Undetectable HIV RNA Research Articles

Antiretroviral Therapy in HIV Controllers Reduces Immune Activation and Exhaustion

HIV controllers are people who have low or undetectable HIV RNA levels without taking antiretroviral therapy (ART). Even though these individuals

Neurocognitive impairment is worse in HIV/HCV-coinfected individuals with liver dysfunction.

Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons range from 40 to 63% but its correlates have not been described. In this study, we examined HIV/HCV-coinfected adults on antiretroviral therapy (ART) with undetectable HIV RNA in blood (n = 412) who were assessed using a comprehensive neuropsychological test battery. Demographics, host and viral biomarkers, and markers of liver dysfunction were compared between impaired (n = 198) and unimpaired (n = 214) participants using logistic regression. The cohort was predominantly middle-aged men, half of whom (48%) had NCI. The odds of NCI increased by almost two-fold when serum albumin was < 4g/dL, 1.7-fold when alanine aminotransferase (ALT) levels were > 50IU/L, and 2.2-fold with every unit increase in log10 AST to Platelet Ratio Index (APRI). These readily available clinical biomarkers of NCI measure hepatic injury and/or dysfunction, suggesting a mechanism for the effects of HCV infection on NCI. They may identify patients at increased risk of NCI who could be prioritized for early initiation of HCV treatment to protect or improve cognition.

Viro-immunological efficacy and tolerability of dolutegravir-based regimens compared to regimens based on other integrase strand inhibitors, protease inhibitors or non-nucleoside reverse transcriptase inhibitors in patients with acute HIV-1 infection: A multicenter retrospective cohort study

ObjectivesThe aim of this study was to compare the tolerability and viro-immunological efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI or NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI). MethodsAll patients diagnosed with AHI and on antiretroviral therapy (ART) between January 2015 and December 2017 from five centers in Italy were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot. ResultsForty-three patients were enrolled: 20 in the DTG group, 23 in the NODTG group. Nine patients (20.9%; four in the DTG group, five in the NODTG group) were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% were male, with a median age of 41 years (interquartile range [IQR] 31-48). Median time between HIV diagnosis and ART initiation was 12 days (IQR 5-28). Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all were in the DTG group (P=0.005). All patients had undetectable HIV-RNA at the end of follow-up except two patients, one of whom had 57 copies and one who was lost to follow-up. In Kaplan-Meier analysis, time to virological suppression was similar in the two groups (log rank: P= 0.7155). After achieving virological suppression, four patients stopped ART because of toxicity: two on DTG, two on EVG for neurological and gastrointestinal toxicity, respectively. ConclusionIn our setting, ART in AHI is started very early. DTG showed good viro-immunological efficacy even in the presence of NRTI-transmitted mutations. DTG interruptions were rare.

Frailty in medically complex individuals with chronic HIV.

Multimorbidity and frailty are consequences of aging with HIV, yet not everyone with medical disease is frail. Our objective was to identify factors associated with frailty in a multimorbid HIV-infected cohort. Analysis of a prospective, observational, longitudinal cohort. Three hundred and thirty-two participants in the medically advanced National NeuroAIDS Tissue Consortium (NNTC) study were categorized as frail, prefrail, or robust with the Fried Frailty Index. A series of logistic regression analyses (first univariate, then multivariable) were conducted to determine whether medical comorbidities, immunologic and virologic parameters, and/or neuropsychiatric variables predicted increased odds of frailty. The mean number of medical comorbidities per participant was 2.7, mean CD4 T-cell count was 530 cells/μl, and 77% had undetectable HIV RNA in blood. Twenty-two percent were frail, 55% prefrail, and 23% robust. Significant predictors of frailty in multivariable analysis were cognitive diagnosis rendered by Frascati criteria, depressive symptoms, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and sex. Men were less likely to be frail than women. Higher odds of frailty were seen with: symptomatic, but not asymptomatic, cognitive impairment (compared with cognitive normals); more depressive symptoms; diabetes mellitus; and COPD. Neuropsychiatric illness increased odds of being frail on a predominantly physical/motoric measure, but only when symptomatic. Lack of association with asymptomatic impairment may reflect the importance of functional limitation to frailty, or possibly a unique resilience phenotype. Understanding why sex and symptomatic neuropsychiatric illness are associated with frailty will be important in managing HIV-associated morbidity in aging populations.

