Rapid expansion of lymphogranuloma venereum infections with fast diversification and spread of Chlamydia trachomatis L genovariants.

IMPORTANCE: Numerous international organizations, including the World Health Organization, have been drawing attention to the global increase in sexually transmitted infections. Twenty years ago, lymphogranuloma venereum (LGV) was mainly considered a tropical disease; in recent decades, however, LGV has been increasingly present in high-income countries. This increase has been linked to men who have sex with men who participate in highly interconnected sexual networks, leading to a rapid spread of LGV. This study focuses on the spread of LGV, presenting the largest time series of LGV prevalence in Spain, which includes more than a thousand diagnosed cases in one large city. The number of LGV cases diagnosed was analyzed over time, and a selection of strains was subjected to molecular genotyping. The results indicate that the LGV epidemic is gradually evolving toward an increasingly complex diversification due to the selection of successful genovariants that have emerged by mutation and recombination events, suggesting that we are moving toward an unpredictable scenario.

Monitoring monkeypox virus in saliva and air samples in Spain: a cross-sectional study.

BACKGROUND: The transmission of monkeypox virus occurs through direct contact, but transmission through saliva or exhaled droplets and aerosols has not yet been investigated. We aimed to assess the presence of monkeypox virus DNA and infectious virus in saliva samples and droplets and aerosols exhaled from patients infected with monkeypox virus. METHODS: We did a cross-sectional study in patients with monkeypox confirmed by PCR who attended two health centres in Madrid, Spain. For each patient, we collected samples of saliva, exhaled droplets within a mask, and aerosols captured by air filtration through newly developed nanofiber filters. We evaluated the presence of monkeypox virus in the samples by viral DNA detection by quantitative PCR (qPCR) and isolation of infectious viruses in cell cultures. FINDINGS: Between May 18 and July 15, 2022, 44 patients with symptomatic monkeypox attended two health centres in Madrid and were included in the study. All were cisgender men, with a median age of 35·0 years (IQR 11·3). We identified high loads of monkeypox virus DNA by qPCR in 35 (85%) of 41 saliva samples. Infectious monkeypox virus was recovered from 22 (67%) of 33 saliva samples positive for monkeypox virus DNA. We also found a significant association between the number of affected cutaneous areas or general symptoms and the viral load present in saliva samples. Droplets exhaled from patients with monkeypox, detected inside a mask, contained monkeypox virus DNA in 32 (71%) of 45 samples, with two of the 32 positive samples showing the presence of the infectious virus. Monkeypox virus DNA in aerosols, collected from the medical consultation room, were detected in 27 (64%) of 42 samples, despite patients wearing an FFP2 mask during the visit. Infectious virus was not recovered from aerosol samples. High levels of monkeypox virus DNA were identified in aerosols collected from a hospital isolation room housing a patient with monkeypox. INTERPRETATION: The identification of high viable monkeypox virus loads in saliva in most patients with monkeypox and the finding of monkeypox virus DNA in droplets and aerosols warrants further epidemiological studies to evaluate the potential relevance of the respiratory route of infection in the 2022 monkeypox virus outbreak. FUNDING: EU, Consejo Superior de Investigaciones Científicas, and Ciberinfec.

Elite controllers long-term non progressors present improved survival and slower disease progression.

