•In the current multinational outbreak of MPX, ocular complications have been reported very rarely compared with what has been reported in previous outbreaks in endemic settings.•This is one of the ...first cases described of monkeypox (MPX) with ocular involvement with an infective and replication competent MPXV isolated in culture.•The time-course of the ocular manifestations (ocular onset delayed with respect to the skin rash and concomitant systemic symptoms).is suggestive of a pathogenetic mechanism based on self-inoculation from skin lesions.•Viral clearance and clinical recovery after treatment with intravenous Cidofovir were slow.
•The impact of co-infection with SARS-CoV-2 on HIV replication in the central nervous system (CNS) is unknown.•SARS-CoV-2 could alter the permeability of the blood–brain barrier and cause a CNS HIV ...escape.•The few symptoms during coronavirus disease 2019 (COVID-19) suggest a contained inflammatory response in CNS/plasma.•Poor immunological recovery might contribute to soften immune-pathogenetic processes.
We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS.
Abstract
Objectives
To evaluate the prevalence and therapeutic relevance of drug resistance among isolates from ART-experienced HIV-1-infected patients over the past two decades in Italy.
Methods
...Dynamics of resistance to one, two and three or more antiretroviral classes were evaluated from 1999–2018. Virological success (VS) after the latest therapy switch was evaluated according to cumulative class resistance and cumulative genotypic susceptibility score (Stanford HIV_DB algorithm).
Results
Among 13 663 isolates (from 6739 patients), resistance to at least one drug class decreased sharply from 1999 to 2010 (≤2001, 84.6%; 2010, 43.6%; P < 0.001), then remained relatively constant at ∼40% during 2010–18, with the proportion of resistance to three or more classes also stable (∼5%). After 2008, integrase inhibitor resistance slightly increased from 5.6% to 9.7% in 2018 and contributed to resistance, particularly in isolates with resistance to three or more classes (one class, 8.4%; two classes, 15.3%; three or more classes, 34.7%, P < 0.001). Among 1827 failing patients with an available follow-up, by 1 year after genotype-guided therapy start the probability of VS was 87.6%. Patients with cumulative resistance to three or more classes and receiving a poorly active regimen showed the lowest probability (62.6%) of VS (P < 0.001) compared with all other patients (≥81.8%). By Cox regression analysis, cumulative MDR and receiving poorly active antiretroviral regimens were associated with a lower hazard of VS compared with those without resistance.
Conclusions
A dramatic drop of HIV-1 drug resistance at failure has been achieved over the last two decades in Italy; resistance to three or more classes is low but present among currently failing patients. Its management still requires a rational and careful diagnostic and therapeutic approach.
Heparin‐binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk ...of progressing to active disease. Few data are available in immune‐compromised patients, which are those with increased risk of TB reactivation. The aim of this stusy was to evaluate the immune response to HBHA in HIV‐infected subjects with LTBI (HIV‐LTBI) or active TB (HIV‐TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens. The responses are evaluated in relation to TB status and in the LTBI subjects with the progression to active TB within 2 years. Forty‐one HIV‐infected antiretroviral‐naïve subjects were prospectively enrolled: 18 were HIV‐TB and 23 HIV‐LTBI. Whole blood was in vitro stimulated overnight with several antigens and mitogen. Interferon‐γ response in the harvested plasma was evaluated by ELISA. Despite that CD4 cell count was significantly different between HIV‐LTBI and HIV‐TB, no differences were observed in response to Mtb‐ or HIV‐specific antigens. Differently, low responses to HBHA were observed in both HIV‐LTBI and HIV‐TB subjects. Importantly, none of the six HIV‐LTBI responding to HBHA developed TB, while two of 17 non‐HBHA responders developed active disease. HIV‐TB‐coinfected subjects, regardless of their TB status, showed low responses to HBHA despite maintaining detectable responses to other antigens; moreover, among the HIV‐LTBI, the lack of HBHA responses indicated an increased risk to develop active TB. These results, although preliminary, suggest that a positive response to HBHA in HIV‐LTBI correlates with Mtb containment.
Integrase drug resistance monitoring deserves attention because of the increasing number of patients being treated with integrase strand-transfer inhibitors. Therefore, we evaluated the integrase ...genotyping success rate at low-level viraemia (LLV, 51-1000 copies/mL) and resistance in raltegravir-failing patients.
An integrase genotypic resistance test (GRT) was performed on 1734 HIV-1 samples collected during 2006-13. Genotyping success rate was determined according to the following viraemia levels: 51-500, 501-1000, 1001-10 000, 10 001-100 000 and >100 000 copies/mL. The reproducibility of integrase GRT was evaluated in 41 plasma samples processed in duplicate in two reference centres. The relationship between LLV and resistance prevalence was evaluated in a subset of 120 raltegravir-failing patients.