Advanced Glycation End Products Are Associated With Inflammation and Endothelial Dysfunction in HIV.

To compare levels of advanced glycation end products (AGEs) between HIV-infected patients and uninfected controls and assess the relationship between AGEs, HIV, inflammation, and endothelial dysfunction. Cross-sectional study involving 90 individuals (68 HIV+ and 22 healthy controls matched by age and sex). AGE levels were assessed using 3 different modalities: free AGEs were measured in the serum, skin autofluorescence (AF) was determined with a noninvasive reader, and dietary AGEs were estimated using 24-hour dietary recalls. Markers of inflammation, immune activation, and endothelial dysfunction were also measured. Wilcoxon rank-sum and χ tests were used to compare AGEs between groups. Spearman correlations were used to explore relationships between variables while adjusting for different covariates. Overall, 71% were men and 68% were African American, with a median age of 53 years. Among HIV-infected individuals, all participants were on antiretroviral therapy by design, and most participants (78%) had an undetectable HIV-1 RNA level (≤20 copies/mL). Skin AF and serum AGEs were significantly higher in HIV-infected participants compared with uninfected controls (P < 0.01), whereas no differences in dietary AGEs were found between groups (P = 0.2). In the HIV-infected group, but not in controls, skin AF and circulating AGEs were significantly associated with inflammatory and oxidative markers, and with markers of endothelial dysfunction. These results suggest intrinsic production of AGE in HIV-infected individuals. The relationship between serum/skin AGE and inflammatory, oxidative, and cardiovascular markers highlights the potential implications of AGEs in chronic inflammation and endothelial dysfunction in HIV, suggesting a new potential target for HIV-associated heightened inflammation and cardiovascular risk.

Immunological profiles of HIV-positive recipients of liver transplant

BackgroundScarce data are available about immune cell frequencies in HIV-positive recipients of liver transplant. Alterations in immune subsets can lead to persistent immune activation and disease progression or reduced HIV-specific responses. In liver transplantation, impaired immune tolerance can lead to organ rejection. MethodsHIV-positive subjects with undetectable HIVRNA and CD4 > 100/mm3 were included. Control groups were non-transplanted HIV-positive patients with similar immunovirological parameters and healthy subjects. B cells (memory, transitional, and mature subsets), T cells (effector TH1, nonclassic TH1, TH17, TH1/17; T regulatory naïve and effector subsets and CD8+ T regulatory cells), and NK cells (CD56dim and CD56bright subsets) were analyzed by flow cytometry. ResultsA total of 56 patients, including 14 HIV-positive transplant recipients (HIV-LT), 14 HIV-positive controls, and 28 healthy controls were included. Median age of HIV-LT patients was 54.9 years with median time from transplant of 7.6 years. Eleven (79%) were HIV/HCV coinfected. Compared to nontransplanted patients, HIV-LT displayed significantly increased frequency of T CD8+ cells, lower percentage of T CD4+ cell, and lower number of nonclassic TH1, TH1/17 cells and naïve T CD4+ regulatory cells (Tregs). Healthy controls showed increased numbers of B cell subsets and decreased percentage of T effector subpopulations compared to HIV-LT. Compared to HIV-positive patients, healthy controls had higher B cells, NK cells, CD4+ T cells, naïve CD4+ Tregs but lower CD8+ T cells, effector Tregs, CD8+ Tregs, and all T effector cell subsets. ConclusionsImmune cell subpopulations potentially associated with HIV progression and organ rejection were detected in HIV-positive transplant recipients. We confirmed altered frequencies of B, T, and NK cell populations in HIV-positive liver transplant recipients compared to healthy controls. The imbalance among immune cell subsets deserves further studies to identify markers of transplant outcome and potential therapeutic targets.

