Recreational drugs and STI diagnoses among patients attending an STI/HIV reference clinic in Rome, Italy.

BACKGROUND: An observational study was conducted to assess recreational drug use in association with recent STIs among clients of an STI/HIV reference centre in Rome, Italy. METHODS: Attendees self-compiled a questionnaire concerning sexual behaviours and drug use, including the nine drugs used for sex (amphetamines, poppers, cocaine, ketamine, erectile dysfunction agent (EDA), steroids and the three chemsex drugs, ie, chems: γ-hydroxybutyric acid/γ-butyrolactone, crystal and Mcat). RESULTS: Overall, 703 patients participated, with men who have sex with men (MSM) accounting for 50.4% of the total and 73.2% of HIV-positive patients. Apart from condylomatosis, whose prevalence was higher among females (38.8%) and non-MSM (45.8%) than MSM (14.4%), STIs were more frequent among MSM, particularly syphilis (14.1%), gonorrhoea (4.8%), urethritis (3.4%) and hepatitis A (6.5%). Recreational drug use was significantly more frequent among MSM (39.8% vs 17.6% in females and 22.7% in non-MSM). A total of 26.3% of MSM used at least one of the nine drugs and 5.1% at least one of the three chems. Cocaine (13.3%) and poppers (13.0%) were the most used sex drugs in MSM.The use of any of the nine drugs was associated with being MSM (adjusted OR (AOR): 1.94, 95% CI 1.05 to 3.58), sex with partner contacted online (1.99, 95% CI 1.14 to 3.45), group sex (4.08, 95% CI 2.40 to 6.93) and STI in the last year (1.65, 95% CI 1.05 to 2.61). Use of any of the nine chems among MSM was associated with condomless sex (2.24, 95% CI 1.21 to 4.14), group sex (2.08, 95% CI 1.01 to 4.31) and STI diagnosis in the last year (4.08, 95% CI 2.32 to 7.19). CONCLUSIONS: Our data suggest that recreational drug use is quite common among MSM in Italy. No evidence of association with STI was found among non-MSM and females, where only cannabis and cocaine use was reported. The use of chems is still limited, but cocaine, poppers and EDA are widely used among MSM. Recreational drug use appears associated with high-risk sexual behaviours and a higher risk of STI.

Long-term efficacy of dolutegravir in treatment-experienced subjects failing therapy with HIV-1 integrase strand inhibitor-resistant virus.

OBJECTIVES: This study evaluated the virological efficacy of dolutegravir 50 mg twice daily in 190 HIV-1 failing antiretroviral-experienced patients with previous exposure to first-generation integrase strand transfer inhibitor (INSTI) over a 5 year follow-up using data from clinical practice. PATIENTS AND METHODS: This analysis included HIV-1-infected patients who were ≥18 years of age, treatment experienced, had HIV-1 RNA >50 copies/mL, with INSTI-resistant virus, who started dolutegravir 50 mg twice daily plus optimized background therapy (OBT), recorded in the national prospective database PRESTIGIO (www.progettoprestigio.it). Follow-up accrued from the start of dolutegravir 50 mg twice daily + OBT until virological failure (VF) or dolutegravir discontinuation for any reason or the last treatment visit on dolutegravir 50 mg twice daily treatment. VF was defined by the lack of achievement of HIV-1 RNA <50 copies/mL by 6 months and thereafter, or the occurrence of two consecutive HIV-1 RNA ≥50 copies/mL after achievement of undetectable viral load. RESULTS: The estimated VF probabilities were 17% (95% CI = 12%-24%), 28% (95% CI = 21%-37%), 33% (95% CI = 25%-43%), 39% (95% CI = 29%-51%) and 52% (95% CI = 39%-67%) at 12, 24, 36, 48 and 60 months since baseline, respectively. A higher risk of VF was independently associated with baseline viral load >100000 copies/mL (adjusted HR = 4.73, 95% CI = 1.33-16.78, P = 0.016) and with ≥1 INSTI mutations plus Q148H/K/R/N and the G140S/A/C as compared with other subjects (adjusted HR = 4.18, 95% CI = 1.32-13.23, P = 0.015). CONCLUSIONS: Our data showed a favourable long-term efficacy of dolutegravir 50 mg twice daily in association with OBT in treatment-experienced failing subjects, with INSTI-resistant virus, in the real world. A close monitoring of adherence is crucial for maintenance of virological response in this fragile subgroup of subjects.

Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world.

BACKGROUND: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. OBJECTIVES: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. METHODS: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2 months of DAA treatment. RESULTS: One-hundred and thirty-seven patients were included: 21.2% treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (2D/3D) and 78.8% with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3%) and 3 (10.3%) cases treated with 2D/3D, and 16 (14.8%) and 11 (10.2%) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥93%. In 2D/3D-treated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903 ng/mL (IQR 1387-3983), respectively] (n = 5; P = 0.009), with a 40.9% decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs. CONCLUSIONS: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy.

BACKGROUND: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. METHODS: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA < 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. RESULTS: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged > 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. CONCLUSIONS: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability.

Comparative Evaluation of Subtyping Tools for Surveillance of Newly Emerging HIV-1 Strains.

HIV-1 non-B subtypes/circulating recombinant forms (CRFs) are increasing worldwide. Since subtype identification can be clinically relevant, we assessed the added value in HIV-1 subtyping using updated molecular phylogeny (Mphy) and the performance of routinely used automated tools. Updated Mphy (2015 updated reference sequences), used as a gold standard, was performed to subtype 13,116 HIV-1 protease/reverse transcriptase sequences and then compared with previous Mphy (reference sequences until 2014) and with COMET, REGA, SCUEAL, and Stanford subtyping tools. Updated Mphy classified subtype B as the most prevalent (73.4%), followed by CRF02_AG (7.9%), C (4.6%), F1 (3.4%), A1 (2.2%), G (1.6%), CRF12_BF (1.2%), and other subtypes (5.7%). A 2.3% proportion of sequences were reassigned as different subtypes or CRFs because of misclassification by previous Mphy. Overall, the tool most concordant with updated Mphy was Stanford-v8.1 (95.4%), followed by COMET (93.8%), REGA-v3 (92.5%), Stanford-old (91.1%), and SCUEAL (85.9%). All the tools had a high sensitivity (≥98.0%) and specificity (≥95.7%) for subtype B. Regarding non-B subtypes, Stanford-v8.1 was the best tool for C, D, and F subtypes and for CRFs 01, 02, 06, 11, and 36 (sensitivity, ≥92.6%; specificity, ≥99.1%). A1 and G subtypes were better classified by COMET (92.3%) and REGA-v3 (98.6%), respectively. Our findings confirm Mphy as the gold standard for accurate HIV-1 subtyping, although Stanford-v8.1, occasionally combined with COMET or REGA-v3, represents an effective subtyping approach in clinical settings. Periodic updating of HIV-1 reference sequences is fundamental to improving subtype characterization in the context of an effective epidemiological surveillance of non-B strains.

Reactivation of occult HBV infection in an HIV/HCV Co-infected patient successfully treated with sofosbuvir/ledipasvir: a case report and review of the literature.

BACKGROUND: Reactivation of occult or inactive Hepatitis B virus (HBV) infection during immunosuppressant treatments is well known and widely described in literature. The same observation has been made in Hepatitis C (HCV)-infected patients previously exposed to HBV and treated with interferon-free DAA treatments. Because of common transmission routes, persons may have been exposed to HCV, HBV and HIV, but few cases have been reported in this scenario to date. Frequency of HBV reactivation in HIV/HCV co-infected patients previously exposed to HBV and treated with DAA remains unclear. Herein, we report an episode of HBV reactivation in an HIV/HCV co-infected patient prescribed with sofosbuvir/ledipasvir for HCV. CASE PRESENTATION: The patient is a Caucasian 54-years old female, with HIV/HCV co-infection (genotype 4), and a previous exposure to HBV, documented by negativity of HBsAg and positivity of HBsAb and HBcAb. Her medical history included: myocardial infarct, chronic kidney disease stage 3, chronic obstructive pulmonary disease, and mild pulmonary hypertension. HCV had not been treated with interferon (IFN)-based regimens and liver stiffness was 10.5 KPa (Metavir stage F3) at hepatic elastography. Because of CKD, she was prescribed with a nucleoside reverse transcriptase (NRTI)-sparing regimen including darunavir/ritonavir plus etravirine, and thereafter with sofosbuvir/ledipasvir for 12 weeks. Four weeks after DAA termination, the patient was hospitalized with symptoms of acute hepatitis. Blood tests showed HCV RNA <12 IU/ml, but positivity of HBAg, HBeAg, and of anti-core antibodies (IgM and IgG), while anti-HBs and anti-HBe antibodies were negative. HBV DNA was 6.06 Log10 IU/ml. Entecavir was started obtaining resolution of symptoms, normalization of liver enzymes, as well as reduction of HBV DNA and of quantitative HBV surface antigen. CONCLUSIONS: This case-report highlights the risk of HBV reactivation with interferon-free DAA treatment in HIV/HCV co-infected patients previously exposed to HBV and who have contraindications for treatment with nucleoside/nucleotide reverse transcriptase Inhibitors because of comorbid conditions. In the setting of HIV infection, clinicians prescribing DAA should be aware of this risk, and HBV assessment at treatment start as well as virological monitoring during DAA treatment is recommended. Large epidemiological and virological studies are needed to investigate reactivation of occult HBV infection more in depth.

