistent residual viraemia, HIV-1 DNA load, plasma lipids and other potential explanatory variables. Conclusions: Simplification with atazanavir/ritonavir plus lamivudine does not affect plasma markers of systemic inflammation in virologically suppressed patients. The association between these findings and clinical outcomes requires further evaluation.
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Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Inflamação/sangue , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , Infecções por HIV/mortalidade , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral/efeitos dos fármacosRESUMO
Objectives: The AtLaS-M randomized trial showed that in patients with HIV-1 RNA <50 copies/mL on atazanavir/ritonavir + two NRTIs, switching to a dual therapy with atazanavir/ritonavir+lamivudine had superior efficacy as compared with continuing the previous triple therapy. This substudy was designed to evaluate at 48 weeks the impact of the dual therapy versus the three-drug atazanavir/ritonavir-based therapy on the HIV-1 cellular reservoir as reflected by the quantification of blood-associated HIV-1 DNA levels. Methods: In a representative subset of 201 of 266 randomized patients (104 in the dual-therapy arm and 97 in the triple-therapy arm) total HIV-1 DNA levels in whole blood at baseline and after 48 weeks and factors associated with the HIV-1 DNA levels were evaluated. Results: The mean baseline HIV-1 DNA levels (2.47 log 10 copies/10 6 leucocytes) were comparable between arms. A significant mean decrease between baseline and week 48 was observed: -0.069 log 10 copies/10 6 leucocytes in the dual-therapy arm ( P = 0.046) and -0.078 in the triple-therapy arm ( P = 0.011); the mean difference between arms was -0.009 ( P = 0.842). Nadir CD4 count was inversely correlated with baseline HIV-1 DNA ( P = 0.009); longer duration of ART and lower nadir CD4 correlated with a less prominent HIV-1 DNA decrease (both P < 0.005). Higher baseline HIV-1 DNA was associated with residual viraemia at week 48 ( P = 0.031). Conclusions: When compared with continuing three-drug therapy, atazanavir/ritonavir+lamivudine dual therapy resulted in a similar decline in HIV-1 DNA levels in patients with sustained virological suppression. These data support the safety of this simplified treatment strategy in terms of its effect on the cellular HIV-1 reservoir.
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Fármacos Anti-HIV/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir/administração & dosagem , Contagem de Linfócito CD4 , DNA Viral/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Humanos , Lamivudina/administração & dosagem , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico , Ritonavir/administração & dosagem , Carga Viral/efeitos dos fármacosRESUMO
The 13-valent pneumococcal conjugate vaccine (PCV-13) is recommended for HIV-infected people, although its effectiveness in this population remains under evaluation. In this study, we describe the development, optimization, and analytical validation of an ELISA procedure to measure specific antibodies for the pneumococcal polysaccharide serotypes included in PCV13 vaccine, testing sera obtained from HIV-infected outpatients (n = 30) who received the vaccine. The protocol followed the last version of WHO guidelines, based on the new standard 007sp, with the modification of employing Statens Serum Institut (SSI) antigens. We supplied the assay performance validation in terms of sensitivity, reproducibility, precision and accuracy. In addition we detailed optimal antigen-coating concentrations and ELISA conditions common to all 13 serotypes, suitable for laboratories performing these assays in order to standardize the method. Our procedure showed reproducibility and reliability, making it a valid alternative for evaluating the response to pneumococcal serotypes included in PCV13 vaccine.