Brief Report: Response to Hepatitis A Virus Vaccine in HIV-Infected Patients Within a Retrospective, Multicentric Cohort: Facing Hepatitis A Outbreaks in the Clinical Practice.

Various recent outbreaks of hepatitis A virus (HAV) have been described in men who have sex with men despite the availability of an effective vaccine. This study aimed to determine the current rates of seroconversion after receiving HAV vaccine (HAV-V) in HIV-infected patients under real-life conditions. Patients were selected from a Southern Spanish multicentric cohort of HIV-infected subjects. Retrospective analysis of all patients who received 2 doses (standard scheme) from April 2008 to May 2016 or from June 2016 to February 2018 facing an HAV outbreak with shortage of HAV-V, 1 single dose of HAV-V. Response to HAV-V was defined as positive anti-HAV IgG between 1 and 12 months after the last vaccination dose. A total of 522 patients were included, mainly men who have sex with men (86.2%). In the standard-dose group, 303/343 [88.3%; 95% confidence interval (CI): 84.5 to 91.5] patients showed seroconversion as compared with 149/179 (83.2%; 95% CI: 76.9 to 88.4) of the single-dose group (P = 0.107). Undetectable baseline HIV-RNA (adjusted odds ratio: 4.86; 95% CI: 1.86 to 12.75; P = 0.001) and a CD4 T-cell count ≥350/μL (adjusted odds ratio, 3.96; 95% CI: 1.26 to 12.49; P = 0.019) were independently associated with response to both regimens. A higher CD4/CD8 ratio was also associated with response after a single dose. HIV-infected patients should be encouraged to undergo HAV-V with 2 standard doses 6 months apart; a single dose achieves a high rate of seroconversion in those patients with favorable response factors and may be enough to limit future outbreaks in case of HAV-V shortage until supply is reestablished.

Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

Anti-gp41 antibody levels reflect HIV viral suppression and cellular reservoir in long-term antiretroviral-treated trial participants.

A major challenge to HIV cure strategies is the quantification of persistent reactivation-prone virus in people living with HIV. To determine whether anti-gp41 antibody levels correlate with viral suppression and HIV-1 DNA levels in patients on ART. Participants with plasma HIV-1 RNA below 50 copies/mL for >12 months were included from three ANRS cohorts (COPANA, MONOI and APROCO). Antibody levels to gp41 were measured by a low-sensitivity enzyme-linked immunoassay. Correlations with patient and virus characteristics, plasma HIV-1 RNA load (standard and ultrasensitive tests) and cell-associated HIV-1 DNA were assessed. Median age was 41 years and 77.5% of the 683 participants were men. Median CD4+ T cell count was 582 cells/mm3 and median viral suppression duration was 6.6 years (IQR 2.0-9.5). The overall median anti-gp41 antibody titre was 1.3 (IQR 0.6-1.9); median HIV-1 DNA level was 2.6 (IQR 2.1-3.0) log10 copies/106 leucocytes; and HIV-1 RNA was undetectable in 56% of samples. A lower titre of anti-gp41 antibodies correlated with male gender, longer viral suppression and lower HIV-1 DNA burden. Sustained undetectable HIV-1 RNA was associated with lower anti-gp41 levels [median 1.1 (IQR 0.5-1.6) versus 1.4 (IQR 0.7-1.9), P = 0.009]. Anti-gp41 levels decreased with the duration of antiviral suppression on ART. Lower titres were associated with lower HIV-1 DNA levels and longer duration of viral suppression, reflecting minimal antigen stimulation. Anti-gp41 antibody titration may be a useful biomarker reflecting long-term HIV-1 suppression on ART.