Different phenotypes exhibiting no evidences of disease progression have been described in ART-naïve HIV-1 positive individuals. Long-term non progressors (LTNP) and elite controllers (EC) are low frequent examples of immunological and virological control in HIV-1 positive subjects, respectively. The combination of both phenotypes is even less frequent and studied despite being considered as models of HIV-1 functional cure. A multicenter, prospective study in retrospect including clinical and epidemiological data collected from 313 LTNP of 21 Spanish hospitals was carried out. LTNPs maintaining CD4+ T cell counts over 500 cells/µl and viral loads (VL) under 10,000 copies/mL for at least 10 years in the absence of antiretroviral therapy were followed for a median of 20.8 years (IQR = 15.6-25.5). A 52.1% were considered EC (undetectable VL) and LTNP (EC-LTNP) and a total of 171 (54.8%) and 42 (13.5%) out of the 313 participants maintained LTNP status for at least 20 and 30 years, respectively. EC-LTNP showed lower CD4+ T cell count loss (9.9 vs 24.2 cells/µl/year), higher CD4/CD8 ratio (0.01 vs - 0.09 in ratio), and lesser VL increase (no increase vs 197.2 copies/mL/year) compared with LTNPs with detectable VL (vLTNP). Survival probabilities for all-cause mortality at 30 years from HIV + diagnosis were 0.90 for EC-LTNP and 0.70 for vLTNP (p = 2.0 × 10-3), and EC-LTNP phenotype was the only factor associated with better survival in multivariate analyses (HR = 0.28; 95% CI 0.10-0.79). The probability to preserve LTNP status at 30 years was 0.51 for EC-LTNP and 0.18 for vLTNP (p < 2.2 × 10-16). Risk factors associated to the loss of LTNP status was: higher age at diagnosis and the increase of VL, whereas the increase of CD4+ T cell counts and CD4/CD8 ratio, the initial EC-LTNP phenotype and HCV coinfection were protective factors. EC-LTNP phenotype was associated with improved survival and slower disease progression compared with other phenotypes of LTNP. EC-LTNP individuals represent one of the most favorable phenotypes of immune activation against HIV-1 found in nature and, therefore, are strong candidates to be considered a model of functional cure of HIV-1 infection.

Monkeypox outbreak in Madrid (Spain): Clinical and virological aspects.

BACKGROUND: Monkeypox is the most prevalent Orthopoxvirus zoonosis infection since the eradication of smallpox. The current multi-country outbreak involves five WHO regions affecting mainly Europe. Accurate clinical and virological aspects of the disease outside endemic areas are needed. METHODS: We performed an observational study of cases diagnosed in Madrid (Spain) (May/June 2022). Confirmation from vesicular lesions swabs, Orthopoxvirus real-time PCR, sequencing, phylogenetic analysis, and direct detection by Electron microscopy was performed. In addition, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data from all confirmed cases. FINDINGS: We extracted data from 48 patients, all cisgender men. The median age was 35 years (IQR 29 - 44), and 87.5% were MSM. The most prevalent symptoms were the presence of vesicular-umbilicated and pseudo-pustular skin lesions (93.8%), asthenia (66.6%), and fever (52.1%). In addition, the location of the lesions in the genital or perianal area was related to the role in sexual intercourse (p<0.001). Sequencing analysis indicated the virus circulating in Spain belongs to the western African clade. Like the other European cases in the outbreak, the Spanish isolates are a direct descendant of viruses previously detected in Nigeria, the UK, Singapore, and Israel in 2017-2018. CONCLUSIONS: Monkeypox is an emerging infectious disease in Europe where community transmission is reported, mainly in MSM. The first symptom was skin lesions instead of classical fever and rash. The disease follows a self-limited course, and there have been no cases with a serious presentation or severe complications.

Immunoescape of HIV-1 in Env-EL9 CD8 + T cell response restricted by HLA-B*14:02 in a Non progressor who lost twenty-seven years of HIV-1 control.

BACKGROUND: Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers, have been associated with effective immunodominant HIV-1 Gag-CD8 + T-cell responses restricted by protective HLA-B alleles. Individuals carrying HLA-B*14:02 control HIV-1 infection is related to an immunodominant Env-CD8 + T-cell response. Limited data are available on the contribution of HLA-B*14:02 CD8 + T -cells in LTNPs. RESULTS: In this study, we performed a virological and immunological detailed analysis of an HLA-B*14:02 LNTP individual that lost viral control (LVC) 27 years after HIV-1 diagnosis. We analysed viral evolution and immune escape in HLA-B*14:02 restricted CD8 + T -cell epitopes and identified viral evolution at the Env-EL9 epitope selecting the L592R mutation. By IFN-γ ELISpot and immune phenotype, we characterized HLA- B*14:02 HIV-1 CD8 + T cell responses targeting, Gag-DA9 and Env-EL9 epitopes before and after LVC. We observed an immunodominant response against the Env-EL9 epitope and a decreased of the CD8 T + cell response over time with LVC. Loss of Env-EL9 responses was concomitant with selecting K588R + L592R mutations at Env-EL9. Finally, we evaluated the impact of Env-EL9 escape mutations on HIV-1 infectivity and Env protein structure. The K588R + L592R escape variant was directly related to HIV-1 increase replicative capacity and stability of Env at the LVC. CONCLUSIONS: These findings support the contribution of immunodominant Env-EL9 CD8 + T-cell responses and the imposition of immune escape variants with higher replicative capacity associated with LVC in this LNTP. These data highlight the importance of Env-EL9 specific-CD8 + T-cell responses restricted by the HLA-B*14:02 and brings new insights into understanding long-term HIV-1 control mediated by Env mediated CD8 + T-cell responses.

