Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV.

BACKGROUND: The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown. METHODS: 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform. RESULTS: 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7. CONCLUSION: Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

T-Cell Immunity Against Severe Acute Respiratory Syndrome Coronavirus 2 Measured by an Interferon-γ Release Assay Is Strongly Associated With Patient Outcomes in Vaccinated Persons Hospitalized With Delta or Omicron Variants.

BACKGROUND: We measured T-cell and antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaccinated patients hospitalized for coronavirus disease 2019 (COVID-19) and explored their potential value to predict outcomes. METHODS: This was a prospective, longitudinal study including vaccinated patients hospitalized with Delta and Omicron SARS-CoV-2 variants. TrimericS-IgG antibodies and SARS-CoV-2 T-cell response were measured using a specific quantitative interferon-γ release assay (IGRA). Primary outcome was all-cause 28-day mortality or need for intensive care unit (ICU) admission. Cox models were used to assess associations with outcomes. RESULTS: Of 181 individuals, 158 (87.3%) had detectable SARS-CoV-2 antibodies, 92 (50.8%) showed SARS-CoV-2-specific T-cell responses, and 87 (48.1%) had both responses. Patients who died within 28 days or were admitted to ICU were less likely to have both unspecific and specific T-cell responses in IGRA. In adjusted analyses (adjusted hazard ratio [95% confidence interval]), for the entire cohort, having both T-cell and antibody responses at admission (0.16 [.05-.58]) and Omicron variant (0.38 [.17-.87]) reduced the hazard of 28-day mortality or ICU admission, whereas higher Charlson comorbidity index score (1.27 [1.07-1.51]) and lower oxygen saturation to fraction of inspired oxygen ratio (2.36 [1.51-3.67]) increased the risk. CONCLUSIONS: Preexisting immunity against SARS-CoV-2 is strongly associated with patient outcomes in vaccinated individuals requiring hospital admission for COVID-19. Persons showing both T-cell and antibody responses have the lowest risk of severe outcomes.

Human Immunodeficiency Virus Type 1 RNA Levels in Rectal and Seminal Compartments After Switching to Long-Acting Cabotegravir Plus Rilpivirine: A Longitudinal Study.

Human immunodeficiency virus type 1 RNA levels were longitudinally evaluated in 211 rectal and 152 seminal samples from 12 virologically suppressed participants switching to monthly long-acting cabotegravir plus rilpivirine or continuing with daily dolutegravir-abacavir-lamivudine. Maintenance of viral suppression in rectal and seminal compartments was comparable, and blips occurred with similar frequency with both treatment regimens. CLINICAL TRIALS REGISTRATION: NCT02938520.

Immunologic phenotype of patients with long-COVID syndrome of 1-year duration.

Background: The pathophysiology of long-COVID remains unknown, and information is particularly limited for symptoms of very long duration. We aimed to assess the serological, T-cell immune responses and ANA titers of patients with long-COVID-19 syndrome of 1-year duration. Methods: Prospective, longitudinal study of hospitalized COVID-19 patients followed-up for 12 months. Sequential blood samples and COVID-19 symptom questionnaires (CSQ) were obtained, and humoral and cellular immune responses, antinuclear antibodies (ANA) and inflammation biomarkers were analyzed. Results: Of 154 patients discharged from hospital, 72 non-vaccinated with available CSQ in all visits were included. Of them, 14 (19.4%) reported persistent symptoms both at 6-months and 12-months, mainly asthenia (15.3%), myalgia (13.9%), and difficulty concentrating/memory loss (13.9%). Symptomatic patients were more frequently women, smokers, showed higher WHO severity score, and a trend to higher ICU admission. In the adjusted analysis, long-COVID syndrome was associated with lower frequency of detectable neutralizing antibodies (adjusted hazard ratio [aHR] 0.98; 95% confidence interval [CI], 0.97-0.99) and lower SARS-CoV-2-S1/S2 titers (aHR [95%CI] 0.14 [0.03-0.65]). T-cell immune response measured with a SARS-CoV-2-interferon-γ release assay was not different between groups. There was a higher frequency of positive ANA titers (≥160) in symptomatic patients (57.1% vs 29.3%, p=0.04), that was attenuated after adjustment aHR [95% CI] 3.37 [0.84-13.57], p=0.087. Levels of C-reactive protein and D-dimer were higher during follow-up in symptomatic patients, but with no differences at 12 months. Conclusion: Patients with 1-year duration long-COVID-19 syndrome exhibit a distinct immunologic phenotype that includes a poorer SARS-CoV-2 antibody response, low-degree chronic inflammation that tends to mitigate, and autoimmunity.