Illicit massive silicone injections always induce chronic and definitive silicone blood diffusion with dermatologic complications.

Male-to-female transgender (MtF TG) individuals often report using illegal subcutaneous silicone injections for body feminisation. It leads to silicone dissemination and various dermatologic complications.We report the long-term complications of these feminisation procedures with blood smear examination and dermatologic examination.Between July 2015 and December 2015, 77 MtF TG consulting at Bichat Hospital (Paris, France) were included in this cross-sectional study. Blood smear examinations were performed by a trained haematologist to quantify the presence of silicone vacuoles in monocytes.All patients reported a history of massive amounts of silicone injections (mean 4 L, range 0.5–15 L). Most patients were South American (75/77, 97%). Fifty-nine (59/75, 79%) were HIV-seropositive, mostly with undetectable HIV RNA plasma levels (46/58, 80%). Clinical examinations reported dermatologic complications for all patients: lymphatic or subcutaneous migration of silicone (59%), inflammation (50%), varicose veins (39%), post-inflammatory pigmentation (20%), infection (14%) and abscesses (4%). Blood smear examination showed intracytoplasmic vacuoles containing silicone in monocytes in all patients.We did not chemically prove the silicone nature of the vacuoles. The design of this study does not allow evaluation of short-term complications that should not be minimized.Illicit massive silicone injections always induced chronic and definitive silicone blood diffusion with dermatologic complications. This study highlights the dangers and the inefficiency of clandestine esthetic surgery. There is a need for targeted information campaigns with transgender populations about silicone injections. Otherwise, these practices may persist.

Influence of HIV Infection on the Natural History of Hepatocellular Carcinoma: Results From a Global Multicohort Study.

Conflicting evidence indicates that HIV seropositivity may influence the outcome of patients with hepatocellular carcinoma (HCC), a leading cause of mortality in people with HIV. We aimed to verify whether HIV affected the overall survival (OS) of patients with HCC, independent of treatment and geographic origin. We designed an international multicohort study of patients with HCC accrued from four continents who did not receive any anticancer treatment. We estimated the effect of HIV seropositivity on patients' OS while accounting for common prognostic factors and demographic characteristics in uni- and multivariable models. A total of 1,588 patients were recruited, 132 of whom were HIV positive. Most patients clustered within Barcelona Clinic Liver Cancer (BCLC) C or D criteria (n = 1,168 [74%]) and Child-Turcotte-Pugh (CTP) class B (median score, 7; interquartile range [IQR], 3). At HCC diagnosis, the majority of patients who were HIV-positive (n = 65 [64%]) had been on antiretrovirals for a median duration of 8.3 years (IQR, 8.59 years) and had median CD4+ cell counts of 256 (IQR, 284) with undetectable HIV RNA (n = 68 [52%]). OS decreased significantly throughout BCLC stages 0 to D (16, 12, 7.5, 3.1, and 3 months, respectively; P < .001). Median OS of patients who were HIV-positive was one half that of their HIV-uninfected counterparts (2.2 months [bootstrap 95% CI, 1.2 to 3.1 months] v 4.1 months [95% CI, 3.6 to 4.4 months]). In adjusted analyses, HIV seropositivity increased the hazard of death by 24% ( P = .0333) independent of BCLC ( P < .0001), CTP ( P < .0001), α-fetoprotein ( P < .0001), geographical origin ( P < .0001), and male sex ( P = .0016). Predictors of worse OS in patients who were HIV-positive included CTP ( P = .0071) and α-fetoprotein ( P < .0001). Despite adequate antiretroviral treatment, HIV seropositivity is associated with decreased survival in HCC, independent of stage, anticancer treatment, and geographical origin. Mechanistic studies investigating the immunobiology of HIV-associated HCC are urgently required.