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Anticorpos Antibacterianos , Vacinas Pneumocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Masculino , Vacinas Pneumocócicas/administração & dosagem , Polissacarídeos Bacterianos/administração & dosagem , Sensibilidade e EspecificidadeRESUMO
Objectives: We aimed to assess the immunologic response to BNT162b2 mRNA COVID-19 vaccine in ART-experienced people living with HIV (PLWH). Methods: In this pilot prospective study, we enrolled 20 PLWH (all on effective ART, 80% with CD4 cells count >500) and 52 immunocompetent health-care workers, as control. All subjects received two doses of vaccine 21 days apart. Serum samples were collected at different time points, immediately before first administration (BL) and 21 days after each dose (T1 and T2) and 45-50 days after second dose (T3). We evaluated the immune response in terms of frequency of responders and antibody titers against SARS-CoV-2 at each timepoint. The viro-immunological parameters of PLWH were also monitored. Results: We found that the participants displayed an immune response after the first dose that increased markedly at T2. At T3 a significantly descending trend of IgG levels was observed in both groups. No difference in humoral immune response assessed in terms of percentage of responders after first and second dose and in terms of IgG titers over time and at each time point was found between groups. Any significant variation in terms of viremia and immunological parameters was observed in PLWH. Conclusions: BNT162b2 mRNA COVID-19 vaccine appears immunogenic in this setting of PLWH eliciting an immune response comparable to that of healthy donors.
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Objectives: To evaluate the impact of a treatment switch to dolutegravir plus lamivudine on the soluble inflammatory biomarkers of HIV-infected patients treated in a real-life setting.Materials and methods: This was a longitudinal study that enrolled virologically-suppressed patients on stable 3-drug ART who switched at baseline to dolutegravir + lamivudine (2DR-group), based on the clinician's decision, or maintained triple therapy (3DR-group). Subjects in the 3DR-group were matched with those in the 2DR-group for age, gender and type of anchor drug. Plasma levels of interleukin-6 (IL-6), I-FABP, D-dimer and C-reactive protein (CRP) were quantified by a microfluidic ultrasensitive ELISA assay at baseline and at 48 weeks.Results: Overall 208 subjects were enrolled: 101 in the 2DR-group and 107 in the 3DR-group. At baseline, biomarker levels were comparable between groups. The differences in mean log10 change from baseline to 48 weeks between groups (2DR versus 3DR) were: IL-6 (pg/L) -0.051(95% CI -0.115/0.009) versus 0.004 (95% CI -0.046/0.054) (p = 0.159); I-FABP (pg/mL), -0.088 (95% CI -0.14/-0.041) versus 0.033 (95%CI -0.007/0.072) (p < 0.001); D-dimer (pg/mL), -0.011(95% CI-0.055/0.033) versus -0.021 (95% CI -0.071/0.030) (p = 0.780) and CRP (pg/mL), -0.028 (95%CI -0.118/0.063) versus 0.118 (95% CI 0.024/0.211) (p = 0.028).Conclusions: At 1 year, switching to a dolutegravir plus lamivudine dual regimen in this setting showed a favorable trend for two biomarkers analyzed, i.e., I-FABP and CRP, as compared to continuing a triple therapy. These results add important new data in support of the safety of this approach in terms of its effect on the inflammatory milieu.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Biomarcadores , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Inflamação/tratamento farmacológico , Interleucina-6/farmacologia , Interleucina-6/uso terapêutico , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Estudos Longitudinais , Oxazinas , Piperazinas , Piridonas , Carga ViralRESUMO
Total cell-associated HIV-1 DNA is a surrogate marker of the HIV-1 reservoir, however, certified systems for its quantification are not available. The Italian HIV DNA Network was launched to validate HIV-1 DNA quantification methods in use at University and Hospital labs. A quality control panel including HIV-1 DNA standards, reconstructed blood samples (RBSs) and DNA from different HIV-1 subtypes was blindly tested by 12 participating labs by quantitative real-time PCR (n = 6), droplet digital PCR (n = 3) or both (n = 3). The median 95% hit rate was 4.6 (3.7-5.5) copies per test and linearity in the tested range was excellent (R2 = 1.000 [1.000-1.000]). The median values obtained across labs were 3,370 (2,287-4,245), 445 (299-498), 59 (40-81) and 7 (6-11) HIV-1 DNA copies, for the 3,584, 448, 56 and 7-copy standards, respectively. With RBSs, measured values were within twofold with respect to the median in two thirds of cases. HIV-1 subtypes were missed (CRF01_AE by 3 labs) or underestimated by > 1 log (subtypes A, C, D, F by one lab; CRF01_AE by one lab; CRF02_AG by one lab). The overall performance was excellent with HIV-1 DNA standards, however detection of different HIV-1 subtypes must be improved.
