T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.

Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

A specific natural killer cells phenotypic signature associated to long term elite control of HIV infection.

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)-cells have recently gained much attention. We performed an in-deep phenotypic analysis of NK-cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty-seven PLWH (22 long-term EC [PLWH-long-term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH-onART], and 10 noncontrollers cART-naïve [PLWH-offART]), and 20 uninfected controls were included. NK-cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK-cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK-cells clusters based on the expression levels of the 15 different markers. PLWH-offART presented the highest disturbance of NK-cells homeostasis and this was not completely restored by long-term ART. Interestingly, long term spontaneous control of HIV (PLWH-LTEC group) was associated with a specific profile of NK-cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p-value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p-value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long-term control of HIV.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Discovery of circulating miRNAs as biomarkers of chronic Chagas heart disease via a small RNA-Seq approach.

Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies. Circulating microRNAs are increasingly reliable biomarkers of disease and therapeutic targets. To identify new circulating microRNAs for Chagas disease, we performed exploratory small RNA sequencing from the plasma of patients and performed de novo miRNA prediction, identifying potential new microRNAs. The levels of the new microRNAs temporarily named miR-Contig-1519 and miR-Contig-3244 and microRNAs that are biomarkers for nonchagasic cardiomyopathies, such as miR-148a-3p and miR-224-5p, were validated by quantitative reverse transcription. We found a specific circulating microRNA signature defined by low miR-Contig-3244, miR-Contig-1519, and miR-148a-3 levels but high miR-224-5p levels for patients with chronic Chagas disease. Finally, we predicted in silico that these altered circulating microRNAs could affect the expression of target genes involved in different cellular pathways and biological processes, which we will explore in the future.

Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals.

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87-15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

Diagnosis and Management of Adult Tuberculosis Patients Admitted to a Rural Hospital in Ethiopia.

Background  Ethiopia is one of the countries in the world with the highest rate of tuberculosis (TB). The aim of this study is to describe the characteristics of the patients with TB admitted to a rural hospital in Ethiopia in terms of both diagnosis and clinical management. Methods A retrospective descriptive observational study was conducted. Data were collected from patients older than 13 years who were admitted to the Gambo General Hospital for TB between May 2016 and September 2017. The variables studied were age, sex, symptoms, human immunodeficiency virus (HIV) serology, nutritional status, presence of anemia, chest x-ray or other complementary tests, type of diagnosis (smear microscopy, Xpert MTB-RIF (Cepheid, Sunnyvale, California, USA), or clinical diagnosis), treatment received, outcome, and days of admission. Results One hundred eighty-six patients, aged 13 years and older, were admitted to the TB unit. About 51.6% were female, and the median age was 35 years (interquartile range (IQR) 25-50). Cough was the most frequent symptom on admission (88.7%), and contact with a TB patient was only recognized by 22 patients (11.8%). HIV serology was performed in 148 patients (79.6%); seven were positive (4.7%). About 69.3% met the criteria for malnutrition (body mass index (BMI) <18.5). Most patients, 173 (93%), presented with pulmonary TB and were new cases (94.1%). Patients were diagnosed by clinical parameters in 75% of cases. Smear microscopy was performed in 148 patients, of which 46 (31.1%) were positive, and Xpert MTB-RIF results were only obtained in 16 patients, of which 6 (37.5%) were positive. Chest x-rays were performed in most patients (71%) and were suggestive of TB in 111 (84.1%). The average length of hospital stay was 32 days (confidence interval (CI) 13-50.5). Women tend to be younger than men, have more extrapulmonary TB, and were admitted longer. Nineteen patients died during admission (10.2%). Patients who die were more frequently malnourished (92.9% of those who die were malnourished compared to 67.1% of those who did not die, p = 0.036), tend to be admitted for a shorter time than the survivors and receive more concomitant antibiotic treatment. Conclusions In this rural Ethiopian setting, patients admitted to the hospital for TB are often malnourished (67.1%), the main presentation is pulmonary, mortality is one in 10 admissions and very often receive antibiotics in association with TB treatment (40%).