558. Genotype-Guided vs. Standard First-line Antiretroviral Regimen for Treatment Naïve HIV-Infected Patients in Thailand: A Prospective Randomized Controlled Trial

BackgroundAn increase in the prevalence of pretreatment drug resistance (PDR) has been reported among HIV-infected individuals and PDR may be associated with poor treatment outcome of first-line antiretroviral therapy (ART). However, drug resistance testing prior to ART initiation is not routinely performed in resource-limited settings. We aimed to evaluate the prevalence of PDR in Thailand and whether genotype-guided first-line ART can improve treatment outcomes.MethodsA prospective, multicenter, randomized, controlled trial was conducted involving newly diagnosed HIV-infected adults. Participants who were going to initiate ART were randomly assigned to either genotype-guided (GG) group or standard of care (SC) group with 1:1 allocation as per a computer-generated randomization. Genotypic resistance assay was performed in all participants. The investigators in GG group were informed the results of genotypic resistance assays before selecting the ART regimen. In contrast, the results of SC group were blinded to the investigators. Factors associated with having PDR and undetectable HIV RNA were analyzed by logistic regression.ResultsA total of 153 participants were randomized to either GG group (78 participants) SC group (75 participants). Of all, median (IQR) age was 32 (26–42) years and 83% were male. Median (IQR) CD4 count was 190 (42–324) cells/mm3. Overall prevalence of PDR was 13.7% and NNRTIs PDR was 10.5%. The most common mutation was V179D (5.9%), T215Y (3.9%) and E138K (2.0%). No associated factor of having PDR was determined. At 24 weeks, 85.9% in GG group and 86.3% in SC group had undetectable HIV RNA (P = 0.940). By univariate logistic regression, having PDR was not associated with undetectable HIV RNA (OR 0.40; 95% CI 0.12–1.30, P = 0.122). By multiple logistic regression, factors associated with undetectable HIV RNA were adherence (OR 1.53 per 5% increment; 95% CI 1.15–2.05; P = 0.004) and no history of PJP (OR 6.24; 95% CI 1.62–24.08; P = 0.008).ConclusionIn Thailand, the prevalence of PDR is moderate and NNRTIs PDR is high according to the WHO category. Recommended first-line ART for Thai HIV-infected patients should be modified. Routine genotype-guided first-line ART is not now recommended in Thailand. Periodically PDR surveillance and cost-effectiveness study of genotype-guided first-line ART should be further studied. Disclosures All authors: No reported disclosures.

2252. Predictors of Cardiovascular Outcomes in Older HIV-Infected Patients: CORE50 Cohort 10-Year Follow-up

BackgroundCardiovascular (CV) disease is increasingly recognized in HIV+ patients. Currently there are limited data on older HIV+ patients in regards to CV outcomes. The CORE50 study was a cross-sectional study of 121 HIV+ patients ≥ 50 years (83% African American) recruited 2005–2006 at the CORE Center. The goal of this study was to identify predictors of CV outcomes and the impact of the Framingham cardiac risk at baseline on CV outcomes and mortality >10 years later.MethodsRetrospective chart review was conducted in 2018 to evaluate HAART therapy, CD4, viral suppression, HCV coinfection or treatment history, comorbid conditions, BMI, renal function and current medications. Patients were evaluated for CV events (defined as myocardial infarction, cerebrovascular events, transient ischemic attacks and peripheral artery disease).ResultsAt follow-up, 60 (49%) patients with a mean age of 65 years remained in care at CORE. Mean CD4 count was 529 cells/mm3 and 82% had undetectable HIVRNA. 22 patients had died (18%), 10(8%) had transferred care and 29(24%) lost to follow-up. The mean age at death was 61 years. The causes of death were CV (18.2%), cancer (36.4%), infection (18.5%) and other (27.2%; organ failure/overdose/unknown). On Univariate analysis, Framingham cardiac risk (FCR) of >10% at baseline (2005/2006) was associated with increased CV events (P = 0.05). FCR >20% was associated with increased death (P = 0.01). Smoking at baseline and follow-up were associated with increased CV events (P = 0.05 and P = 0.035, respectively). Evaluation of medication regimen showed history of protease inhibitor use or current use of integrase inhibitor was associated with increased CV events (P = 0.01 and P = 0.011, respectively). History of depression was associated with increased CV events (P = 0.035). Aspirin use at initial assessment was associated with decreased death (P < 0.000).ConclusionThis retrospective study shows that FCR, history of depression and smoking are associated with adverse outcomes in HIV patients. It suggests that the FCR is useful for risk stratification of cardiovascular disease in HIV patients. It is extremely important to identify and manage cardiac risk factors in older HIV patients to reduce cardiovascular morbidity and mortality.Disclosures All authors: No reported disclosures.