Robust long-term immunity to SARS-CoV-2 in patients recovered from severe COVID-19 after interleukin-6 blockade.

BACKGROUND: Whether interleukin-6 (IL-6) blockade in patients with COVID-19 will affect the protective immunity against SARS-CoV-2 has become an important concern for anti-IL-6 therapy. We aimed to investigate the effects of IL-6 blockade on long-term immunity to SARS-CoV-2. METHODS: Prospective, longitudinal cohort study conducted in patients hospitalized for severe or critical COVID-19 with laboratory confirmed SARS-CoV-2 infection. We assessed humoral (anti-S1 domain of the spike [S], anti-nucleocapsid [N], anti-trimeric spike [TrimericS] IgG, and neutralizing antibodies [Nab]) and T-cell (interferon-γ release assay [IGRA]) responses and evaluated the incidence of reinfections over one year after infection in patients undergoing IL-6 blockade with tocilizumab and compared them with untreated subjects. FINDINGS: From 150 adults admitted with confirmed SARS-CoV-2 infection, 78 were 1:1 propensity score-matched. Patients receiving anti-IL6 therapy showed a shorter time to S-IgG seropositivity and stronger S-IgG and N-IgG antibody responses. Among unvaccinated subjects one year after infection, median (Q1-Q3) levels of TrimericS-IgG (295 vs 121 BAU/mL; p = 0.011) and Nab (74.7 vs 41.0 %IH; p = 0.012) were higher in those undergoing anti-IL6 therapy, and a greater proportion of them had Nab (80.6% vs 57.7%; p = 0.028). T-cell immunity was also better in those treated with anti-IL6, with higher median (Q1-Q3) interferon-γ responses (1760 [702-3992] vs 542 [35-1716] mIU/mL; p = 0.013) and more patients showing positive T-cell responses in the IGRA one year after infection. Patients treated with anti-IL6 had fewer reinfections during follow-up and responded to vaccination with robust increase in both antibody and T-cell immunity. INTERPRETATION: IL-6 blockade in patients with severe COVID-19 does not have deleterious effects on long-term immunity to SARS-CoV-2. The magnitude of both antibody and T-cell responses was stronger than the observed in non-anti-cytokine-treated patients with no increase in the risk of reinfections. FUNDING: Instituto de Salud Carlos-III (Spain).

Clinical Performance of a Standardized Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Interferon-γ Release Assay for Simple Detection of T-Cell Responses After Infection or Vaccination.

BACKGROUND: We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. METHODS: This prospective study included patients with coronavirus disease 2019 (COVID-19) with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of reverse transcription-polymerase chain reaction or vaccination was considered as the reference standard. RESULTS: A total of 239 individuals were included (152 convalescent, 54 vaccinated, and 33 uninfected unvaccinated). Overall sensitivity, specificity, and positive- and negative-predictive values (95% confidence interval) of the IGRA were 81.1% (74.9-86%), 90.9% (74.5-97.6%), 98.2% (94.5-99.5%), and 43.5% (31.8-55.9%), respectively. All vaccinated SARS-CoV-2-naive subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3 months and the worst in those with mild disease at 12 months. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). CONCLUSIONS: The IGRA was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients, the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.

Antibody Response to SARS-CoV-2 is Associated with Long-term Clinical Outcome in Patients with COVID-19: a Longitudinal Study.

BACKGROUND: The relationship of host immune response and viral replication with health outcomes in patients with COVID-19 remains to be defined. We aimed to characterize the medium and long-term clinical, virological, and serological outcomes after hospitalization for COVID-19, and to identify predictors of long-COVID. METHODS: Prospective, longitudinal study conducted in COVID-19 patients confirmed by RT-PCR. Serial blood and nasopharyngeal samples (NPS) were obtained for measuring SARS-CoV-2 RNA and S-IgG/N-IgG antibodies during hospital stay, and at 1, 2, and 6 months post-discharge. Genome sequencing was performed where appropriate. Patients filled out a COVID-19 symptom questionnaire (CSQ) at 2-month and 6-month visits, and those with highest scores were characterized. RESULTS: Of 146 patients (60% male, median age 64 years) followed-up, 20.6% required hospital readmission and 5.5% died. At 2 months and 6 months, 9.6% and 7.8% patients, respectively, reported moderate/severe persistent symptoms. SARS-CoV-2 RT-PCR was positive in NPS in 11.8% (median Ct = 38) and 3% (median Ct = 36) patients at 2 months and 6 months, respectively, but no reinfections were demonstrated. Antibody titers gradually waned, with seroreversion occurring at 6 months in 27 (27.6%) patients for N-IgG and in 6 (6%) for S-IgG. Adjusted 2-month predictors of the highest CSQ scores (OR [95%CI]) were lower peak S-IgG (0.80 [0.66-0.94]) and higher WHO severity score (2.57 [1.20-5.86]); 6-month predictors were lower peak S-IgG (0.89 [0.79-0.99]) and female sex (2.41 [1.20-4.82]); no association was found with prolonged viral RNA shedding. CONCLUSIONS: Long-COVID is associated with weak anti-SARS-CoV-2 antibody response, severity of illness, and female gender. Late clinical events and persistent symptoms in the medium and long term occur in a significant proportion of patients hospitalized for COVID-19.