Inguinal and anorectal Lymphogranuloma Venereum: a case series from a sexually transmitted disease center in Rome, Italy.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted infection caused by L1, L2, L3 serovars of C. trachomatis (CT). Since 2003, LGV cases have been increasing in Europe. Aim of this report is to describe the LGV cases diagnosed in the largest STI center in Rome, Italy, from 2000 to 2016. This report shows that two clinically and epidemiologically different series of cases exist, and that, at present, the ano-rectal LGV represents the clinical variant occurring more frequently among men having sex with men (MSM), particularly those HIV-infected. CASE PRESENTATION: Ten cases of LGV were observed. Three were diagnosed in 2009 in HIV-negative heterosexuals patients that presented the classical genito-ulcerative form with lymphadenopathy. Seven cases were observed in 2015-2016 in HIV-infected MSM, that presented the rectal variant and L2b serovar infection; 4 of these had been misclassified as a chronic bowel disease. Chlamydia infection was confirmed by CT-specific PCR (ompA gene nested PCR), followed by sequence analysis to identify the serovar. All the patients were treated with doxycycline for 3 weeks, obtaining a complete response with healing of both clinical symptoms and dermatological lesions. CONCLUSIONS: Our findings suggest that, in case of persistent rectal symptoms in HIV-infected MSM, LGV should be taken into account and investigated through molecular analyses, in order to achieve a correct diagnosis and management of the patients.

Switching to boosted protease inhibitor plus a second antiretroviral drug (dual therapy) for treatment simplification: a multicenter observational study.

BACKGROUND: Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). METHODS: Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. RESULTS: Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. CONCLUSIONS: In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection.

The aim of this study was to analyze the sensitivity of hepatitis E virus antigen (HEV-Ag) to determine acute E hepatitis. Ninety-four serum samples resulting anti-HEV IgM by DIA.PRO assay were analyzed with Wantai assay to check for HEV-Ag. Thirty samples were anti-HEV IgM positive and HEV-RNA positive, 19 samples harbored genotype 3, whereas 11 samples were genotype 1. Overall, 16% of anti-HEV IgM samples resulted HEV-Ag positive and 33.3% of HEV-RNA positive were also HEV-Ag positive. Among 64 HEV-RNA negative samples, 5 (7.8%) were HEV-Ag positive. The concordance of HEV-RNA and HEV-Ag was low (Cohen's Kappa=0.36). The Bland-Altman plot revealed a low agreement between HEV-RNA viral load and HEV-Ag, confirmed by a not significant Spearman's correlation coefficient (rho=0.137, p>0.05). Moreover, the HEV-Ag showed 100% specificity. In genotype 3f samples with a viral load >800 cp/ml HEV-Ag was positive in 80% of samples, whereas all patients harboring genotype 3e were HEV-Ag-negative irrespective of HEV-RNA viral load. Among genotype 1, HEV-Ag positivity was observed only in 27.7% patients and in all samples the viremia was >2000 cp/ml. These data suggest that anti-HEV IgM positivity represents the main biological marker of hepatitis E acute infection in clinical real life settings in developed countries.