603. Multi-morbidity and Impaired CD4/CD8 Ratios in Older Adults with Well-Controlled HIV

BackgroundOlder age has been associated with impaired CD4 recovery and a low CD4:CD8 ratio is an independent predictor of non-AIDS morbidity/mortality. In this study we describe the overall comorbidity burden and assess factors associated with CD4:CD8 <1 among HIV+ older adults 60 years+ seen at CORE Center, Cook County Health and Hospital System; a safety-net health system.MethodsWe evaluated demographic, clinical, and lab variables in all HIV+> 60 years who had at least 1 primary care visit from January 1, 2016 to May 31, 2017 at the RMR CORE center. Since HIV viremia is associated with CD4 recovery, analysis on CD4:CD8 ratios was restricted to the patients with viral suppression.ResultsThere were 809 patients with a median age of 63 (range: 60–89) years. Seventy-five percent were male, 74% black, 17% Hispanic and 8% white. Mean CD4 was 538 (+307) cells/mm; 107 (13%) had CD4 < 200 and 675 (84%) had undetectable HIVRNA (<40 copies/mL). 38% were HCV Ab+. Common comorbidities were hypertension 62%, COPD 23%, diabetes 22%, depression 17%, osteoarthritis 15%, neuropathy, chronic kidney disease (CKD) and coronary artery disease (CAD) 13% each. 50% had 1–2 comorbidities and 31% had >3 co-morbidities. Of the 675 patients with suppressed viremia, 470 patient (70%) had CD4:CD8 <1 and 245 (36%) had CD4:CD8 <0.5. Compared with patients with CD4:CD8 >1, patient with CD4:CD8 <1 had lower CD4 counts (451 vs. 739 cells/mm3; P < 0.001), were less likely to have CD4 > 500 (35% vs. 75%; P <0.001), more likely to have CD4 <200 (13% vs. 1%; P <0.001), be male (82% vs. 60%; P < 0.001), HCVab+ (39% vs. 32%; P 0.05). They also trended to have more CAD 7% vs. 4% (P = 0.1) and more CKD 15% vs. 11% (P = 0.2).ConclusionThere was a high rate of multi-morbidity among older, predominantly ethnic minorities HIV-infected adults with 56% having >2 comorbidities. In the setting of viral suppression, 70% still had a CD4:CD8 ratio <1 which likely reflects the effects of older age, and lower CD4 nadir. This impaired immune restoration and co-morbidity burden portend a higher risk of non-AIDS morbidity and mortality in these patients and highlights the need for comprehensive care in HIV clinic settings.Disclosures All authors: No reported disclosures.

HIV-RNA decay in paired blood and semen samples of subjects receiving their first dolutegravir-based ART regimen

