HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch.

Hepatitis B Core antibody (HBcAb) positivity is the surrogate marker of hepatitis B occult infection. This condition is not a contraindication for switching to two-drug (2DR) antiretroviral therapy; however, the removal of tenofovir may contribute to poor control of HBV replication. A multicentre retrospective cohort study investigated the impact of HBcAb positivity on HIV control in patients switching to a 2DR with Lamivudine and Dolutegravir (3TC-DTG). In this study, a comparison analysis was conducted between HBcAb-positive and -negative PLWH regarding HIV-RNA suppression, considering: (1): Target Not Detected (TND) < 20 cp/mL; (2) Target Detected (TD) < 20 cp/mL; and (3) Detectable > 20 cp/mL and <50 cp/mL and >50 copies/mL. A total of 267 patients on 2DR with 3TC-DTG were included. In comparison to HBcAb-negative, HBcAb-positive patients were older (45 years [35-54]) and had a lower CD4+ nadir (248 vs. 349 cells/mmc, p = 0.007). No difference in the maintenance of virological suppression was present in the two groups of patients before the switch. Although no patient had an HIV-RNA > 20 cp/mL after the switch, significantly fewer HBcAb-positive compared with -negative subjects resulted in TND at 12, 24, and 36 months after the switch: 52 (69.3%) versus 164 (85.4%), p = 0.004, 50 [72.5%] versus 143 [89.9%], p = 0.001, and 30 [66.7%] versus 90 [92.8%], p = 0.001, respectively. HBcAb positivity is associated with an increased risk of suboptimal HIV suppression during the 36 months after 3TC/DTG simplification. This finding reinforces the relevance of the OBI condition in PLWH and raises the issue of careful virological monitoring of such cases.

Predicting Factors of Plasma HIV RNA Undetectability after Switching to Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Experienced HIV-1 Patients: A Multicenter Study.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019-2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan-Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

SARS-CoV-2 Neutralizing Antibodies to B.1 and to BA.5 Variant after Booster Dose of BNT162b2 Vaccine in HIV Patients COVID-Naïve and on Successful Antiretroviral Therapy.

Live virus neutralization is the gold standard to investigate immunity. This prospective observational study aimed to determine the magnitude of response against the original B.1 lineage and against the BA.5 lineage six months after the third BNT162b2 mRNA vaccine dose in patients with HIV infection on successful antiretroviral treatment and no previous SARS-CoV-2 infection. A total of 100 subjects (M/F 83/17, median age 54 years) were included in the analysis: 95 had plasma HIV RNA <40 copies/mL, the median CD4+ T cell count at the administration of the third dose was 580 cells/mm3, and the median nadir CD4+ T cell count was 258 cells/mm3. Neutralizing antibodies (NtAb) against B.1 were detectable in all the subjects, but those to BA.5 were only detected in 88 (p < 0.001). The median NtAb titer to B.1 was significantly higher than that to BA.5 (393 vs. 60, p < 0.0001), and there was a strong positive correlation between the paired measurements (p < 0.0001). Linear regression on a subset of 87 patients excluding outlier NtAb titers showed that 48% of the changes in NtAb titers to BA.5 are related to the changes in value titers to B.1. SARS-CoV-2 variants evolve rapidly, challenging the efficacy of vaccines, and data on comparative NtAb responses may help in tailoring intervals between vaccine doses and in predicting vaccine efficacy.

Role of HBcAb Positivity in Increase of HIV-RNA Detectability after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Months 48 Results of a Multicenter Italian Cohort.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of HIV viremia in patients living with HIV (PLWH) who switch to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC-based). A retrospective multicentre observational study was conducted on 160 PLWH switching to the 2DR-3TC-based regimen: 51 HBcAb-positive and 109 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly lower percentage of subjects with HIV viral suppression with target not detected (TND) at all time points after switching (24th month: 64.7% vs. 87.8%, p < 0.0001; 36th month 62.7% vs. 86.8%, p = 0.011; 48th month 57.2% vs. 86.1%, p = 0.021 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that the presence of HBcAb positivity (OR 7.46 [95% CI 2.35−14.77], p = 0.004) could favour the emergence of HIV viral rebound by nearly 54% during the entire study follow-up after switching to 2DR-3TC.

Long-Term Longitudinal Analysis of Neutralizing Antibody Response to Three Vaccine Doses in a Real-Life Setting of Previously SARS-CoV-2 Infected Healthcare Workers: A Model for Predicting Response to Further Vaccine Doses.