Genotypic Tropism Testing in HIV-1 Proviral DNA Can Provide Useful Information at Low-Level Viremia.

The possibility of performing genotypic tropism testing (GTT) with proviral DNA (pvDNA) even during suppressed viremia would facilitate the use of CCR5 inhibitors as part of switching, simplification, or intensification strategies. Thus, we aimed to evaluate the tropism concordance between plasma RNA and pvDNA samples and to assess which factors could affect possible discrepancies between the two compartments. GTT was performed using both plasma RNA and pvDNA from 55 sample pairs from drug-experienced patients. Potential differences between the two compartments were evaluated by analyzing coreceptor usage and genetic variability. Paired samples were also stratified in three levels of viremia (<50, 51 to 500, and >500 copies/ml). Overall, Geno2Pheno comparisons of false-positive rates in the two compartments showed good correlation (r = 0.72). A high level of concordance in tropism predictions for the two compartments was found (46/55 sample pairs [83.6%]). Among the 9 sample pairs with discordant tropisms, a larger proportion of pvDNA samples harboring CXCR4/dual-mixed-tropic viruses was found, in comparison with plasma RNA samples (88.9% versus 11.1%; P = 0.0034). Discordant samples were characterized by greater genetic variability than were concordant samples. With stratification of the paired samples according to viremia levels, the prevalence of discordant samples decreased with increasing viremia (<50 copies/ml, 21.4%; 51 to 500 copies/ml, 15.4%; >500 copies/ml, 6.7%; P = 0.2). Our findings confirm that prediction of viral tropism using pvDNA is feasible even in low-level viremia and provides useful information for therapy optimization for patients with low or suppressed viremia.

Darunavir-based dual therapy of treatment-experienced HIV-infected patients: analysis from a national multicenter database.

BACKGROUND: We assessed the virological response of dual therapy with DRV/r, plus raltegravir, maraviroc or etravirine, in virological failure patients and in virologically suppressed patients collected in the Italian Antiretroviral Resistance Database (ARCA). MATERIAL AND METHODS: The primary endpoint was the percentage of patients remaining free of virological failure (confirmed >50 copies/mL or any change in the regimen). Subjects had a resistance test and at least one follow-up visit. Observation was censored at last visit under dual therapy and survival analysis and proportional hazard models were used. RESULTS: Sixty-seven percent of the 221 patients started DRV/r with RAL, 20.4 % with ETV, and 12.2 % with MAR; 31.2 % virological failures were observed. At survival analysis, the overall proportion of failure was 29.2 % at 1 year and 33.8 % at 2 years. The proportion of failure was lower in patients starting with undetectable vs. detectable viral load (13.3 and 25.2 % vs. 37.4 and 38.8 % at 1 and 2 years, respectively, p = 0.001 for both analyses) and in patients treated with DRV 600 BID vs. 800 QD (HR: 0.56, 95 % CI: 0.31-0.99, p < 0.05). By regimen, the adjusted proportional model showed no significant difference among the three regimens. A significant lower risk of failure was associated with higher GSS (HIV-DB HR: 0.53, 95 % CI: 0.32-0.88, p = 0.014; Rega 0.60, 0.40-0.88, p < 0.01; ANRS 0.55, 0.34-0.90, p = 0.017), while a higher risk of failure with detectable HIV-RNA (3.02, 1.70-5.72, p < 0.001). CONCLUSIONS: Among experienced patients, the best candidates for dual-therapy regimens including DRV/r are those with undetectable viral load and higher GSS.

Analysis of single-nucleotide polymorphisms (SNPs) in human CYP3A4 and CYP3A5 genes: potential implications for the metabolism of HIV drugs.