48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Silver Nanoparticles Produced by Laser Ablation and Re-Irradiation Are Effective Preventing Peri-Implantitis Multispecies Biofilm Formation.

Implant-associated infection due to biofilm formation is a growing problem. Given that silver nanoparticles (Ag-NPs) have shown antibacterial effects, our goal is to study their effect against multispecies biofilm involved in the development of peri-implantitis. To this purpose, Ag-NPs were synthesized by laser ablation in de-ionized water using two different lasers, leading to the production of colloidal suspensions. Subsequently, part of each suspension was subjected to irradiation one and three times with the same laser source with which it was obtained. Ag-NPs were immobilized on the surface of titanium discs and the resultant materials were compared with unmodified titanium coupons. Nanoparticles were physico-chemically analysed to determine their shape, crystallinity, chemical composition, and mean diameter. The materials were incubated for 90 min or 48 h, to evaluate bacterial adhesion or biofilm formation respectively with Staphylococcus aureus or oral mixed bacterial flora composed of Streptococcus oralis, Actinomyces naeslundii, Veionella dispar, and Porphyromonas gingivalis. Ag-NPs help prevent the formation of biofilms both by S. aureus and by mixed oral bacterial flora. Nanoparticles re-irradiated three times showed the biggest antimicrobial effects. Modifying dental implants in this way could prevent the development of peri-implantitis.

High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure.

Accumulation of mutations in epitopes of cytolytic-T-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ T-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50-100] and 57%[48-82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49-92] vs. 50%[33-75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Impact of Xpert MTB/RIF in the Diagnosis of Childhood Tuberculosis in Rural Ethiopia.

BACKGROUND: This study assesses the impact of the Xpert MTB/RIF in the diagnosis of childhood tuberculosis (TB) in a rural hospital in a resource-constrained setting. METHODS: Retrospective cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a defined protocol based on national guidelines. Samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory. RESULTS: Of the 201 children assessed for presumptive TB, 46.3% (93/201) were diagnosed with TB. Of these, 49.5% (46/93) were microbiologically confirmed, mostly by Xpert MTB/RIF (only one patient was diagnosed by smear alone). The rest were clinically diagnosed. Microbiologically confirmed patients had a higher mean age, longer duration of fever and cough and lymphadenopathy more frequently than those clinically diagnosed. Gastric aspirates were Xpert MTB/RIF-positive in 18.2% of the samples (26/143); none were smear-positive (0/140). Sputum samples were Xpert MTB/RIF-positive in 27.1% (13/35) of the samples and smear-positive in 8.6% (3/35). There were no HIV-positive patients and just one case of rifampicin-resistant TB. A long delay (median 15 days) was detected in returning the results. CONCLUSION: Xpert MTB/RIF serves as an important adjunctive test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the TB cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries such as Ethiopia still relies largely upon diagnostic algorithms and the clinician's skills.Lay summaryWorld Health Organization recommends the use of Xpert MTB/RIF to improve the microbiological diagnosis of childhood tuberculosis (TB) since 2014, but the impact of this test under real conditions in rural areas of low-income countries is not clear. We conducted a cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a clinical protocol based on national guidelines and samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory.Of the 201 children assessed, 46.3% (93/201) were diagnosed with tuberculosis. Of these, 48.4% (45/93) were microbiologically confirmed by Xpert MTB/RIF [smear microscopy only diagnosed the 5.4% (5/93)]. Patients with microbiologically confirmed tuberculosis had a higher mean age, longer duration of fever and cough and had lymphadenopathy more frequently than those clinically diagnosed. A long delay in returning the results (median 15 days) was detected. Xpert MTB/RIF serves as an important test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries still relies largely upon diagnostic algorithms and the clinician's skills.

Initiation of antiretroviral therapy in treatment-naive adults with HIV infection at the first specialist appointment.

BACKGROUND: Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence exists in our setting, where diagnosis and treatment are carried out in different contexts. METHODS: An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen. RESULTS: One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load (<50 copies/mL) at 48 weeks from starting ART. No serious adverse effects associated with the strategy were observed. In total, 101 participants continued care at 48 weeks with retention in HIV care rate of 93.5% (101/108). CONCLUSIONS: Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.

HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy.

The role of HCV on the HIV reservoir is controversial since the reduction on HIV-DNA levels after HCV eradication with IFNα/RBV treatment seems to be the result of drugs instead of HCV clearance. We assessed whether HCV eradication can decrease HIV-DNA content in HIV/HCV-coinfected patients treated with direct-acting antivirals, DAAs (IFNα/RBV-free regimens). Cell-associated HIV-DNA was measured by ddPCR in 25 HIV-monoinfected and 25 HIV/HCV-coinfected patients. There were no differences in HIV-DNA levels between groups neither at baseline nor at 12 weeks after DAAs treatment completion. Our results indicate that HCV does not appear to influence the HIV reservoir size and suggest the lack of an anti-HIV action for DAAs.

Epidemiologic and Economic Analysis of Rapid Antiretroviral Therapy Initiation with Bictegravir/Emtricitabine/Tenofovir Alafenamide in Spain.

OBJECTIVE: This study aimed to assess the potential epidemiological and economic impact of rapid initiation of human immunodeficiency virus (HIV) treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) on HIV transmission compared with the current initiation observed in clinical practice in Spain. METHODS: A transmission model was adapted to estimate the cumulative HIV infection incidence and potential cost savings based on the number of HIV infections prevented among men who have sex with men, heterosexual males and females, and people who inject drugs (PWID) over a 20-year time horizon. The analysis compared rapid antiretroviral therapy (ART) initiation with B/F/TAF (9 days from diagnosis until treatment initiation) versus current ART initiation practice (with an average of 35 days from diagnosis to treatment). People living with HIV were distributed according to their treatment status. Risk for transmission was assigned to undiagnosed, diagnosed in care and not receiving ART, and receiving ART but virally unsuppressed, which was estimated by sexual contact, needles and syringes shared among PWID, state of HIV infection, and ART use. RESULTS: In the base-case analysis, rapid ART initiation with B/F/TAF is expected to prevent 992 new HIV infections over the next 20 years compared with current ART initiation practices. Considering the lifetime costs of treating HIV infection, the reduction in HIV incidence could result in potential cost savings of €323 million. CONCLUSIONS: These results suggest that rapid ART initiation with B/F/TAF in newly diagnosed patients with HIV is a high-value strategy for the Spanish National Health System and society, reducing HIV incidence and thereby reducing future related direct and indirect costs of care.

Bone Deleterious Effects of Different NRTIs in Treatment-naïve HIV Patients After 12 and 48 Weeks of Treatment.

BACKGROUND: Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients. METHODS: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. RESULTS: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/µL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. CONCLUSION: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.

Increased risk factors associated with lower BMD in antiretroviral-therapy-naïve HIV-infected adult male.

BACKGROUND: Low BMD (bone mineral density) has been described as a non-AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy. METHODS: A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old who voluntary attended the Infectious Disease Division appointment in Hospital Fundación Jimenez Díaz in Madrid, from January 1st, 2014 to September 30th, 2017. All subjects underwent a baseline DXA scan (dual energy x-ray absorptiometry) performed prior to start antiretroviral treatment. Further, all patients who started treatment between May 1st and September 30th, 2017 were invited to participate in a substudy on bone mineral metabolism. All the information was collected through clinical history and complementary questionnaire. RESULTS: The mean age was 36.4 years, been 68% Caucasian, 29.3% Latin American and 2.7% African race. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/µL, IQR, 320-659). 10% had a count below 200 CD4 cells/µL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% were not engage in any regular exercise, 51.9% were active smokers and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the study participants. Low BMD (Z-score <- 2.0) was found in 22.8% of the patients. It was only observed a significant association of Z-score in lumbar spine (LS) with CD8 and the CD4/CD8 ratio, and with alcohol for femoral neck (FN) measurement. CONCLUSIONS: We find prevalence of increased bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if changes in actual guidelines are needed to assess BMD measurements in HIV-infected adult male patients under 50.

Progression Risk in People with HIV and COVID-19: Predictive Performance of Current Risk Scores.