We report the time course of neutralizing antibody (NtAb) response, as measured by authentic virus neutralization, in healthcare workers (HCWs) with a mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection diagnosed at the onset of the pandemic, with no reinfection throughout and after a three-dose schedule of the BNT162b2 mRNA vaccine with an overall follow-up of almost two years since infection. Forty-eight HCWs (median age 47 years, all immunocompetent) were evaluated: 29 (60.4%) were asymptomatic. NtAb serum was titrated at eight subsequent time points: T1 and T2 were after natural infection, T3 on the day of the first vaccine dose, T4 on the day of the second dose, T5, T6, and T7 were between the second and third dose, and T8 followed the third dose by a median of 34 days. NtAb titers at all postvaccination time points (T4 to T8) were significantly higher than all those at prevaccination time points (T1 to T3). The highest NtAb increase was following the first vaccine dose while subsequent doses did not further boost NtAb titers. However, the third vaccine dose appeared to revive waning immunity. NtAb levels were positively correlated at most time points suggesting an important role for immunogenetics.

Comparable Post-Vaccination Decay of Neutralizing Antibody Response to Wild-Type and Delta SARS-CoV-2 Variant in Healthcare Workers Recovered from Mild or Asymptomatic Infection.

We described the long-term decay of neutralizing antibody (NtAb) to the wild-type and Delta SARS-CoV-2 variant after three antigen stimulations (mild or asymptomatic natural infection followed by two doses of the BNT162b2 mRNA vaccine after a median of 296 days) in immunocompetent healthcare workers (HCWs). Live virus microneutralization against the B.1 and Delta SARS-CoV-2 variants was performed in VERO E6 cell cultures. The median NtAb titers for B.1 and Delta were comparable and highly correlated at both 20 and 200 days after the second vaccine dose in the 23 HCWs enrolled (median age, 46 years). A small group of naturally infected unvaccinated HCWs had comparable NtAb titers for the two strains after a median follow-up of 522 days from infection diagnosis. The NtAb response to the Delta VoC appears to follow the same long-term dynamics as the wild-type response regardless of the vaccinal boost; data collected after three antigen stimulations (natural infection followed by two doses of the BNT162b2 mRNA vaccine) may be helpful for tailoring the continuous monitoring of vaccine protection against SARS-CoV-2 variants over time.

Humoral Response after Two Doses of BNT162b2 mRNA Vaccine Has a Role in Predicting Response after Three Doses That Is Related to Plasma HIV Viremia and Nadir CD4+ Cell Count in HIV-Positive Patients.

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th−25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects.

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BLinf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2uninf). All the subjects received BNT162b2 vaccination. D1inf NtAbT increased significantly with respect to BLinf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1inf NtAbT were significantly higher than D2uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination.

Faster decay of neutralizing antibodies in never infected than previously infected healthcare workers three months after the second BNT162b2 mRNA COVID-19 vaccine dose.

OBJECTIVES: This study aimed to describe the longitudinal evolution of neutralizing antibody titres (NtAb) in three different cohorts of healthcare workers (HCWs), including vaccinated HCWs with and without a previous SARS-CoV-2 infection and previously infected unvaccinated HCWs. COVID-19 was mild or asymptomatic in those experiencing infection. METHODS: NtAb was tested before BNT162b2 mRNA COVID-19 vaccine (V0), 20±2 days after the first dose (V1_20), 20±3 days (V2_20) and 90±2 days (V2_90) after the second dose in vaccinated HCWs and after about 2 months (N_60), 10 months (N_300) and 13 months (N_390) from natural infection in unvaccinated HCWs. NtAb were measured by authentic virus neutralization with a SARS-CoV-2 B.1 isolate circulating in Italy at HCW enrolment. RESULTS: Sixty-two HCWs were enrolled. NtAb were comparable in infected HCWs with no or mild disease at all the study points. NtAb of uninfected HCWs were significantly lower with respect to those of previously infected HCWs at V1_20, V2_20 and V2_90. The median NtAb fold decrease from V2_20 to V2_90 was higher in the uninfected HCWs with respect to those with mild infection (6.26 vs 2.58, p=0.03) and to asymptomatic HCWs (6.26 vs 3.67, p=0.022). The median Nabt at N_390 was significantly lower than at N_60 (p=0.007). CONCLUSIONS: In uninfected HCWs completing the two-dose vaccine schedule, a third mRNA vaccine dose is a reasonable option to counteract the substantial NtAb decline occurring at a significantly higher rate compared with previously infected, vaccinated HCWs. Although low, Nabt were still at a detectable level after 13 months in two-thirds of previously infected and unvaccinated HCWs.