Durable antibody response one year after hospitalization for COVID-19: A longitudinal cohort study.

OBJECTIVES: Durability of the humoral immune response to SARS-CoV-2 has yet to be defined. We longitudinally evaluated during a 12-month period the antibody responses to SARS-CoV-2, and analysed predictors of antibody titres decline and seroreversion. METHODS: Prospective study conducted in a cohort of patients hospitalized for microbiologically-confirmed COVID-19. Blood and nasopharyngeal samples were sequentially obtained during hospital stay and at 1, 2, 6 and 12 months after patients' discharge for measuring anti-spike (S) and anti-nucleocapsid (N) IgG antibody levels and SARS-CoV-2 RNA, respectively. RESULTS: 80 non-vaccinated patients were analysed. At month 12 after discharge, 73 (91.2%) patients exhibited detectable S-IgG and 35 (43.8%) N-IgG antibody titres. A gradual wane was observed in S-IgG and N-IgG antibody titres. Linear regression showed that S-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.059 [0.05-0.067], p < 0.001), inversely with WHO severity score (coefficient [95% CI] -0.042 [-0.079/-0.004], p = 0.033), and there was a trivial positive association with age (coefficient [95% CI] 0.002 [0-0.005], p = 0.10); N-IgG decline was positively associated with peak antibody titres (coefficient [95% CI] 0.091 [0.078-0.105], p < 0.001). Logistic regression showed that seroreversion for S-IgG was inversely associated with peak S-IgG (OR 0.19; 95% CI, 0.04-0.45; p = 0.004); seroreversion for N-IgG was inversely associated with peak N-IgG (OR 0.71; 95% 0.53-0.90; p = 0.009) and positively with cycle threshold of RT-PCR (OR 1.14; 95% CI, 1.00-1.33; p = 0.062). CONCLUSION: Anti-spike IgG antibodies remain detectable one year after hospitalization for COVID-19. Higher peak antibody titres and disease severity were associated with increased durability of detectable antibodies.

Nasopharyngeal Panbio COVID-19 Antigen Performed at Point-of-Care Has a High Sensitivity in Symptomatic and Asymptomatic Patients With Higher Risk for Transmission and Older Age.

BACKGROUND: Performance of point-of-care tests in different clinical scenarios and on different samples remains undetermined. We comprehensively evaluated the performance of the nasopharyngeal Panbio COVID-19 Ag Rapid Test Device. METHODS: This is a prospective study that includes consecutive patients attending 3 primary care centers (PCCs) and an emergency department. The antigen test was performed at point-of-care in nasopharyngeal and nasal swabs and in saliva. Positive percent agreement (PPA) and negative percent agreement (NPA) were calculated with the reverse-transcription polymerase chain reaction (RT-PCR) assay as reference standard. RESULTS: Of 913 patients included, 296 (32.3%) were asymptomatic and 690 (75.6%) came from the PCC. Nasopharyngeal swabs were collected from 913 patients, nasal swabs were collected from 659 patients, and saliva was collected from 611 patients. The RT-PCR was positive in 196 (21.5%) nasopharyngeal samples (NPS). Overall, PPA (95% CI) in NPS was 60.5% (53.3-67.4), and it was lower in nasal swabs (44.7%) and saliva (23.1%). Test performance in NPS was largely dependent on the cycle threshold (Ct) in RT-PCR, with PPA of 94% for Ct ≤25 and 80% for Ct <30. In symptomatic patients, the PPA was 95% for Ct ≤25, 85% for Ct <30, and 89% for the symptom triad of fever, cough, and malaise. Performance was also dependent on age, with a PPA of 100% in symptomatic patients >50 years with Ct <25. In asymptomatic patients, the PPA was 86% for Ct <25. In all cases, NPA was 100%. CONCLUSIONS: The nasopharyngeal Panbio COVID-19 Ag test performed at point-of-care has a good sensitivity in symptomatic patients with Ct <30 and older age. The test was useful to identify asymptomatic patients with lower Ct values.