Identification of CRF66_BF, a New HIV-1 Circulating Recombinant Form of South American Origin.

Circulating recombinant forms (CRFs) are important components of the HIV-1 pandemic. Among 110 reported in the literature, 17 are BF1 intersubtype recombinant, most of which are of South American origin. Among these, all 5 identified in the Southern Cone and neighboring countries, except Brazil, derive from a common recombinant ancestor related to CRF12_BF, which circulates widely in Argentina, as deduced from coincident breakpoints and clustering in phylogenetic trees. In a HIV-1 molecular epidemiological study in Spain, we identified a phylogenetic cluster of 20 samples from 3 separate regions which were of F1 subsubtype, related to the Brazilian strain, in protease-reverse transcriptase (Pr-RT) and of subtype B in integrase. Remarkably, 14 individuals from this cluster (designated BF9) were Paraguayans and only 4 were native Spaniards. HIV-1 transmission was predominantly heterosexual, except for a subcluster of 6 individuals, 5 of which were men who have sex with men. Ten additional database sequences, from Argentina (n = 4), Spain (n = 3), Paraguay (n = 1), Brazil (n = 1), and Italy (n = 1), branched within the BF9 cluster. To determine whether it represents a new CRF, near full-length genome (NFLG) sequences were obtained for 6 viruses from 3 Spanish regions. Bootscan analyses showed a coincident BF1 recombinant structure, with 5 breakpoints, located in p17 gag , integrase, gp120, gp41-rev overlap, and nef, which was identical to that of two BF1 recombinant viruses from Paraguay previously sequenced in NFLGs. Interestingly, none of the breakpoints coincided with those of CRF12_BF. In a maximum likelihood phylogenetic tree, all 8 NFLG sequences grouped in a strongly supported clade segregating from previously identified CRFs and from the CRF12_BF "family" clade. These results allow us to identify a new HIV-1 CRF, designated CRF66_BF. Through a Bayesian coalescent analysis, the most recent common ancestor of CRF66_BF was estimated around 1984 in South America, either in Paraguay or Argentina. Among Pr-RT sequences obtained by us from HIV-1-infected Paraguayans living in Spain, 14 (20.9%) of 67 were of CRF66_BF, suggesting that CRF66_BF may be one of the major HIV-1 genetic forms circulating in Paraguay. CRF66_BF is the first reported non-Brazilian South American HIV-1 CRF_BF unrelated to CRF12_BF.

Comparison of Polydrug Use Prevalences and Typologies between Men Who Have Sex with Men and General Population Men, in Madrid and Barcelona.

