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• 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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care.Methods: In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters.Results: Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (<2005-14: 19.5%-38.5%, P < 0.0001), particularly among Italians (<2005-14: 6.5%-28.8%, P < 0.0001). TDR prevalence was 8.8% and increased over time in non-B subtypes (<2005-14: 2%-7.1%, P = 0.018). Overall, 467 transmission clusters (involving 1207 individuals; 27.9%) were identified. The prevalence of individuals grouping in transmission clusters increased over time in both B (<2005-14: 12.9%-33.5%, P = 0.001) and non-B subtypes (<2005-14: 18.4%-41.9%, P = 0.006). TDR transmission clusters were 13.3% within the overall cluster observed and dramatically increased in recent years (<2005-14: 14.3%-35.5%, P = 0.005). This recent increase was mainly due to non-B subtype-infected individuals, who were also more frequently involved in large transmission clusters than those infected with a B subtype [median number of individuals in transmission clusters: 7 (IQR 6-19) versus 4 (3-4), P = 0.047].Conclusions: The epidemiology of HIV transmission changed greatly over time; the increasing number of transmission clusters (sometimes with drug resistance) shows that detection and proper treatment of the multi-transmitters is a major target for controlling HIV spread. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio ( OR) 1.36; 95% confidence interval ( CI) 1.10-1.68], diagnosed with HIV infection in the current pregnancy ( OR: 1.69; 95% CI: 1.35-2.11), and at their first pregnancy ( OR: 1.33; 95% CI: 1.06-1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C ( CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: 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. Methods: 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, 1001-10000, 10001-100000 and .100000 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. Results: 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%; 1001-10000=53.7%; 10001-100000=30.0%; and .100000=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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objective We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design Observational study. Setting University and hospital clinics. Population Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios ( ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9-4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9-4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment ( OR 0.94, 95% CI 0.51-1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51-1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56-2.55; protease inhibitors, OR 0.92, 95% CI 0.43-1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities. [ABSTRACT FROM AUTHOR]

Nonadherence to antiretroviral therapy (ART) may cause virologic failure and disease progression has been associated with switch of viral coreceptor usage from CCR5 to CXCR4. We aimed to assess the association between patient-reported non-adherence and HIV tropism. This is a cross-sectional analysis. HIV-tropism was performed within routine clinical practice either at start of ART or at virological failure. Adherence questionnaire includes: how many times ART has been taken during the last month, missed doses in the last week, timing deviation, refill interruption, drug holidays. Demographics, epidemiological data, HIV and ART history, CD4 and HIVRNA were collected. To assess co-receptor tropism, env V3 genotyping from viremic plasma HIVRNA was performed. For the analysis, dual/mixed viruses were considered as X4. We included 102 individuals: 76% males; median age 42 y (IQR, 37-46); transmission was heterosexual 37%, homosexual 31%, intravenous drug use 29%. Median nadir of CD4 154/mmc (IQR, 53-274), median zenith of HIVRNA 5.26 (4.72-5.70), 46% had AIDS. 124 tropism tests were: 78% R5, 17% X4, 5% dual/mixed. In cases with previous ART, mono/dual ART was found in 26%, median number of regimens was 5 (IQR, 2-10), median time on triple-ART was 54 months (IQR, 0-123) with median time of HIVRNA <50 c/ml of 16 months (IQR, 6.5-34.9). At HIV-tropism, median CD4 and HIV RNA were 321/mmc (IQR, 210-436) and 2.65 (IQR, 2.65-4.91), respectively. Median time between adherence questionnaire and HIV-tropism was 68 days (IQR, 23-116). At adherence questionnaire, median percentage of ART taken during the last month was 100% (IQR, 90-100), 39% reported missed doses in the last week, 40% timing deviation, 7% refill interruption, 17% drug holidays. At univariate analysis, no statistically significant association between non-adherence and dual/mixed-X4 viruses was found (p>0.1). Also gender, age, HIV transmission, AIDS, CD4 nadir, HIVRNA zenith, mono/dual ART, and number of ART regimens were not associated with type of tropism. Only longer time with undetectable HIVRNA before tropism test showed a lower probability of dual/mixed-X4 viruses (OR for each month 0.95; 95% CI 0.90-1.00; p=0.06). No significant association between adherence and HIV-tropism was found in this preliminary analysis. It is possible that patient self-reported adherence is not able to capture nonadherence behaviors that underlie more pronounced viral replication which may be necessary for tropism switch. [ABSTRACT FROM AUTHOR]

An abstract of the article "No significant association between patient self-reported nonadherence to antiretrovirals and HIV-tropism: a preliminary analysis," by P. Pierro and colleagues is presented.

7-11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK [ABSTRACT FROM AUTHOR]

An abstract to an article on HIV-infected patients with Hodgkin lymphoma is presented.

The article focuses on a study regarding the impact of cytomegalovirus (CMV) coinfection on pregnant women with HIV. It mentions the link of maternal immunosuppression with higher risk of CMV infant infection and states the CMV DNAaemia to higher maternal and infant mortality. It also mentions that the pregnant women with HIV has positive serology for CMV.

We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001–06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women. [ABSTRACT FROM AUTHOR]