SARS-CoV-2 Seroconversion and Viral Clearance in Patients Hospitalized With COVID-19: Viral Load Predicts Antibody Response.

BACKGROUND: The interdependencies of viral replication and the host immune response in patients with coronavirus disease 2019 (COVID-19) remain to be defined. We investigated the viral determinants of antibody response, the predictors of nonseroconversion, and the role of antibodies on viral dynamics. METHODS: This was a prospective study in patients hospitalized with COVID-19 that was microbiologically confirmed by real-time polymerase chain reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies (total and S-IgG/N-IgG), respectively. RESULTS: Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1-Q3) of 11 (8-14) days. The median (Q1-Q3) follow-up was 74.5 (63.0-87.0) days. In an adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (P = .009) and positively with time to viral clearance (P = .004). Adjusted predictors of S-IgG levels were time to viral clearance (P < .001), bilateral lung infiltrates on admission (P = .011), and the time-dependent SARS-CoV-2 RNA (P < .001) and SARS-CoV-2 RNA area under the curve (P = .001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; P < .001), had shorter time to viral clearance (3.0 vs 41.0; P < .001), and were more likely to have SARS-CoV-2 only detected on fecal samples (P < .001). Nonseroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity. CONCLUSIONS: Viral replication determines the magnitude of antibody response to SARS-CoV-2, which, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.

Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold (CT ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at CT values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions.

Preemptive interleukin-6 blockade in patients with COVID-19.

Excessive interleukin-6 signaling is a key factor contributing to the cytokine release syndrome implicated in clinical manifestations of COVID-19. Preliminary results suggest that tocilizumab, a humanized monoclonal anti-interleukin-6 receptor antibody, may be beneficial in severely ill patients, but no data are available on earlier stages of disease. An anticipated blockade of interleukin-6 might hypothetically prevent the catastrophic consequences of the overt cytokine storm. We evaluated early-given tocilizumab in patients hospitalized with COVID-19, and identified outcome predictors. Consecutive patients with initial Sequential-Organ-Failure-Assessment (SOFA) score < 3 fulfilling pre-defined criteria were treated with tocilizumab. Serial plasma biomarkers and nasopharyngeal swabs were collected. Of 193 patients admitted with COVID-19, 64 met the inclusion criteria. After tocilizumab, 49 (76.6%) had an early favorable response. Adjusted predictors of response were gender, SOFA score, neutrophil/lymphocyte ratio, Charlson comorbidity index and systolic blood pressure. At week-4, 56.1% of responders and 30% of non-responders had cleared the SARS-CoV-2 from nasopharynx. Temporal profiles of interleukin-6, C-reactive protein, neutrophil/lymphocyte ratio, NT-ProBNP, D-dimer, and cardiac-troponin-I differed according to tocilizumab response and discriminated final in-hospital outcome. No deaths or disease recurrences were observed. Preemptive therapy with tocilizumab was safe and associated with favorable outcomes in most patients. Biological and clinical markers predicted outcomes.

Impact of interleukin-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and antibody responses in patients with COVID-19: A prospective cohort study.

BACKGROUND: The virological and immunological effects of the immunomodulatory drugs used for COVID-19 remain unknown. We evaluated the impact of interleukin (IL)-6 blockade with tocilizumab on SARS-CoV-2 viral kinetics and the antibody response in patients with COVID-19. METHODS: Prospective cohort study in patients admitted with COVID-19. Serial nasopharyngeal and plasma samples were measured for SARS-CoV-2 RNA and S-IgG/N-IgG titers, respectively. FINDINGS: 138 patients with confirmed infection were included; 76 (55%) underwent IL-6 blockade. Median initial SOFA (p = 0•016) and SARS-CoV-2 viral load (p<0•001, Mann-Whitney-Wilcoxon test) were significantly higher among anti-IL-6 users. Patients under IL-6 blockade showed delayed viral clearance in the Kaplan-Meier curves (HR 0•35 [95%CI] [0•15-0•81], log-rank p = 0•014), but an adjusted propensity score matching model did not demonstrate a significant relationship of IL-6 blockade with viral clearance (HR 1•63 [0•35-7•7]). Cox regression showed an inverse association between SARS-CoV-2 RNA clearance and the initial viral load (HR 0•35 [0•11-0•89]). Patients under the IL-6 blocker showed shorter median time to seropositivity, higher peak antibody titers, and higher cumulative proportion of seropositivity in the Kaplan Meier curves (HR 3•1 [1•9-5] for S-IgG; and HR 3•0 [1•9-4•9] for N-IgG; log-rank p<0•001 for both). However, no significant differences between groups were found in either S-IgG (HR 1•56 [0•41-6•0]) nor N-IgG (HR 0•96 [0•26-3•5]) responses in an adjusted propensity score analysis. INTERPRETATION: Our results suggest that in patients infected with SARS-CoV-2, IL-6 blockade does not impair the viral specific antibody responses. Although a delayed viral clearance was observed, it was driven by a higher initial viral load. The study supports the safety of this therapy in patients with COVID-19. FUNDING: Instituto de salud Carlos III (Spain).