This study compares the prevalence of drug use and the typologies of polydrug use (PDU) in men who have sex with men (MSM) and general population men (GPM). Participants were men aged 16-64, living in the provinces of Madrid and Barcelona: 1720 were recruited in a GPM survey, and 2658 were HIV-negative MSM from HIV/STIs diagnosis services. Lifetime and last-year prevalence of drug use and prevalence ratios (PRs) of MSM to GPM for the different drugs were calculated using Poisson regression. Latent class analysis (LCA) was performed to identify typologies of PDU. Lifetime use of the drugs considered was higher in MSM, and even higher for drug use in the last-year: PRs for cannabis, hallucinogens and cocaine ranged from 2-5; for amphetamine, ecstasy and methamphetamine 12-16; and above 60 for ketamine, GHB/GBL, inhalants and mephedrone. In the LCA for lifetime PDU four classes arose from the GPM (No-PDU (79.6%); Conventional PDU (13.8%); Intensive conventional PDU (4.9%); Heavy PDU (1.8%)) and four among MSM (No-PDU (57.7%); Conventional PDU plus poppers (18.8%); PDU preferring chemsex drugs (6.4%); Heavy PDU (17.2%)). For PDU during the last-year, three classes arose in the GPM: No-PDU (94.7%); Conventional PDU (4.3%); Heavy PDU (0.9%). For MSM, we identified four classes: No-PDU (64.7%); Conventional PDU plus poppers (15.6%); PDU preferring chemsex drugs (6.2%); Heavy PDU (13.5%). MSM should be considered a priority group for the prevention of the use of all drugs but the heterogeneity of PDU typologies regarding users' preference towards conventional and/or sexualised drugs needs to be taken into account.

Sexualized drug injection among men who have sex with men in Madrid and Barcelona as the first episode of drug injecting.

BACKGROUND: We estimate the prevalence of drug injection, the variables associated with having ever injected and the proportion of ever injectors whose first drug injection was for having sex; we describe the first drug injection episode, analyze the drugs most frequently injected and estimate the prevalence of risky injecting behaviors. METHODS: The participants were 3387 MSM without a previous HIV diagnosis attending four HIV/STI diagnosis services in Madrid and Barcelona. Lifetime prevalence and prevalence ratios (PRs) by different factors were calculated using Poisson regression models with robust variance. We compared the characteristics of first drug injection episode, lifetime injection and risky injecting behaviors of those whose first injection was for sex (FIS) with those whose was not (non-FIS). RESULTS: Lifetime prevalence of injection was 2.1% (CI 1.7-2.7). In the multivariate analysis, it was strongly associated with having been penetrated by more than five men in the last 12 months (aPR = 10.4; CI 2.5-43.4) and having met most of their partners at private parties (aPR = 7.5; CI 4.5-12.3), and less strongly with other factors. Of those who had ever injected drugs, 81.9% injected for sex the first time they injected drugs (FIS). At first injection, FIS participants had a mean age of 31 years, 62.7% used mephedrone and 32.2% methamphetamine on that occasion. Of this FIS group 39.0% had ever shared drugs or equipment and 82.6% had always shared for sex. Some 30.8% of non-FIS reported having also injected drugs for sex later on. CONCLUSIONS: Only two out of a hundred had ever injected, most to have sex and with frequent drug or injecting equipment sharing. Injecting for sex is the most common first episode of drug injection and is the most efficient risky behavior for the transmission of HIV, hepatitis B or C and other blood-borne infections. MSM participating in private parties should be considered a priority group for prevention policies.

Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort.

OBJECTIVES: We aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and factors associated with seropositivity and asymptomatic coronavirus disease 2019 (COVID-19) among people with HIV (PWH). METHODS: This was a cross-sectional study carried out within the cohort of the Spanish HIV Research Network. Participants were consecutive PWH with plasma collected from 1st April to 30th September 2020. We determined SARS-CoV-2 antibodies (Abs) in plasma. Illness severity (NIH criteria) was assessed by a review of medical records and, if needed, participant interviews. Multivariable logistic regression analysis was used to identify predictors of seropositivity among the following variables: sex, age, country of birth, education level, comorbidities (hypertension, chronic heart disease, diabetes mellitus, non-AIDS-related cancer, chronic kidney disease, cirrhosis), route of HIV acquisition, prior AIDS, CD4+ cell count, HIV viral load, nucleoside/nucleotide reverse transcriptase inhibitor (N [t]RTI) backbone, type of third antiretroviral drug, and month of sample collection. RESULTS: Of 1076 PWH (88.0% males, median age 43 years, 97.7% on antiretroviral therapy, median CD4+ 688 cells/mm3, 91.4% undetectable HIV viral load), SARS-CoV-2 Abs were detected in 91 PWH, a seroprevalence of 8.5% (95%CI 6.9-10.3%). Forty-five infections (45.0%) were asymptomatic. Variables independently associated with SARS-CoV-2 seropositivity were birth in Latin American countries versus Spain (adjusted odds ratio (aOR) 2.30, 95%CI 1.41-3.76, p 0.001), and therapy with tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) versus tenofovir alafenamide (TAF)/FTC as the N(t)RTI backbone (aOR 0.49, 95%CI 0.26-0.94, p 0.031). CONCLUSIONS: Many SARS-CoV-2 infections among PWH were asymptomatic, and birth in Latin American countries increased the risk of SARS-CoV-2 seropositivity. Our analysis, adjusted by comorbidities and other variables, suggests that TDF/FTC may prevent SARS-CoV-2 infection among PWH.