Background and objectivesWe aimed to investigate to what extent a first-line DTG-based ART regimen reduces HIV-RNA in semen compared to plasma. Study designIn this prospective, observational study, ART-naïve, HIV-infected males starting their first ART regimen with DTG plus TDF/FTC or ABC/3TC were enrolled. Paired blood (BP) and seminal plasma (SP) samples were collected at baseline (T0) and at week-2/4/12/24 after ART initiation. Sexually transmitted infections (STI) were ruled out before enrolment. ResultsMedian baseline HIV-RNA levels were lower in SP compared to BP (657 versus 38.200 copies/ml, p < 0.001), three subjects had undetectable semen HIV-RNA. After 12 weeks of treatment, HIV-RNA was below the quantification limit in both BP and SP of 11 pts (61.1%). Discordant results were obtained in 6 subjects (33.3%), showing quantifiable HIV-RNA in blood only (2 cases) and in semen only (4 cases). Finally, one subject had a positive HIV-RNA in SP/BP. At W24, only in 2/16 subjects (12.5%) HIV-RNA was detectable in semen, while in the others it was negative on SP/BP. No concurrent STI was found in subjects with detectable VL in semen. ConclusionsDTG demonstrated effectiveness in reducing VL with different kinetics in blood and semen, despite seminal viral suppression after 6 months of ART was not obtained in the totality of subjects.

Dolutegravir-rilpivirine: first 2-drug regimen for HIV-positive adults

ABSTRACTIntroduction: New strategies for HIV treatment are being investigated to reduce drug-exposure, toxicities, and costs. Dolutegravir (DTG) 50 mg/rilpivirine (RPV) 25 mg was approved in November 2017 by FDA and in May 2018 by the European Medicines Agency (EMA). It is indicated as a complete regimen for HIV-1 infected adults with undetectable plasmatic HIV-RNA for at least 6 months on their current HIV treatment combination. Its approval was based on the data of two randomized, multicenter, non-inferiority trials (SWORD-1 and SWORD-2).Areas covered: We reviewed data from literature about DTG and RPV. We mainly focused on the efficacy and on the safety of this new dual therapy. Its impact on renal function, its bone and cardiovascular profile, its reservoir penetration and its role on inflammation were also evaluated.Expert commentary: Dual therapies may be an attractive alternative to standard triple regimens in terms of tolerability and simplicity. Long-term efficacy of DTG and RPV dual regimen need to be confirmed, where only the extensive use of this new treatment and a longer follow-up will give us the answers.

Previous incarceration impacts access to hepatitis C virus (HCV) treatment among HIV-HCV co-infected patients in Canada.

IntroductionThe prevalence of hepatitis C virus (HCV) is far higher in prison settings than in the general population; thus, micro‐elimination strategies must target people in prison to eliminate HCV. We aimed to examine incarceration patterns and determine whether incarceration impacts HCV treatment uptake among Canadian HIV‐HCV co‐infected individuals in the direct‐acting antiviral (DAA) era.MethodsThe Canadian Co‐Infection Cohort prospectively follows HIV‐HCV co‐infected people from 18 centres. HCV RNA‐positive participants with available baseline information on incarceration history were included and followed from 21 November 2013 (when second‐generation DAAs were approved by Health Canada) until 30 June 2017. A Cox proportional hazards model was used to assess the effect of time‐updated incarceration status on time to treatment uptake, adjusting for patient‐level characteristics known to be associated with treatment uptake in the DAA era.ResultsOverall, 1433 participants (1032/72% men) were included; 67% had a history of incarceration and 39% were re‐incarcerated at least once. Compared to those never incarcerated, previously incarcerated participants were more likely to be Indigenous, earn <$1500 CAD/month, report current or past injection drug use and have poorly controlled HIV. There were 339 second‐generation DAA treatment initiations during follow‐up (18/100 person‐years). Overall, 48% of participants never incarcerated were treated (27/100 person‐years) compared to only 31% of previously incarcerated participants (15/100 person‐years). Sustained virologic response (SVR) rates at 12 weeks were 95% and 92% respectively. After adjusting for other factors, participants with a history of incarceration (adjusted hazard ratio (aHR): 0.7, 95% CI: 0.5 to 0.9) were less likely to initiate treatment, as were those with a monthly income <$1500 (aHR: 0.7, 95% CI: 0.5 to 0.9) or who reported current injection drug use (aHR: 0.7, 95% CI: 0.4 to 1.0). Participants with undetectable HIV RNA (aHR: 2.1, 95% CI: 1.6 to 2.9) or significant fibrosis (aHR: 1.5, 95% CI: 1.2 to 1.9) were more likely to initiate treatment.ConclusionsThe majority of HIV‐HCV co‐infected persons had a history of incarceration. Those previously incarcerated were 30% less likely to access treatment in the DAA era even after accounting for several patient‐level characteristics. With SVR rates above 90%, HCV elimination may be possible if treatment is expanded for this vulnerable and neglected group.