People with HIV (PWH) might have a higher risk of adverse coronavirus disease 2019 (COVID-19) outcomes. Several scores were developed to predict COVID-19 progression to critical disease and are often used among PWH. We assessed the performance of two commonly used risk equations among PWH and COVID-19. Participants were identified from a multicenter cohort of 6,361 PWH on regular follow-up at 2 university hospitals. Of 99 HIV-infected individuals with confirmed SARS-CoV-2 infection, 63 had complete data and were included in this analysis. CALL and COVID-GRAM scores were calculated and participants were stratified into low-, intermediate-, and high-risk groups for each. Discrimination was assessed using receiver operating characteristic curves. Calibration was evaluated using observed versus expected (O:E) ratios and the Hosmer-Lemeshow χ2 goodness-of-fit statistic. Scores were adjusted by increasing one category level in individuals with nadir CD4 lymphocyte count <200/µL. Participants had a median nadir and current CD4 counts of 207 [interquartile range (IQR) 119-345] and 440 (IQR 280-719) cells/µL. Ten (15.9%) individuals progressed to critical disease and 4 (6.3%) died. Assessed scores showed acceptable discrimination (area under the curve 0.701-0.771) and were overall calibrated (O:E ratio 1.01). However, both overestimated the risk of progression among individuals in the low- and high-risk categories, whereas they underestimated the risk in the intermediate category (O:E 1.20-1.21). Thus, 50% of critically ill individuals were not identified as high risk. Assigning PWH with low nadir CD4 counts a higher risk of progression reduced the proportion of individuals not identified to 20%. COVID-19 risk scores had lower performance in PWH compared with that described in the general population and failed to adequately identify individuals who progressed to critical disease. Adjustment for nadir CD4 partially improved their accuracy. Risk equations incorporating HIV-related factors are needed.

Reasons for Choice of Antiretroviral Regimens in HIV Patients Presenting Late for Initial Treatment in Europe.

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count <200/µL and/or an AIDS-defining disease (late presenters, LPs), is still a challenge, even for HIV specialists. At present, there is little information on the decision process and selection criteria that physicians must take into account when choosing the presumably optimal initial ART for LPs. This study analyzes reasons for the individual choice of first-line ART in HIV LPs. We conducted a prospective multi-center study to analyze the decision-making process of physicians treating naive HIV patients presenting with a CD4 cell count <200/µL and/or an AIDS-defining condition. Two European HIV treatment centers based in Frankfurt (Germany) and A Coruna (Spain) participated in the study. Physicians documented the reasons that led to their decision for a specific first-line ART regimen. A questionnaire was designed for the study. Decisions of the participating physicians were evaluated. A total of 52 treatment decisions were analyzed. Evaluation of the choice of antiretroviral treatment demonstrated that for the overall group of physicians, simplicity of the regimen was the most important selection criterion in 34.6% of cases. The presence of comorbidities was given as the decisive selection criterion in 26.9%, followed by experience with the chosen drugs in 21.2% of cases. In the group of physicians choosing an integrase strand transfer inhibitor (INSTI)-based regimen for first-line ART, the same selection criteria were identified as in the overall group; 33.3% of clinicians selected an INSTI-based regimen because of its simplicity. The presence of comorbidities was the second most frequent decisive criterion (31.0%), followed by personal experience with the prescribed ART (23.8%). In the protease inhibitor group, simplicity was also the most common selection criterion with 40%. Results of clinical trials were stated as the most important criterion for the selection of ART in 38% of all cases, followed by the expected adherence of the patient (22%). Among the physicians who used a non-nucleoside reverse transcriptase inhibitor-based regimen, patients' desire to have children was the most frequent criterion for selection of ART (60%). An ongoing pregnancy was the second most frequent selection criterion, followed by ART's simplicity (8%). For patients treated with a single-tablet regimen, simplicity of ART was comprehensibly the most important decisive criterion (54.5%). Experience with the chosen drugs was the decisive selection criterion in 24.2%, followed by comorbidities in 18.2% of cases. Physicians' selection of individual ART in patients presenting late for first-line treatment seems to be predominantly dependent on patient-centered factors such as adherence issues as well as the clinical experience of physicians with the prescribed drugs.