Identification of CRF89_BF, a new member of an HIV-1 circulating BF intersubtype recombinant form family widely spread in South America.

Circulating recombinant forms (CRFs) contribute substantially to the HIV-1 pandemic. Among 105 CRFs described in the literature, 16 are BF intersubtype recombinants, most of South American origin, of which CRF12_BF is the most widely spread. A BF recombinant cluster identified in Bolivia was suggested to represent a new CRF_BF. Here we find that it belongs to a larger cluster incorporating 39 viruses collected in 7 countries from 3 continents, 22 of them in Spain, most from Bolivian or Peruvian individuals, and 12 in South America (Bolivia, Argentina, and Peru). This BF cluster comprises three major subclusters, two associated with Bolivian and one with Peruvian individuals. Near full-length genome sequence analyses of nine viruses, collected in Spain, Bolivia, and Peru, revealed coincident BF mosaic structures, with 13 breakpoints, 6 and 7 of which coincided with CRF12_BF and CRF17_BF, respectively. In a phylogenetic tree, they grouped in a clade closely related to these CRFs, and more distantly to CRF38_BF and CRF44_BF, all circulating in South America. These results allowed to identify a new HIV-1 CRF, designated CRF89_BF. Through phylodynamic analyses, CRF89_BF emergence was estimated in Bolivia around 1986. CRF89_BF is the fifth CRF member of the HIV-1 recombinant family related to CRF12_BF.

DBP rs7041 and DHCR7 rs3829251 are Linked to CD4+ Recovery in HIV Patients on Antiretroviral Therapy.

Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+. Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study. Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015). Conclusion: In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts.

Preventive Efficacy of Tenofovir/Emtricitabine Against Severe Acute Respiratory Syndrome Coronavirus 2 Among Pre-Exposure Prophylaxis Users.

BACKGROUND: The preventive effect that tenofovir/emtricitabine (FTC) could have against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human immunodeficiency virus-negative people is unknown. The objective of this study was to analyze the seroprevalence and clinical manifestations of COVID-19 among users of pre-exposure prophylaxis (PrEP), disoproxil fumarate/FTC (TDF/FTC), or tenofovir alafenamide (TAF)/FTC and to compare it to that of a control group. METHODS: An observational descriptive study of the seroprevalence of antibodies for SARS-CoV-2 among men who have sex with men and transgender women without use of PrEP (Group 1; n = 250) and PrEP users with TDF/FTC (n = 409) or TAF/FTC (n = 91) (Group 2; n = 500) was conducted from May11, 2020 to June 27, 2020. All participants were provided with a structured questionnaire that collected information on the variables to be analyzed, and testing for immunoglobulin G antibodies to SARS-CoV-2 (chemiluminescent microparticle immunoassay) was then carried out. RESULTS: The seroprevalence of SARS-CoV-2 was 9.2% (95% confidence interval [CI], 5.9-13.5) in the group without PrEP and 15.0% (95% CI, 12.0-18.4) in the group with PrEP (P = .026). Among users of TDF/FTC it was 14.7% (95% CI, 11.4-18.5), and in users of TAF/FTC it was 16.5% (95% CI, 9.5-25.7) (P = .661). In those who tested positive for SARS-CoV-2 and receiving PrEP, 57.4% manifested symptoms, compared with 78.3% in the control group (P = .070). In users of TDF/FTC the figure was 53.3% and in users of TAF/FTC the figure was 73.3% (P = .100). The duration of symptoms was 11.5 days in the control group, 9.0 days in PrEP users (P = .116), 7.0 days in users of TDF/FTC, and 13.0 days in users of TAF/FTC (P = .100). CONCLUSIONS: Users of PrEP, TDF/FTC, or TAF/FTC presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in relation to clinical manifestations. The PrEP users should use the same prevention measures as those indicated for the general population.

