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.
Hepatitis C virus (HCV) is the cause of more than three-quarters of liver-related deaths in HIV-seropositive individuals and it is remarkable that today approximately one-quarter of HIV-infected ...individuals in Europe and the USA have a HCV coinfection. HIV/HCV coinfected patients were more likely to develop cirrhosis, had an increased risk of developing AIDS, of HIV-related disease and of overall mortality. How HCV may affect the course of HIV infection is not well known even if it was suggested that HCV co-infection is able to increase immune activation and to sensitize CD4+ T-cells towards apoptosis in the absence of HIV therapy. There are many evidences that the simultaneous presence of HIV infection accelerates the liver damage from HCV favouring the evolution to cirrhosis in co-infected patients. HIV increasing of TNF alpha liver production and of HCV replication in peripheral blood lymphomonocytes are the mechanisms at the basis of this phenomenon. HAART had a positive effect on HIV/HCV co-infection, otherwise it does not appear to fully correct the adverse effect of HIV infection on HCV-related outcomes. Traditional treatment with pegilated Interferon plus ribavirin have low rates of sustained virological response in co-infected patients especially if infected with HCV genotype 1, and better results were often obtained in patients in which the use of antiretroviral treatment was avoided to reduce the occurrence of adverse effects. The recent preliminary results on the use of anti-HCV protease inhibitor drugs, boceprevir and telapravir, in co-infected people seems to demonstrate an enhanced antiviral efficacy in the HIV/HCV co-infected population of triple anti-HCV treatment even is some important limitation as interactions with antiretroviral agents and selection of HCV drug resistance, lead to consider the need for further studies designed to assess the best therapeutic strategies.
Since the advent of antiretroviral therapy (ART), morbidity and mortality rates in those infected with human immunodeficiency virus type 1 (HIV-1) have been significantly reduced. However, HIV-1 is ...known to persist in several types of cells and tissues, and will usually return to pretreatment levels when therapy is stopped, even in those individuals who have been on suppressive ART for a long time. The discovery of drug sanctuaries and viral reservoirs in the body, in which HIV may persist, has helped to explain why therapeutic eradication of HIV-1 has proved so difficult. Several studies have indicated that the latent reservoir is an archive, composed of a mixture of wild-type and drug-resistant strains. Archived variants are assumed to remain life-long, thereby precluding the successful recycling of any drug towards which resistance has arisen. Several studies have underlined the value of pro-viral DNA as an additional source of information on the total burden of resistance in an individual. The HIV mutation patterns detected in plasma do not necessarily reflect those found in the cell-associated compartment, and may not be the same as those in different anatomical compartments. Although assessment of drug resistance in plasma is of direct and immediate importance for treatment, examination of the genotypic pattern of HIV-1 in cellular compartments might also provide information allowing a more sustainable response to therapy and better disease management.
The presence of thyroglobulin (Tg) in needle washouts of fine needle aspiration biopsy (Tg-FNAB) in neck lymph nodes (LNs) suspected of metastasis has become a cornerstone in the follow-up of ...patients with papillary thyroid carcinoma (PTC). However, there are limited data regarding the measurement of anti-Tg antibodies in these washouts (TgAb-FNAB), and it is not clear whether these antibodies interfere with the assessment of Tg-FNAB or whether there are other factors that would more consistently justify the finding of low Tg-FNAB in metastatic LNs.
We investigated 232 FNAB samples obtained from suspicious neck LNs of 144 PTC patients. These samples were divided according to the patient's serum TgAb status: sTgAb- (n = 203 samples) and sTgAb+ (n = 29). The TgAb-FNAB levels were measured using two different assays. Tg-FNAB was also measured using two assays when low levels (< 10 ng/mL) were identified in the first assay of the metastatic LNs from the sTgAb+ samples.
The TgAb-FNAB results were negative in both assays in all samples. Low levels of Tg-FNAB were identified in 11/16 of the metastatic LNs of the sTgAb+ patients and 16/63 of the sTgAb- patients (p < 0.05) using assay 1. The measurement of the Tg-FNAB levels using assay 2 indicated additional metastases in 5 LNs of the sTgAb+ patients.
Factors other than the presence of TgAb-FNAB may contribute to the higher number of metastatic LNs with undetectable Tg-FNAB in the sTgAb+ group. In addition, the measurement of Tg-FNAB using different assays was useful to enhance the diagnosis of metastatic LNs, particularly when cytological and Tg-FNAB results are discordant.
This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen.
NS3 protease ...sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays.
Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA >3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11).
HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: a correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI.
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.
PDF
