The clinical manifestations of recent syphilis can be variable, with typical and atypical patterns. Several conditions may cause atypical clinical aspects, including human immunodeficiency virus ...(HIV) co-infection. Besides the clinical features, co-infections may completely alter syphilis serological tests, causing interpretative difficulties and diagnostic delays. Aim of the work is to describe the difficulties encountered during the diagnostic evaluation of atypical skin manifestations and of the serology for syphilis of an HIV-infected patient who had contracted it several times. Nowadays, syphilis may present with atypical clinical and serological features. Physicians should be aware of these possible alterations and consider syphilis even in case of uncommon clinical aspect and unclear serological tests. Cutaneous biopsy and immunohistochemical exam may be mandatory for the diagnosis.
Objectives
Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver ...stiffness and in serum liver fibrosis scores in HIV/HCV‐coinfected patients before and after treatment with direct‐acting antivirals (DAAs).
Methods
Liver stiffness measured using transient elastography as well as serum liver fibrosis scores fibrosis‐4 (FIB‐4) score and the aspartate aminotransferase to platelet ratio index (APRI) were evaluated before and at 6–12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used.
Results
A total of 78 HIV/HCV‐coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline 16.8 (interquartile range (IQR) 10.2–27.0) kPa at baseline vs. 9.4 (IQR 6.7–15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB‐4 score 2.8 (IQR 1.5–4.8) vs. 2.0 (IQR 1.3–3.2), respectively; P < 0.01 and APRI 0.9 (IQR 0.5–2.2) vs. 0.4 (IQR 0.2–0.7), respectively; P < 0.01 was found. In univariate analysis, liver stiffness decrease was associated with increasing age, ‘other’ HCV genotype (vs. G1), the presence of cirrhosis, higher pre‐DAA liver stiffness, sofosbuvir‐based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB‐4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA.
Conclusions
A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV‐coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow‐up.
To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, ...by considering pre-existent resistance (pRes).
pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated.
Three hundred and nine patients were analysed; 5.8% of them showed resistance to both NRTIs and NNRTIs, while 12.6% showed resistance to only one of these drug classes. By 72 weeks, the probability of VR was 11.3%. A higher probability of VR was found in the following groups: (i) patients with NRTI + NNRTI pRes compared with those harbouring NRTI or NNRTI pRes and with those without reverse transcriptase inhibitor pRes (39.2% versus 11.5% versus 9.4%, P < 0.0001); (ii) patients with a virus with full/intermediate resistance to both tenofovir/emtricitabine and rilpivirine compared with those having a virus with full/intermediate resistance to tenofovir/emtricitabine or rilpivirine and those having a virus fully susceptible to TDF/FTC/RPV (36.4% versus 17.8% versus 9.7%, P < 0.001); and (iii) patients with pre-therapy viraemia >500 000 copies/mL compared with those with lower viraemia levels (>500 000: 16.0%; 100 000-500 000: 9.3%; <100 000 copies/mL: 4.8%, P = 0.009). pRes and pre-therapy viraemia >500 000 copies/mL were independent predictors of VR by multivariable Cox regression.
TDF/FTC/RPV as a treatment simplification strategy shows a very high rate of VS maintenance. The presence of pRes to both NRTIs and NNRTIs and a pre-therapy viraemia >500 000 copies/mL are associated with an increased risk of VR, highlighting the need for an accurate selection of patients before simplification.
Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been ...explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4+ T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4+ trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183–343) versus TDF/FTC group: 199 (125–285); Mann–Whitney U-test: p 0.033). A significant 48-week increase of CCR5+ CD4+ T cells and CD4+ effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4+ T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.
Objectives
We evaluated the virological response in patients starting a regimen based on darunavir/ritonavir (DRV/r), which is currently the most widely used ritonavir‐boosted protease inhibitor.
...Methods
Data from 206 drug‐naïve and 327 PI‐experienced patients starting DRV/r 600/100 mg twice daily (DRV600) or 800/100 mg once daily (DRV800) were examined. The probabilities of virological success (VS) and virological rebound (VR) were evaluated in survival analyses. Baseline DRV/r resistance and its evolution at failure were also examined.
Results
DRV600 was preferentially administered in patients with complex requirements (older age, higher viraemia, lower CD4 cell count and DRV/PI resistance) compared with DRV800. By 12 months, the probability of achieving VS was 93.2% and 84.3% in drug‐naïve and PI‐experienced patients, respectively. The higher the baseline viraemia, the longer was the time required to achieve VS, both in drug‐naïve patients >500 000 HIV‐1 RNA copies/mL: median interquartile range (IQR) 6.1 (5.1–10.3) months; 100 000–500 000 copies/mL: median (IQR) 4.9 (3.8–6.1) months; <100 000 copies/mL: median (IQR) 3.9 (3.5–4.8) months; P < 0.001 and in PI‐experienced patients ≥100 000 copies/mL: median (IQR) 7.2 (5.7–11.6) months; <100 000 copies/mL: median (IQR) 2.8 (2.4–3.3) months; P < 0.001. In PI‐experienced patients, the probability of VR was higher for higher viraemia levels (22.3% for ≥100 000 copies/ml vs. 9.7% for <100 000 copies/mL; P = 0.007). Baseline resistance did not affect the virological response. At failure, a high percentage of patients maintained virus susceptible to all PIs (drug‐naïve: 95%; PI‐experienced: 80%). Despite being used more often in patients with more complex requirements, DRV600 performed as well as DRV800.
Conclusions
In clinical practice, use of DRV/r (with its flexible dosage) results in high rates of virological response. These data support the use of PI/r in patients whose characteristics require potent drugs with a high genetic barrier.
Objectives
Despite not being approved in Europe as first‐line therapy, the efavirenz (EFV)‐containing single tablet regimen (STR) is frequently used in clinical practice in naïve patients but few ...data are available on this strategy. In our study, we aimed to assess the risk of EFV discontinuation in patients starting antiretroviral therapy with STR vs. nonSTR.
Methods
This was a multicentre study retrospectively enrolling naïve patients starting EFV+TDF+FTC. Patients were followed from the time of treatment initiation to the discontinuation of the EFV‐containing regimen, comparing STR vs. nonSTR. Two different analyses were performed: (A) nonSTR patients censored at the last observation (switch to STR not considered as the end of observation); (B) nonSTR patients censored at the time of switch to STR.
Results
The study included 235 patients, of whom 74 (31.5%) directly started STR. Among patients starting nonSTR, 108 (67.1%) switched to STR after a median period of 6 months. Forty‐four EFV discontinuations were observed (13 among STR vs. 31 among nonSTR patients). The overall estimated probability of discontinuation was 30% at 5 years, about half (14.8%) of these occurring during the first year. Analysis A did not show significant differences between STR and nonSTR regarding the probability of efavirenz discontinuation (19.9% vs. 24.7% at 5 years, P = 0.630). In contrast, Analysis B showed that the probability of EFV discontinuation was similar (8.3%) between STR and nonSTR patients up to 8 months. Thereafter, a significantly higher rate of discontinuation was observed in nonSTR patients (47.5% vs. 19.9% at 5 years, P = 0.034).
Conclusions
Our data suggest that an early switch to STR during the first months of treatment could reduce the risk of EFV discontinuation.
Introduction
This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of ...treatment-experienced human immunodeficiency virus (HIV) patients.
Results
Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials.
Discussion
The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected.
Conclusion
The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.
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