Persistent HIV-controllers are more prone to spontaneously clear HCV: a retrospective cohort study.

INTRODUCTION: HIV-controllers have the ability to spontaneously maintain viraemia at low or undetectable levels in the absence of antiretroviral treatment. Furthermore, HIV-controllers seem to have a superior capacity to spontaneously clear hepatitis C virus (HCV) compared to non HIV-controllers. Some of these subjects eventually lose HIV-controller status (transient controllers), whereas some HIV-controllers show a persistent natural HIV control (persistent controllers). We aimed to analyse whether persistent controllers have superior capacity to spontaneously clear HCV compared to transient controllers. METHODS: We recruited HIV-controllers from January 1981 up to October 2016 with available antibodies to HCV (anti-HCV) data (n = 744). Factors associated with HIV spontaneous control in relation to HCV status were analysed in persistent and transient HIV-controllers with anti-HCV positive (n = 202 and n = 138 respectively) in comparison with 1700 HCV positive non HIV-controllers recruited from January 1981 up to March 2018, bivariate and multivariate analyses, following a logistic regression model, were applied. In addition, the factors related to the loss and time to lose HIV-controller status were explored (n = 744) using Log rank test and Kaplan-Meier curves, in this case the multivariate analysis consisted in a Cox regression model. RESULTS: A higher frequency of HCV spontaneous clearance was found in persistent HIV-controllers (25.5%) compared to non-controllers (10.2%). After adjusting for potential confounders, as sex, age, HIV transmission risk, CD4+ T-cell nadir and time of follow-up, HCV clearance was independently associated with persistent HIV spontaneous control (p = 0.002; OR (95% CI) = 2.573 (1.428 to 4.633)), but not with transient spontaneous control (p = 0.119; 1.589 (0.888 to 2.845)). Furthermore, persistent HIV-controllers were more likely to spontaneously clear the HCV in comparison with transient controllers (p = 0.027; 0.377 (0.159 to 0.893). Finally, not to lose or lengthen the time of losing this control was independently associated with HCV spontaneous clearance (p = 0.010; 0.503 (0.297 to 0.850). CONCLUSIONS: This study shows an association between spontaneous persistent HIV-control and HCV spontaneous clearance. The study findings support the idea of preserved immune mechanisms in persistent HIV control implicated in HCV spontaneous clearance. These results highlight persistent HIV-controllers but not transient controllers as a good model of functional HIV cure.

Health care issues affecting transgender people living with HIV: an opportunity for improvement.

The high vulnerability of transgender (TG) persons to HIV infection and the difficulties associated with access to health services can lead to delays in the diagnosis and treatment of HIV infection, thus increasing the risk of transmission of HIV by this population. We performed a retrospective study to analyze the main characteristics of TG living with HIV infection in a hospital in Madrid, Spain and to identify issues related to lack of access to the health care system and combination antiretroviral therapy (cART). We analyzed 28 TG, of whom 22 (78.6%) were TG women. Median age was 28 years (interquartile range [IQR]: 29-45), 24 (85.7%) were Latin American (all of them without health insurance), and 12 (42.8%) were sex workers. Accessibility to the health system was more difficult for 22 (78.6%) of foreign-born TG people living with HIV, with a median delay to initiation of cART of six months (IQR: 2-24). These values were greater than those recorded for the control group comprising other people living with HIV (16.9% and one month, respectively). At the first access to health care in our hospital, CD4+ cell count and HIV viral load (VL) were worse in TG patients, with a median baseline CD4+ cell count below 350 cells/µl and a higher median HIV VL, both in naïve patients (28.6%) and in pre-treated patients whose therapy was interrupted owing to access-related issues (46.4%). These data show high vulnerability to HIV infection among TG and highlight that issues associated with access to health care can cause delays in the diagnosis and treatment of HIV infection. Based on our results, we think that the health care system should adapt to the sociodemographic, clinical, and behavioral characteristics of TG people living with HIV and develop specific, targeted preventive programs to address the vulnerability of this group.