BACKGROUND: Drug metabolism via the cytochrome P450 (CYP450) system has emerged as an important determinant in the occurrence of several drug interactions (adverse drug reactions, reduced pharmacological effect, drug toxicities). In particular, CYP3A4 and CYP3A5 (interacting with more than 60% of licensed drugs) exhibit the most individual variations of gene expression, mostly caused by single nucleotide polymorphisms (SNPs) within the regulatory region of the CYP3A4 and CYP3A5 genes which might affect the level of enzyme production.In this study, we sought to improve the performance of sensitive screening for CYP3A polymorphism detection in twenty HIV-1 infected patients undergoing lopinavir/ritonavir (LPV/r) monotherapy. METHODS: The study was performed by an effective, easy and inexpensive home-made Polymerase Chain Reaction Direct Sequencing approach for analyzing CYP3A4 and CYP3A5 genes which can detect both reported and unreported genetic variants potentially associated with altered or decreased functions of CYP3A4 and CYP3A5 proteins. Proportions and tests of association were used. RESULTS: Among the genetic variants considered, CYP3A4*1B (expression of altered function) was only found in 3 patients (15%) and CYP3A5*3 (expression of splicing defect) in 3 other patients (15%). CYP3A5*3 did not appear to be associated with decreased efficacy of LPV/r in any patient, since none of the patients carrying this variant showed virological rebound during LPV/r treatment or low levels of TDM. In contrast, low-level virological rebound was observed in one patient and a low TDM level was found in another; both were carrying CYP3A4*1B. CONCLUSIONS: Our method exhibited an overall efficiency of 100% (DNA amplification and sequencing in our group of patients). This may contribute to producing innovative results for better understanding the inter-genotypic variability in gene coding for CYP3A, and investigating SNPs as biological markers of individual response to drugs requiring metabolism via the cytochrome P450 system.

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients.

BACKGROUND: Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption. METHODS: Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model. RESULTS: Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk. CONCLUSIONS: In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

Radiation recall dermatitis in course of epidemic Kaposi's sarcoma.

Radiation recall dermatitis is an acute, rare skin reaction confined to previously irradiated areas that can be triggered by chemotherapeutic drugs (generally doxorubicin and taxanes), which are administrated after radiotherapy. We describe this case report to discuss the timing of the different choice of treatments of progressive Kaposis's sarcoma (KS) disease. KS, the neoplastic disease associated with HHV-8 infection, is still the most commonly diagnosed malignancy in HIV-1 patients, even if its incidence dramatically declined in the highly active antiretroviral therapy (HAART) era. The cutaneous form of disease generally improves with HAART alone or in association with local treatment (cryotherapy, radiotherapy, intralesion chemotherapy), whereas disseminated and/or progressive disease needs to be treated with systemic chemotherapy. In selected patients with progressive disease, systemic and local therapeutic options should be associated. We report a case of a 30-year-old HIV-1-positive man, affected by epidemic cutaneous and mucosal KS, who received several cycles of chemotherapy in succession with radiotherapy and other chemotherapy treatments for disease progression. After 7 months, the end of the last rechallenge with chemotherapy, the patient presented cutaneous painful and ulcerated lesions on the same skin areas previously irradiated.

Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study.

BACKGROUND: Drug-related toxicity has been one of the main causes of antiretroviral treatment discontinuation. However, its determinants are not fully understood. Aim of this study was to investigate predictors of first-line antiretroviral therapy discontinuation due to adverse events and their evolution in recent years. METHODS: Patients starting first-line antiretroviral therapy were retrospectively selected. Primary end-point was the time to discontinuation of therapy due to adverse events, estimating incidence, fitting Kaplan-Meier and multivariable Cox regression models upon clinical/demographic/chemical baseline patients' markers. RESULTS: 1,096 patients were included: 302 discontinuations for adverse events were observed over 1,861 person years of follow-up between 1988 and 2010, corresponding to an incidence (95% CI) of 0.16 (0.14-0.18). By Kaplan-Meier estimation, the probabilities (95% CI) of being free from an adverse event at 90 days, 180 days, one year, two years, and five years were 0.88 (0.86-0.90), 0.85 (0.83-0.87), 0.79 (0.76-0.81), 0.70 (0.67-0.74), 0.55 (0.50-0.61), respectively. The most represented adverse events were gastrointestinal symptoms (28.5%), hematological (13.2%) or metabolic (lipid and glucose metabolism, lipodystrophy) (11.3%) toxicities and hypersensitivity reactions (9.3%). Factors associated with an increased hazard of adverse events were: older age, CDC stage C, female gender, homo/bisexual risk group (vs. heterosexual), HBsAg-positivity. Among drugs, zidovudine, stavudine, zalcitabine, didanosine, full-dose ritonavir, indinavir but also efavirenz (actually recommended for first-line regimens) were associated to an increased hazard of toxicity. Moreover, patients infected by HIV genotype F1 showed a trend for a higher risk of adverse events. CONCLUSIONS: After starting antiretroviral therapy, the probability of remaining free from adverse events seems to decrease over time. Among drugs associated with increased toxicity, only one is currently recommended for first-line regimens but with improved drug formulation. Older age, CDC stage, MSM risk factor and gender are also associated with an increased hazard of toxicity and should be considered when designing a first-line regimen.

