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The article discusses an autochthonous dengue outbreak in Rome, Italy, in 2023, detailing the clinical and demographic characteristics of the cases. The outbreak involved three distinct dengue serotypes and affected 19 individuals, with symptoms ranging from fever to skin rash. While hospitalization was recommended for cases with warning signs, all patients eventually recovered without any severe outcomes. The study highlights the importance of early identification and monitoring of dengue cases in non-endemic areas to prevent severe forms of the disease. [Extracted from the article]

Background Lamivudine + dolutegravir maintenance dual therapy (DT) could be less effective than 3-drug therapy (TT) in the context of resistance-associated mutations to nucleoside reverse transcriptase inhibitors (NRTIs). The ARCA database was queried to test this hypothesis with a trial emulation strategy. Methods People with HIV taking 2 NRTIs plus a protease inhibitor or a non-NRTI who switched to DT or dolutegravir-based TT were followed up from the first HIV RNA <50 copies/mL (baseline) to virologic failure (VF; ie, 2 consecutive HIV RNA ≥50 copies/mL or 1 HIV RNA ≥200 copies/mL). Those switching to DT within 6 months were assigned to the treatment arm and all other patients to the control arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. Using inverse probability of censoring weight Cox regression models, we calculated hazard ratios of VF for DT vs TT stratified for the presence of resistance-associated mutations. Results Overall 626 people were analyzed: 204 with DT and 422 with TT (73% men; mean age, 44 years). Ten and 31 VFs occurred with DT and TT, respectively, over a median 5.8 years. When compared with a fully active TT, the DT had similar efficacy (adjusted hazard ratio, 0.88; 95% CI,.29–2.61; P =.812) when full susceptibility was confirmed at historical genotype. When previous M184V/I was present in both groups, the risk of VF was higher for DT vs TT but was not statistically significant (adjusted hazard ratio, 3.06; 95% CI,.45–20.84; P =.252). Conclusions DT was not associated with a significantly higher risk of VF than dolutegravir-based TT. [ABSTRACT FROM AUTHOR]

Background To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%–3.81%; interventional: 0.00%) and without (real-world: 0.73%–2.37%). Meta-analysis–estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00–.04], 0.03 [.01–.06], and 0.04 [.01–.07]; interventional: 0.00 [.00–.02], 0.00 [.00–.01], and 0.00 [.00–.03]) and without (real-world: 0.00 [.00–.02], 0.02 [.01–.04], and 0.02 [.00–.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options. [ABSTRACT FROM AUTHOR]

This article discusses the use of a two-drug antiretroviral therapy (ART) regimen for treatment-naive individuals living with HIV. The authors highlight the hesitation among clinicians to prescribe this regimen, despite its efficacy and potential benefits. The study conducted at a university hospital in Rome, Italy, analyzed the outcomes of patients who met the criteria for initiating a two-drug regimen with lamivudine/dolutegravir. The results showed that the two-drug regimen was well-tolerated and had comparable virological efficacy to a three-drug regimen. Additionally, the two-drug regimen had a lower rate of treatment discontinuation and a higher probability of maintaining the first-line regimen. The authors emphasize the importance of bridging the gap between guidelines and clinical practice to increase the prescription rate of the two-drug regimen. [Extracted from the article]

Background Blood telomere length (BTL) is a validated biomarker of aging. ART reduces immunosenescence and has benefits in terms of BTL in people living with HIV (PLWH). However, it has also been observed that ART containing NRTIs, such as tenofovir or abacavir, which are potent inhibitors of human telomerase activity in vitro , might negatively affect BTL. Here we investigated the effects on BTL 1 year after switching to a dual therapy (DT) with dolutegravir + lamivudine versus maintaining a standard triple therapy (TT) with a two-NRTI backbone and an anchor drug. Methods This was a longitudinal, prospective, matched, controlled study that included virologically suppressed adults on stable three-drug ART who either switched at baseline (BL) to DT or maintained TT. The DT and TT groups were 1:1 matched for age, sex, years since HIV diagnosis, years on ART and anchor drug. BTL was assessed by a monochrome multiplex qPCR at BL and after 48 weeks (W48). Results We enrolled 120 PLWH, i.e. 60 participants in each group. At BL, the BTL means were comparable between the two groups (P  = 0.973). At W48, viro-immunological status was stable and an overall increase in the mean BTL was observed, i.e. +0.161 (95%CI, 0.054–0.268) (P  = 0.004). However, the within-group analysis showed a significant mean BTL gain in the DT group (P  = 0.003) but not in the TT group (P  = 0.656). Conclusions In this setting of virologically suppressed PLWH, simplifying to dolutegravir + lamivudine was associated with a higher gain in BTL than maintaining triple therapy after the 1 year follow-up. These findings suggest that as a simplification strategy dolutegravir + lamivudine might have a positive effect on BTL. [ABSTRACT FROM AUTHOR]

Deep salvage therapy using lopinavir/ritonavir with amprenavir is safe and shows partial virologic inhibition and good immunologic efficacy. Pharmacokinetics enhancement of amprenavir with ritonavir shows increase drug levels above the susceptibility threshold of several resistant viral strains as well as allows a reduction of the pill burden.