Abacavir/lamivudine/dolutegravir single tablet regimen in patients with human immunodeficiency virus and end-stage renal disease on hemodialysis.

No single-tablet antiretroviral (ARV) regimens (STRs) are approved for patients with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) on hemodialysis (HD). Based on known pharmacokinetic (PK) properties, abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) STR may represent a promising option. This case series presents the safety and efficacy of ABC/3TC/DTG STR in patients with HIV and ESRD on HD. Patients were included if they were HIV-positive, maintained on intermittent HD for ESRD, switched to an ARV regimen containing ABC/3TC/DTG, and had at least one set of virologic data before and after the switch. Average age (±standard deviation) was 59 (±8) years. The majority of patients were cis-gender male and non-Hispanic Black. Only one demonstrated clinically significant resistance at baseline. All were on multiple-tablet regimens prior to the switch. Five patients (83%) achieved undetectable HIV-RNA after the switch while only four patients (46%) were undetectable immediately prior. No decline in immune function was noted. ABC/3TC/DTG STR was well tolerated. Only one patient self-reported an adverse event (nausea), which resolved without drug discontinuation. Based on these data, it appears that ABC/3TC/DTG may be a safe and effective ARV-STR option for patients with HIV and ESRD on HD. A larger trial including a PK analysis is needed to confirm these findings.

Incident genital HPV infections and potential impact of HPV vaccines in adult women living with HIV/AIDS

ABSTRACT This study aims to describe and characterize incident HR-HPV infections and associated diseases in HIV-infected women. 805 HIV-infected women enrolled in the VALHIDATE Study were screened and followed-up for HPV by co-testing. Social, behavioral and health data were collected. HPV-DNA positive samples were typed using a commercial kit or RFLP analysis. Conventional Pap-smears were evaluated using the 2001 Bethesda System. The participants with abnormal cytological results were referred for colposcopy. 565 HIV-infected women (median age: 43 years) were analysed, 40.9% had >5 lifetime sexual partners, 77.2% contracted HIV through sexual intercourse, 93% were receiving antiretroviral treatment and 77.3% had undetectable HIV-RNA. The women underwent 1254 follow-ups (median follow-up: 33 months) for 1430.6 PersonYear-Follow-Up. 37.4% of baseline HPV-negative women acquired incident HPV-infections, 69.6% of which were HR-HPVs. HPV-53 was the most common HPV type detected (9.3%). 18.2% of women showed incident or progressive cytological abnormalities (7.8% ASC-US, 9.7% LSIL and 0.6% HSIL) and colposcopy revealed CIN2 (N = 2), CIN1 (N = 2) and VIN3 (N = 1). The preventable fraction of incident infections was 11.3%, 16.7%, and 35.2% for the 2v-4v-9v-HPV vaccines respectively (χ2 p < 0.0001). The overall burden of incident lesions attributable to the vaccine types were 9.1% for 2v-, 14.5% for 4v- and 30.9% for 9v-vaccine. High HPV incidence rates and high percentages of multiple HR-HPV infections were observed in a cohort of HIV-infected women receiving effective antiretroviral treatment. Primary prevention strategies based on the new 9v-HPV vaccine may help to prevent incident infections and disease progression in this cohort of women.

White matter damage, neuroinflammation, and neuronal integrity in HAND

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV­associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N­acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.