Short Communication: HIV Viral Load Trends During the Coronavirus Disease 2019 Pandemic in a Reference Center for HIV in Rome, Italy.

Coronavirus disease 2019 (COVID-19) pandemic has reduced the access of HIV patients to reference centers. However, retention-in-care is critical to maintain adherence to therapy and viral suppression. During lockdown in Italy, our center implemented several measures to ensure HIV-care continuum. To assess whether these efforts were successful, we investigated HIV viral load trend for a 1-year period (September 2019-August 2020), which included lockdown and partial lockdown months in our country. No significant changes overtime in the proportion of undetectable HIV-RNA were observed. Continuity of service made it possible to maintain viral suppression in our patients.

Late Relapse and Reinfection in HCV Patients Treated with Direct-Acting Antiviral (DAA) Drugs.

The risk of hepatitis C virus (HCV) recurrence after direct-acting antiviral (DAA) treatment is <0.5%. However, the distinction between HCV RNA late relapse and reinfection still represents a challenge in virological diagnostics. The aim of this study was to employ next-generation sequencing (NGS) to investigate HCV RNA recurrence in patients achieving a sustained virologic response (SVR) at least six months post-treatment. NGS was performed on plasma samples from six HCV-positive patients (Pt1-6) treated with DAA. NGS of HCV NS5B was analyzed before treatment (T0), after HCV RNA rebound (T1), and, for Pt3, after a second rebound (T2). Reinfection was confirmed for Pt5, and for the first rebound observed in Pt3. Conversely, viral relapse was observed when comparing T0 and T1 for Pt6 and T1 and T2 for Pt3. Z-scores were calculated and used to predict whether HCV-positive patient samples at different time points belonged to the same quasispecies population. A low Z-score of <2.58 confirmed that viral quasispecies detected at T0 and T1 were closely related for both Pt1 and Pt2, while the Z-score for Pt4 was suggestive of possible reinfection. NGS data analyses indicate that the Z-score may be a useful parameter for distinguishing late relapse from reinfection.

Clinical Relevance of Torque Teno Virus (TTV) in HIV/HCV Coinfected and HCV Monoinfected Patients Treated with Direct-Acting Antiviral Therapy.

Torque Teno virus (TTV) is a ubiquitous virus that causes chronic infection in humans with unknown clinical consequences. Here, we investigated the influence of TTV infection on HCV direct-acting antiviral (DAA) efficacy in HIV/HCV coinfected and HCV monoinfected patients as controls. Of 92 study patients, 79.3% were TTV DNA positive; untreated patients exhibited a significantly higher proportion of TTV DNA-positivity vs. sustained virological response (SVR) patients (100.0% vs. 65.2%, p < 0.001), while TTV positivity was not significant in DAA failure patients vs. SVR patients despite HIV/HCV coinfection. TTV DNA viral load was higher among HCV monoinfected patients vs. HIV/HCV coinfected, although marginally significant (p = 0.074) and no significant viral load difference was detected between DAA failures and SVR patients, while untreated vs. SVR patients had a significantly higher viral load (19,884, IQR 5977-333,534, vs. 469, IQR 10-4124, p = 0.004). Alpha-genogroup 3 TTV was the most prevalent genetic group, and no specific strain or genogroup was observed in relapser patients. Among HIV/HCV patients with HCV RNA detectable at end of treatment (EOT), TTV DNA was detected in 9/17 treatment responder patients and 3/5 relapser patients, thus, TTV infection does not appear to influence the control HCV viremia after EOT. Levels of IL-6 IL-4, and CD14 were not significantly different between TTV PCR-positive and -negative patients. These results suggest no association between TTV DNA positivity or viral load and HCV DAA failure whether patients were HIV/HCV coinfected or HCV monoinfected.