Time Course of Neutralizing Antibody in Health Care Workers With Mild or Asymptomatic COVID-19 Infection.

We describe the time course of neutralizing antibody (NtAb) titer in a cohort of health care workers with mild or asymptomatic severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. NtAb levels decreased over time; however, serum neutralizing activity remained detectable after a median of 7 months from SARS-CoV-2 diagnosis in the majority of cases.

Single-dose BNT162b2 mRNA COVID-19 vaccine significantly boosts neutralizing antibody response in health care workers recovering from asymptomatic or mild natural SARS-CoV-2 infection.

OBJECTIVES: To measure SARS-CoV-2 neutralizing antibody (NtAb) titres in previously infected or uninfected health care workers who received one or two doses of BNT162b2 mRNA COVID-19 vaccine. METHODS: NtAbs were titrated as dose-inhibiting 50% virus replication (ID50) by live virus microneutralization. We evaluated 41 health care workers recovering from mild or asymptomatic infection at first vaccination dose (T1_inf) and 21 days later (T2_inf). Sixteen uninfected health care workers were evaluated 20 days after first dose (T2_uninf) and 20 days after second vaccine dose (T3_uninf). RESULTS: At T2_inf, but not at T1_inf, there was a significant correlation between days from diagnosis (median 313, interquartile range 285-322) and NtAb levels (P = 0.011). NtAb titres increased at T2_inf with respect to T1_inf (1544 (732-2232) vs 26 (10-88), P < 0.001). Similarly, there was a significant increase in NtAb titres at T3_uninf compared with T2_uninf (183 (111-301) vs 5 (5-15), P < 0001). However, NtAb levels at T2_inf were significantly higher than those at T2_uninf and T3_uninf (P < 0.0001 for both analyses). CONCLUSIONS: A single vaccination in people with mild or asymptomatic previous infection further boosts SARS-CoV-2 humoral immunity to levels higher than those obtained by complete two-vaccination in uninfected subjects.

HIV tropism switch in archived DNA of HIV-HCV subjects successfully treated with direct-acting antivirals for HCV infection.

We described short-term HIV tropism changes occurring in peripheral blood mononuclear cells and the correlations with HIV DNA value in HIV-HCV co-infected patients cured for HCV disease and with undetectable HIV viremia or residual viremia (RV). Plasma HIV RNA, cellular HIV DNA and tropism were evaluated pre-HCV treatment (baseline, BL) and at 12(T1) and 24(T2) weeks after HCV treatment start. V3 sequences were interpreted using Geno2pheno and classified as R5 only if all three sequences had an FPR ≥ 10% and as X4 when at least one replicate sequence had an FPR < 10%. Forty-nine patients (21 with X4 and 28 with R5 virus) were enrolled. Five X4 patients and 9 R5 subjects experienced at least one tropism change,11 with RV:1/5 patients with X4 infection at BL switched at T1 versus 8/9 in the R5 group (p = 0.022977) and the difference was confirmed in subjects with RV (p = 0.02);6/9 R5 patients switching at T1 confirmed the tropism change at T2. No significant differences in HIV DNA values between patients with RV starting with a R5 or X4 tropism and experienced tropism switch or not were found. Short-term tropism switch involved almost a third of patients, in all but three cases with HIV RV. Being R5 at BL is associated to a higher instability, expressed as number of tropism changes and confirmed switch at T2.

HBcAb Positivity Is a Risk Factor for an Increased Detectability of HIV RNA after Switching to a Two-Drug Regimen Lamivudine-Based (2DR-3TC-Based) Treatment: Analysis of a Multicenter Italian Cohort.