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Infecções por HIV , HIV-1 , Infecções por HIV/diagnóstico , HIV-1/genética , Humanos , Itália , Reação em Cadeia da Polimerase em Tempo RealAssuntos
Sulfato de Atazanavir/uso terapêutico , DNA Viral/sangue , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir/administração & dosagem , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , Humanos , Lamivudina/administração & dosagem , Leucócitos Mononucleares/virologia , Projetos Piloto , Reação em Cadeia da Polimerase , Ritonavir/administração & dosagemRESUMO
The focus of this review is to examine the importance of quantifying total HIV DNA to target the HIV reservoir and the clinical implications and challenges involved in its future application in clinical practice. Despite intrinsic limitations, the quantification of total HIV DNA is currently the most widely used marker for exploring the HIV reservoir. As it allows estimating all forms of HIV DNA in the infected cells, total HIV DNA load is the biomarker of the HIV reservoir that provides most of the insights into HIV pathogenesis. The clinical role of total HIV-DNA in both untreated and treated patients is extensively supported by important lines of evidence. Thus, predictive models that include total HIV DNA load together with other variables could constitute a prognostic tool for use in clinical practice. To date, however, this marker has been primarily used in experimental evaluations. The main challenge is technical. Although the implementation of droplet digital PCR could improve analytical performance over real-time PCR, the lack of standardization has made cross-comparisons of the data difficult. An effort by investigators to compare protocols is needed. Furthermore, the main effort now should be to involve the biomedical industry in the development of certified assays for in vitro diagnostics use.
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BACKGROUND: this study aimed to determine the proportion of people living with HIV (PLWH) with anti-SARS-CoV-2 IgG antibodies in a large sample from a single HIV referral center in Rome, Italy; the time-frame included both the first and the second wave of the Italian COVID-19 pandemic; Methods: we conducted a cross-sectional study on stored cryopreserved samples from 1 March 2020 to 30 November 2020. Total antibodies against SARS-CoV-2 were preliminarily tested using a chemiluminescent immunoassay. Positive results were re-tested with an ELISA assay as an IgG confirmatory test; Results: overall, 1389 samples were analyzed from 1106 PLWH: 69% males, median age 53 years, 94% on antiretroviral treatment, 93% with HIV-RNA < 50 copies/mL, median CD4 cell count 610 cell/µL. Our analysis revealed a total of n = 8 patients who tested IgG positive during the study period. Seroprevalence was equal to 0% in the first months (March-June); this started to increase in July and reached a maximum rate of 1.59% in October 2020. The overall seroprevalence was 0.72% (8/1106, 95% CI 0.37-1.42). CONCLUSION: our findings from this setting show a low IgG SARS-CoV-2 prevalence among PLWH as compared to data available from the general population.
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Currently approved 2-drug therapies are as effective as 3-drug regimens but could potentially lead to increased cancer risk due to less efficient immune recovery. We conducted a longitudinal cohort study in a tertiary Italian hospital to investigate HIV+ patients starting a triple therapy (TT) (2 NRTIs +3rd agent) or a dual therapy (DT) (3TC/FTC+boosted-PI, boosted-DRV+RAL, and 3TC/FTC or RPV+DTG) regimen between 2009 and 2018. The effect of DT (vs. TT) on tumor onset was evaluated by the multivariable Cox regression and the marginal structural Cox model, after estimating the inverse probability of treatment weights (IPTW). One thousand one hundred and seven patients who had a median follow-up of 4.2 person-years (py) were evaluated; 69.2% were males, with a median age of 43 years. Overall 2,513 treatments were started during the study period (479 DT, 2,034 TT). Eight tumors occurred over 965 py with DT and 35 over 3,817 py during TT (p = .797). In the Cox regression, DT did not predict an increased risk of tumor compared with TT (HR 1.14; p = .757) after adjusting for potential confounders. A marginal structural model using IPTW (HR 0.68; p = .328) and stabilized IPTW (HR 0.69; p = .361) confirmed this result. Preliminary findings from our cohort do not suggest an increased risk of tumors with DT compared to TT.