Overall, the integrase genotyping success rate was 95.7%. For viraemia levels 51-500 and 501-1000 copies/mL, the rate of success was 82.1% and 94.0%, respectively. GRT was reproducible, producing sequences with a high similarity and an equal resistance profile regardless of the sequencing centre or viraemia level. Resistance was detected both at LLV and at viraemia >1000 copies/mL (51-500 copies/mL = 18.2%; 501-1000 = 37.5%; 1001-10 000 = 53.7%; 10 001-100 000 = 30.0%; and >100 000 = 30.8%). At viraemia ≤500 copies/mL, Q148H/K/R and N155H had the same prevalence (9.1%), while the Y143C/H/R was completely absent. At early genotyping (within 3 months of raltegravir treatment), Q148H/K/R and N155H mutations were detected regardless of the viraemia level, while Y143C/H/R was observed only in samples with viraemia >1000 copies/mL.
Our findings prove the reliability of HIV-1 integrase genotyping and reinforce the concept that this assay may be useful in the management of failures even at LLV.
Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice‐daily recipients. We studied abacavir CSF ...concentrations in 61 and nine HIV‐positive patients taking abacavir once daily and twice daily, respectively. Patients on once‐daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml−1, P = 0.038 and 123 vs. 49 ng ml−1, P = 0.038) but similar CSF‐to‐plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once‐daily treatment.
Objectives
The aim of this study was to evaluate the factors that can influence an incomplete viral response (IVR) after acute and early HIV infection (AEHI).
Methods
This was a retrospective, ...observational study including patients with AEHI (Fiebig stages I–V) diagnosed between January 2008 and December 2014 at 20 Italian centres. IVR was defined by: (1) viral blip (51–1000 HIV‐1 RNA copies/mL after achievement of < 50 HIV‐1 RNA copies/mL); (2) virologic failure > 1000 copies/mL after achievement of < 200 copies/mL, or ≥ 200 copies/mL after 24 weeks on an antiretroviral therapy (ART); (3) suboptimal viral response (> 50 copies/mL after 48 weeks on ART or two consecutive HIV‐1 RNA levels with ascending trend during ART). Cox regression analysis was used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for IVR.
Results
In all, 263 patients were studied, 227 (86%) males, with a median interquartile range (IQR) age of 38 (30–46) years. During a median follow‐up of 13.0 (5.7–31.1) months, 38 (14.4%) had IVR. The presence of central nervous system (CNS) symptoms was linked to a higher risk of IVR (HR = 4.70, 95% CI: 1.56–14.17), while a higher CD4/CD8 cell count ratio (HR = 0.13, 95% CI: 0.03–0.51 for each point increase) and first‐line ART with three‐drug regimens recommended by current guidelines (HR = 0.40, 95% CI: 0.18–0.91 compared with other regimens including four or five drugs, older drugs or non‐standard backbones) were protective against IVR.
Conclusions
Patients with lower CD4/CD8 ratio and CNS symptoms could be at a higher risk of IVR after AEHI. The use of recommended ART may be relevant for improving short‐term viral efficacy in this group of patients.
Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in ...pregnancy using data from a national observational study.
Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score).
Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P < 0.001).
In this observational study, the two main HIV PIs currently recommended by perinatal guidelines showed similar safety and activity in pregnancy, with no evidence of differences between the two drugs in terms of main pregnancy outcomes. Based on the minor differences observed in laboratory measures, prescribing physicians might prefer either drug in some particular situations where the different impacts of treatment on lipid profile and bilirubin may have clinical relevance.
A tuberculosis (TB) referral centre in Rome, Italy.
To identify demographic and epidemiological characteristics associated with diabetes mellitus (DM) among patients with TB and to compare the ...clinical presentation of TB and TB-DM in the light of the growing worldwide burden of DM.
We performed a retrospective study of TB cases diagnosed from 2007 to 2012.
Among 971 TB patients, 723 were foreign-born and 63 (6.5%) had DM. DM prevalence was 12.7% (8/63) among those born in countries with DM prevalence ⩾8%, 4.7% (31/660) among patients from countries with DM prevalence <8% and 9.7% among Italian patients (24/248). In multivariable analysis, DM was independently associated with older age, and with being born in countries other than Italy, compared to Italians; this latter association was stronger in older patients. DM patients were also significantly more likely to be male and less likely to test positive for the human immunodeficiency virus. The presence of cavities was significantly associated with DM.
As individuals born in high TB incidence and high DM prevalence countries emerge as a vulnerable population, greater attention to bidirectional low-cost screening in people from these countries is needed.
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.
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