To the Editor, Since May 2022, numerous nonendemic countries reported local outbreaks, mostly among men-who-have-sex-with-men (MSM), with a probable human-to-human transmission through close and prolonged interpersonal contact.[[1], [3]] Past reports have described occasional severe complications, but no major complications have been reported in this outbreak as the disease remains self-limiting with fever, lymphadenitis, and a pustular rash not seldom complicated by bacterial superinfections.[[4], [6], [8]] A medical history of vaccination against smallpox has been shown to be effective in preventing monkeypox (MPX) in African outbreaks but it is not clear whether it reduces the risk of human-to-human transmission and its influence on clinical manifestations.[9] As smallpox has been declared eradicated in 1980, most vaccination programs are dated at least over 30 years.[10] In this study, we report six cases of patients, with a documented history of vaccination against smallpox, who were diagnosed with MPX in two Italian clinical centers between May and July 2022. Two of them (Patient 1 and Patient 4) have HIV infection in highly active antiretroviral therapy (HAART) with suppressed viraemia and CD4+ count respectively of 514 and 511 cp/ml. [Extracted from the article]

The TANGO trial demonstrated the efficacy of lamivudine plus dolutegravir in virologically suppressed patients without previous virological failures (VFs). In this dataset from clinical practice investigating the impact of past nucleoside reverse-transcriptase inhibitor resistance on this strategy, the combination of M184V/I plus at least 1 thymidine analog-associated mutation significantly increased the risk of VF. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

We read with interest the work by D'arminio Monforte I et al. i ,[1] evaluating the long-term risk of treatment failure of dolutegravir-based regimens. In our cohort, 887 (22.4%) started dolutegravir as part of a first-line regimen; among the 77.6% of our population that started dolutegravir as treatment-experienced, median time of antiviral therapy (ARV) exposure was 10.2 years (IQR 3.2-18.9) and 1484 (48.3% of experienced PLWHIV) had at least one previous VF. At a multivariate analysis, among treatment-experienced PLWHIV, a previous VF was a predictor of failing during treatment with dolutegravir (aHR 3.47, 95% CI 2.54-4.74, I P i < 0.001), whereas a longer time since ARV initiation inversely correlated with VF (aHR 0.96, 95% CI 0.93-0.98, I P i = 0.003). [Extracted from the article]

Background: HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods: We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure. Results: The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards. Conclusions: GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART. [ABSTRACT FROM AUTHOR]

Objectives: To test retrospectively the ability of four freely available rules-based expert systems to predict short- and medium-term virological outcome following an antiretroviral treatment switch in pre-treated HIV-1 patients. [ABSTRACT FROM PUBLISHER]

Objectives. To analyze virological and immunological features of AIDS-related progressive multifocal leukoencepalophathy (PML) and their association to disease prognosis. Methods. In HIV-infected patients with virologically confirmed PML, JC virus (JCV) DNA load and levels of Macrophage Chemoattractant Protein (MCP)-1 were determined in cerebrospinal fluid. JCV genotypes, rearrangements and JCV DNA binding sites for cellular transcription factors were analyzed by sequencing the viral VP1 region and regulatory region (RR). Results. 45 patients were analyzed: 60% were exposed to highly active antiretroviral therapy (HAART) after PML and 24% before the disease onset. JCV DNA load in cerebrospinal fluid was a strong predictor of patients survival. Lower levels of JCV DNA in cerebrospinal fluid were associated with the following virologic factors: viral genotype 4 (p = 0.043), more rearrangements in the RR (p = 0.046), duplication of RR block B (p = 0.028), and duplication of binding sites for cellular transcription factor NF-1 (p = 0.060). In patients with prior antiretroviral exposure there was a trend towards a higher number of binding sites for cellular transcription factors (p = 0.068). Lower JCV load was also predicted by exposure to HAART (p = 0.010), higher baseline CD4 counts (p = 0.009) and higher cerebrospinal fluid MCP-1 levels (p = 0.036). In a multiple regression model, MCP-1 levels were independently associated with JCV load. Conclusion. HAART leads to a partial immune-mediated control of JCV replication; the virus may tend to escape through the selection of rearrangements in the RR, some associated with enhanced viral replication efficiency, other resulting in multiplication of binding sites for cellular transcription factors. [ABSTRACT FROM AUTHOR]

Background. It is not well defined whether concentration-controlled intervention (CCI) and rules-based human immunodeficiency virus (HIV) type 1 genotype drug-resistance interpretation (GI) or virtual phenotype drug-resistance interpretation (VPI) may improve the outcome of HIV salvage therapy. Methods. In a prospective, randomized, controlled trial, patients were randomized (on a factorial basis) to change treatment after either GI or VPI, and they then were further randomized to the control arm (no CCI) or the CCI arm. Protease inhibitor (P1) and nonnucleoside reverse-transcriptase inhibitor (NNRTI) trough concen- tration (Ctrough) values were determined at weeks 1, 4, 12, and 24 of the study. Results. Among 230 patients, virological benefit (defined by an HIV RNA load of <400 copies/mL at week 24) was not statistically different, either between patients in the GI and VPI arms or between patients in the CCI and control arms. A virological benefit was found for patients in the CCI arm, compared with patients in the control arm, but this benefit was not statistically significant (56.8% vs. 64.3% at week 4 and 63.6% vs. 74% at week 12). Dosage adaptation was possible for only a fraction of patients, because of low rates of treatment adherence or patient refusal to increase dosages. In the logistic regression analysis, independent predictors of virological response at week 24 were a P1 Ctrough value and/or an NNRTI Ctrouth value in the higher quartiles (or above cutoff levels) and a low number of PIs previously received. Moreover, receipt of a regimen that contained PIs boosted with ritonavir was an independent predictor of virological response. Conclusions. The present study did not support the routine use of CCI for patients undergoing salvage treatment, probably as a result of existing difficulties associated with its clinical application. However, a higher Ctrough value appeared to be correlated with treatment response. No major differences were found between VPI or GI when they are used together with expert advice for the selection of salvage treatment combinations. [ABSTRACT FROM AUTHOR]