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Fármacos Anti-HIV , Infecções por HIV , Neoplasias , Preparações Farmacêuticas , Adulto , Fármacos Anti-HIV/efeitos adversos , Estudos de Coortes , Infecções por HIV/tratamento farmacológico , Hospitais , Humanos , Itália/epidemiologia , Lamivudina/uso terapêutico , Estudos Longitudinais , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologiaRESUMO
Not available.
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Fármacos Anti-HIV/administração & dosagem , DNA/sangue , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV/genética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Lamivudina/administração & dosagem , Oxazinas/administração & dosagem , Piperazinas/administração & dosagem , Piridonas/administração & dosagem , Adulto , Combinação de Medicamentos , Feminino , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Background: HIV-induced systemic immune activation and inflammation have been associated with morbidity and mortality in virologically suppressed patients.Objective: To evaluate the impact of treatment switch from a dual regimen with lamivudine (3TC) plus ritonavir-boosted protease inhibitors (PI/r) to 3TC plus dolutegravir (DTG) on the monocyte activation marker soluble CD14 (sCD14) and other inflammatory biomarkers, interleukin-6 (IL-6), C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP) and D-dimer.Methods: We performed a retrospective case-crossover study on integrase inhibitors-naïve virologically suppressed patients while on 3TC + PI/r dual maintenance therapy for ≥48 weeks who switched to 3TC + DTG and maintained this regimen for ≥48 weeks. Biomarkers plasma levels were tested by ELISA assays on stored samples at three time points: at switch (BL), 48 weeks before (-48 W) and 48 weeks after switch (+48 W).Results: A total of 67 patients were included. Median sCD14 levels were stable from -48 W to BL (from 6.07 to 6.04 log10 pg/mL, p = 0.235) but showed a statistically significant decrease after switch: from 6.04 (IQR 5.92-6.12) at BL to 5.95 (IQR 5.84-6.07) log10 pg/mL at + W48 (p < 0.001). Concurrently, an improvement in lipid profile was observed, even thought it was not correlated to the change in sCD14. The levels of IL-6, CRP, I-FABP and D-dimer remained stable before and after the switch to 3TC + DTG.Conclusions: In virologically suppressed HIV-infected patients on a 3TC + PI/r dual therapy, switching to 3TC + DTG was associated with a significant decline in sCD14. These data suggest reduced monocyte activation following substitution of boosted PI with DTG, which could have important clinical implications.
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INTRODUCTION: Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated. METHODS: In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection. RESULTS: We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 µg/ml, ≥ 1 µg/ml and ≥ individual serotype-specific correlates of protection was similar between groups. CONCLUSION: In this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02123433.
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Bone toxicity is a well-known side effect of several antiviral agents. In a cohort of virologically suppressed HIV-infected patients, we investigated the effects of a lamivudine/dolutegravir dual therapy on bone mineral density (BMD). We observed a significant improvement in lumbar spine BMD as well as T-score after 12 months of observation with concomitant bisphosphonate therapy independently predicting a greater improvement. These preliminary data show a favorable effect of this 2-drug regimen on bone health.