High-Risk Sexual Practices Contribute to HIV-1 Double Infection Among Men Who Have Sex with Men in Madrid.

Data on the prevalence of double infection (DI) in HIV individuals are lacking in Spain. To fill this gap, we analyzed the prevalence of DI in a cohort of men who have sex with men (MSM) and examined factors contributing to DI. We selected 81 MSM attending Centro Sanitario Sandoval, a sexually transmitted diseases clinic in Madrid. We obtained by ultra-deep sequencing the proviral sequences in gag and env genes and performed a phylogenetic analysis for the identification of DI. Clinical, behavioral, host, and viral factors were studied for its association with DI. We detected six individuals with DI and one case of superinfection with a global prevalence of 8.6%. The genetic distance among the subtype B viruses in monoinfected individuals (24.4%) was lower than the distance between the two viruses in subtype B DI individuals (29.5%). Individuals with a high number of sexual contacts (>25 partners/year) had an 8.66 times higher risk of DI (p = .017). In this MSM cohort the prevalence of HIV DI was estimated at 8.6%. DI was strongly associated with the number of sexual partners. Because of the pathogenic consequences of HIV DI, this high prevalence should promote public health programs targeted at high-risk population such as MSM for the control of HIV infection and DI. HIV DI should be considered for a better clinical management of these individuals.

Psychological distress in women and men living with HIV in Spain: a cross-sectional telephone survey.

BACKGROUND: Psychological distress includes a broader range of experiences, varying from less severe symptoms of depression and anxiety to severe psychiatric disease. Global estimates for depression and anxiety in 2017 were 3.4% and 3.8%, respectively. While for people living with HIV, global estimates were 16% and 33%, respectively. OBJECTIVE: We aimed to determine the prevalence of psychological distress by gender and associated characteristics in patients living with HIV. METHODS: A cross-sectional study was conducted within the Spanish HIV Research Network CoRIS. Participants were interviewed by telephone between 2010 and 2014 about their psychological distress, sociodemographics, drug consumption, self-perceived health and combined antiretroviral therapy (cART) adherence. Laboratory tests and medical history details were collected from CoRIS. Logistic regression was used to identify characteristics associated with psychological distress. FINDINGS: We interviewed 99 women and 464 men, both living with HIV. A greater proportion of women (51, 51.5%) reported psychological distress than men (179, 38.6%; p<0.01). Non-adherence to cART (OR 4.6 and 2.3, 95% CI 1.4‒15.1 and 1.3‒4.2) and non-use of cART (8.4 and 1.8, 2.2‒32.4 and 1.1‒2.8) were related to psychological distress in women and men, respectively. Spending little time in leisure-based physical activity was related to psychological distress in women (3.1, 1.1‒9.0). Living alone (2.0, 1.3‒3.0) and being unemployed (2.3, 1.4‒3.6) were related to psychological distress in men. CONCLUSIONS AND CLINICAL IMPLICATIONS: As people living with HIV have a high prevalence of psychological distress, their regular screening appointments should include psychological assessment. A gendered approach is needed to detect and manage psychological distress.

Soluble PD-L1: a potential immune marker for HIV-1 infection and virological failure.