The aim of this study was to evaluate whether the presence of anti-hepatitis B (HBV) c antibodies (HBcAb positivity) could influence the control of Human Immunodeficiency Virus (HIV) viremia in patients living with HIV (PLWH) who switch a to two-drug antiretroviral therapy (2DR) containing lamivudine (3TC) (2DR-3TC). A retrospective observational multicenter study was conducted on 166 PLWH switching to the 2DR-3TC-based regimen: 58 HBcAb-positive and 108 HBcAb-negative patients. The HBcAb-positive PLWH group demonstrated a significantly higher percentage of subjects with very low-level viremia at all time points after switching (6th month: <31% vs. 17.6%, p = 0.047; 12th month 34% vs. 27.5%, p = 0.001; 24th month 37% vs. 34.2, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively) and a higher percentage of subjects with detectable HIV RNA greater than 20 copies/mL 12 and 24 months after switching (12 months 32% vs. 11%, p = 0.001; 24 months 37% vs. 13.9%, p = 0.003 of the HBcAb-positive and HBcAb-negative groups, respectively). Logistic regression analysis showed that an increase in age of ten years (OR 2.48 (95% CI 1.58-3.89), p < 0.0001) and the presence of HBcAb positivity (OR 2.7 (5% CI 1.05-6.9), p = 0.038) increased the risk of detectability of HIV RNA by nearly three-fold after switching to 2DR-3TC.

Intra-hospital acquisition of colonization and infection by Klebsiella pneumoniae strains producing carbapenemases and carriage evolution: A longitudinal analysis in an Italian teaching hospital from January 2017 to August 2019.

OBJECTIVES: We present an updated picture (1/1/2017-31/08/2019) of the frequency of carbapenemase producing Klebsiella pneumoniae (CPKP) in surveillance rectal swabs (SRS) and in clinical samples (CS) of patients admitted to a tertiary level hospital, focusing on longitudinal evolution of CPKP detected in SRS and on colistin resistant strains. METHODS: Retrospective longitudinal analysis. Only the first positive CPKP strain isolated from each patient was included. RESULTS: 638 CPKP strains were identified (471 in SRS and 167 in CS). SRS frequency increased over time in the medical department, remained high in the surgical department (SD) and decreased in the intensive care department. Most SRS-71.3%-and 49.1% of CS had nosocomial origin; about half of the SRS were identified in the SD. Regarding SRS evolution, carriage was confirmed in 39.5% of patients, no more testing in 25.5%, clinical involvement in 24.8 %, and negative result in 10.2%. Rates of colistin resistance were 20.1% in 2017, 31.2% in 2018 and 26.9% in 2019. CONCLUSIONS: CPKP diffusion is still an important issue despite the surveillance program. It is vital to enhance medical staff's awareness on this because most CPKP first detections in SRS occurred during hospital stay due to a nosocomial acquisition with a comparable picture over time. Colistin resistance is increasing.

A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit.

The Ralstonia spp. genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns.

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications.

BACKGROUND: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). METHODS: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. RESULTS: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. CONCLUSIONS: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Role of pretreatment variables on plasma HIV RNA value at the sixth month of antiretroviral therapy including all first line drugs in HIV naïve patients: A path analysis approach.

BACKGROUND AND AIMS: We investigated the conditioning roles of viral tropism and other variables on plasma HIV RNA levels after 6 months of combination antiretroviral therapy (cART) in an HIV-infected Italian naïve population using regression tree, random forest regression, and path analysis (PA). Patients in this multicenter observational study were treated with all antiviral drugs that are currently recommended as first-line therapies. METHODS: Adult patients with chronic HIV infection were enrolled at the beginning of first-line cART (T0). The main variables were age, gender, tropism, "lcd4_0" and "lcd4_6" (log10 CD4+counts at T0 and after 6 months of cART, respectively), and "lrna0" (log10 HIV RNA at T0). Regression tree and random forest analyses were applied. The predictive effect on lrna6 (log10-transformed plasma HIV RNA after 6 months of cART) was also investigated via PA (x4->lcd4_0->lrna0->lrna6) with a treatment selection step included as a dependent (mediator) variable for each third drug and, as predictive covariates, age, female, x4_10, x4_5, lcd4_0, and lrna0. Tropism was assessed in plasma using the Geno2pheno algorithm with 2 false positive rate (FPR) cut-offs: 5% (x4_5) and 10% (x4_10). RESULTS: The study included 571 subjects (21% x4_10 and 10.7% x4_5). The only important predictor of lrna6 was lrna0, and a positive indirect effect of bearing X4 virus in plasma was suggested. A significant direct positive effect of protease inhibitors on lrna6 was found (p = 0.022), and a significant negative effect of integrase strand transfer inhibitor (INSTI) was also detected (p = 0.003 for FPR ≤ 5% and p = 0.01 for FPR < 10%). PA predicted mean residual viremias of 40 copies/mL without INSTI and 3 copies/mL with INSTI. CONCLUSIONS: PA indicated a possible indirect role of HIV tropism on lrna6 with both FPR < 10% and ≤ 5%. Patients treated with INSTI had a predicted residual viremia of 3 copies/mL.