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Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/farmacologia , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Lamivudina/farmacologia , Lamivudina/uso terapêutico , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxazinas , Piperazinas , Piridonas , Estudos RetrospectivosRESUMO
BACKGROUND: The influence of HIV-1 co-receptor usage on the course of therapy in subjects fully responding to ART has been poorly investigated. OBJECTIVES: To explore the relationship between co-receptor tropism and cellular reservoir size, residual viremia and subsequent virological outcome in ART-treated patients with HIV-1 RNA stable <50 copies/mL. STUDY DESIGN: Viral co-receptor usage was predicted by viral env DNA sequencing with geno2pheno interpretation (FPR20%) and classified as R5 and non-R5. Total blood-associated HIV-1 DNA levels (log10 copies/106 leukocytes) were measured by qRT-PCR (5'LTR). Residual plasma viremia was categorized as detectable (1-49 cps/mL) or undetectable (<1 copy/mL). Virological rebounds (any HIV-1 RNA >50 copies/mL) were evaluated over 96 weeks. RESULTS: The study included 116 subjects. Patients with R5 virus (nâ¯=â¯59) and non-R5 virus (nâ¯=â¯57) were homogeneous for the main characteristics except for the lower nadir CD4 cell count in the non-R5 group. Patients with non-R5 variants showed higher levels of HIV-1 DNA as compared to patients with R5 virus: mean 2.47 (95% CI 2.37-2.56) vs 2.17 (2.08-2.26) (pâ¯<â¯0.001). Moreover, a higher proportion of patients in the non-R5 group displayed detectable residual viremia with respect to the R5-group (54.4% vs 32.2%, pâ¯=â¯.016). Detectable residual viremia was found to be significantly associated with viral rebounds. CONCLUSION: The presence of non-R5 viral DNA variants is related to a higher probability of residual viremia and to a larger size of the cellular viral reservoir in this setting. These data highlight a potential role of viral tropism in the monitoring of HIV-1 infection in virologically controlled subject.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/fisiologia , Carga Viral , Tropismo Viral , Terapia Antirretroviral de Alta Atividade , DNA Viral/sangue , HIV-1/isolamento & purificação , Humanos , Leucócitos/virologia , RNA Viral/sangue , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Resposta Viral Sustentada , Resultado do Tratamento , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
BACKGROUND: The integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. OBJECTIVES: We aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. STUDY DESIGN: Fifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels <40 copies/ml for ≥6 months and CD4 counts >200cells/µl for ≥12 months were enrolled. Thirty-four patients were from the treatment simplification RASTA randomized study switching standard therapy to a raltegravir-based regimen (RASTA group), while 24 continued a PI or NNRTI based-regimen (controls). Residual plasma HIV-1RNA (5-40copies/mL) and HIV-1DNA were assessed at 0, 24 and 48 weeks. RESULTS: At week 0 (W0), HIV-1DNA was detected in all patients while at W48 it was detectable in 82.4% of the RASTA group vs 100% of controls (p=0.03). There was a significant decline of HIV-1DNA at W48 in the RASTA group (mean change from baseline -0.21 [95% CI -0.41; -0.01] log10 copies/106 CD4; p=0.03) but not in controls. Ultrasensitive HIV-1RNA was detectable at baseline in 50% of RASTA group vs 67% of controls and at W48 in 32.4% vs 42%, respectively. No differences were found between HIV-1RNA levels at baseline and W48 within and between groups. CONCLUSIONS: Switching successful therapy to raltegravir-based regimens may be associated with a decrease of the HIV-1 reservoir, as measured by peripheral blood cellular HIV-1DNA levels.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , DNA Viral/sangue , HIV-1/isolamento & purificação , RNA Viral/sangue , Raltegravir Potássico/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Raltegravir Potássico/administração & dosagem , Carga Viral/efeitos dos fármacosRESUMO
OBJECTIVES: Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) versus the 23-valent polysaccharide vaccine (PPSV23) in HIV-infected adults. METHODS: We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/µL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50) received two doses of PCV13 eight weeks apart, and group 2 (n = 50) received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100) were also enrolled as baseline controls. RESULTS: Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group. CONCLUSIONS: In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov NCT02123433.