Infection With Chlamydia trachomatis Increases the Risk of High-grade Anal Intraepithelial Neoplasia in People Living With Human Immunodeficiency Virus.

BACKGROUND: We aimed to assess the relationship between sexually transmitted infections (STIs)-including a large panel of human papillomavirus (HPV) genotypes-and high-grade anal intraepithelial neoplasia (HGAIN) in men who have sex with men (MSM) who were living with human immunodeficiency virus (HIV). METHODS: In a prospective study in an HIV cohort, participants underwent high-resolution anoscopy (HRA) for anorectal swabs collection to investigate STIs and for anal biopsy. Multiplex real-time polymerase chain reactions were performed, detecting several STIs and 28 HPV genotypes. Univariate and multivariate generalized linear models were used to analyze the relationships of variables of interest with HGAIN. RESULTS: There were 145 participants included; in 49, 2 HRAs were performed. Ureaplasma urealyticum (UU) was detected in 25 (17.2%) participants, Chlamydia trachomatis (CT) in 13 (9.0%), Mycoplasma genitalium (MG) in 4 (2.8%), HPV16 in 38 (26.2%), HPV52 in 29 (20%), and HPV53 and HPV42 in 28 (19.3%) participants each. There were 35 (24.1%) subjects diagnosed with HGAIN. In the univariate analysis, HGAIN was associated with CT, UU, MG, HPV16, HPV53, HPV68, and HPV70, and significant interactions were found between CT and HPV16 (odds ratio [OR] 31.0 95% confidence interval [CI] 4.3-221.7) and between UU and HPV16 (OR 8.8, 95% CI 2.1-37.5). In the adjusted model, CT, HPV16, HPV53, HPV70, the CD4+/CD8+ ratio, and the interaction between CT and HPV16 remained independent predictors of HGAIN. HPV16, HPV53, and HPV70 persisted in the second HRA in all the participants with recurrent HGAIN. CONCLUSIONS: Coinfection with CT may potentiate the oncogenic capability of HPV16 and increase the risk of HGAIN in people with HIV. HPV53 and HPV70 should be considered among the genotypes associated with HGAIN.

Rectal and seminal HIV-1 RNA decay towards virological suppression in infected MSM initiating dolutegravir/abacavir/lamivudine.

BACKGROUND: The time at which the protective effect of starting ART is achieved in male rectal and genital reservoirs is not clearly established. OBJECTIVES: To quantify HIV-1 RNA decay towards virological suppression in rectal mucosa and semen in MSM starting dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). METHODS: A longitudinal cohort study of ART-naive HIV-positive MSM was performed. HIV-1 RNA was quantified in rectal mucosa and seminal plasma samples at day 1 of ART initiation (baseline) and every 4 weeks until week 20 (w20; all participants) and week 64 (w64; 6 of 12 participants). RESULTS: Twelve MSM, with median (IQR) age 36 (33-40) years and baseline CD4+ count 449 (411-503) cells/mm3, were included. At baseline, HIV-1 RNA was detectable in all plasma and seminal samples and 10/12 rectal samples. All participants achieved plasma virological suppression by w20, whereas HIV-1 RNA was detectable in 42% and 50% of seminal and rectal samples, respectively. At w64, HIV-1 RNA was detectable in 1/6 seminal and 1/6 rectal samples. A relationship of baseline seminal and rectal HIV-1 RNA levels with viral shedding in reservoirs (HIV-1 RNA >200 copies/mL or copies/swab) was found. In addition, a significant association of baseline plasma viral load with time to rectal HIV-1 RNA <200 copies/swab was found (P=0.025). CONCLUSIONS: Viral decay after initiating DTG/ABC/3TC is slower in rectal mucosa and semen than in plasma. Approximately half of patients achieved undetectable HIV-1 RNA levels in rectal and genital secretions at w20 and in some patients viral shedding persisted for up to 1 year. Initial plasma viral load influences time to rectal suppression.