Despite viral control, basal chronic inflammation and its related comorbidities remain unsolved problems among HIV-infected individuals. Soluble factors derived from myeloid cells have emerged as potent markers associated with HIV-related comorbidities and mortality. In the present report, we explored the relationship between soluble programmed death-ligand 1 (sPD-L1) and HIV-1 infection, antiretroviral therapy (ART), CD4/CD8 ratio, viral load (VL), and sexually transmitted coinfections.A prospective observational study on 49 HIV-1 infected adults.We found sPD-L1 levels were significantly higher in 49 HIV infected subjects than in 30 uninfected adults (1.05 ng/ml vs 0.52 ng/ml; P < .001). In this line, sPD-L1 levels were found to be elevated in 16 HIV infected subjects with undetectable VL compared with the uninfected subjects (0.75 ng/ml vs 0.52 ng/ml; P = .02). Thirteen ART-treated individuals with virological failure exhibited the highest sPDL1 levels, which were significantly higher than both 20 ART naïve infected individuals (1.68 ng/ml vs 0.87 ng/ml; P = .003) and the 16 ART-treated individuals with suppressed viremia (1.68 ng/ml vs 0.79 ng/ml; P = 002). Entire cohort data showed a statistically significant positive correlation between VL and sPD-L1 levels in plasma (r = 0.3; P = 036).Our findings reveal sPDL-1 as a potential biomarker for HIV infection especially interesting in those individuals with virological failure.

Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure.

Elite controllers (EC) represent a small subset of HIV-1-infected people that spontaneously control viral replication. However, natural virological suppression and absence of immune dysfunction are not always long-term sustained. We define exceptional EC (EEC) as HIV-1 subjects who maintain the EC characteristics without disease progression for more than 25 years. We analyzed three EEC, diagnosed between 1988 and 1992, who never showed signs of clinical disease progression in absence of any antiretroviral treatment. A comprehensive clinical, virological, and immunological study was performed. The individuals simultaneously exhibited ≥3 described host protective alleles, low levels of total HIV-1 DNA (<20 copies/106 CD4+ T-cells) without evidence of replication-competent viruses (<0.025 IUPM), consistent with high levels of defective genomes, strong cellular HIV-1-specific immune response, and a high poly-functionality index (>0.50). Inflammation levels of EEC were similar to HIV-1 negative donors. Remarkably, they showed an exceptional lack of viral evolution and 8-fold lower genetic diversity (<0.01 s/n) in env gene than other EC. We postulate that these EEC represent cases of spontaneous functional HIV-1 cure. A non-functional and non-genetically evolving viral reservoir along with an HIV-1-specific immune response seems to be key for the spontaneous functional cure.

Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial.

BACKGROUND: Penicillin G Benzathine (PGB) is the cornerstone of syphilis treatment. However, its intramuscular (IM) administration is associated with pain at the site of injection. The dilution of PGB with local anesthetics is recommended in some guidelines, but the evidence that supports it, particularly in adults and in HIV infection, is scarce. Preliminary clinical experience also suggests that the IM administration of PGB through increased needle gauges might improve its tolerability. The aim of the study to identify less painful ways of administering IM PGB in the treatment of syphilis in adults. METHODS: Multicenter, randomized, double-blinded clinical trial in patients diagnosed with primary syphilis that required a single IM injection of PGB 2400,00 IU. Patients were randomized to receive PGB diluted with 0.5 mL mepivacaine 1% (MV) or PGB alone, and both groups either with a long 19G or short 21G IM needle. The primary objective was the effect on local pain immediately after the administration through a visual scale questionnaire on pain (0 to 10). RESULTS: One hundred eight patients were included, 27 in each group. Ninety-four (94.4%) were male, and 41.7% were also HIV-infected. Mean age 36.6 years (SD 11). Significant differences in immediate pain intensity were observed when comparing the long 19G group with anesthesia (mean pain intensity, [MPI] 2.92 [CI 95% 1.08-4.07]) vs long 19G without anesthesia (MPI 5.56 [CI 95% 4.39-6.73), p < 0.001; and also between short 21G group with anesthesia (MPI 3.36 [CI 95% 2.22-4.50]) vs short 21G without anesthesia (MPI 5.06 [CI 95% 3.93-6.19]), p = 0.015). No significant differences in immediate pain were observed between 19G and 21G in the presence or absence of anesthesia (p = 1.0 in both cases). No differences were found between study arms after 6 and 24 h. CONCLUSIONS: The IM administration of 1% mepivacaine-diluted PGB induces significantly less immediate local pain as compared to PGB alone. The needle gauge did not have any effect on the pain. Based on these results, we suggest anesthetic-diluted IM PGB as the standard treatment for primary syphilis. TRIAL REGISTRATION: EudraCT 2014-003969-24 (Date of registration 18/09/2014).