Should We Expect an Increase in the Number of Cancer Cases in People with Long COVID?

The relationship between viral infections and the risk of developing cancer is well known. Multiple mechanisms participate in and determine this process. The COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in the deaths of millions of people worldwide. Although the effects of COVID-19 are limited for most people, a large number of people continue to show symptoms for a long period of time (long COVID). Several studies have suggested that cancer could also be a potential long-term complication of the virus; however, the causes of this risk are not yet well understood. In this review, we investigated arguments that could support or reject this possibility.

Identifying the needs of older people living with HIV (≥ 50 years old) from multiple centres over the world: a descriptive analysis.

BACKGROUND: Older People Living with HIV (OPWH) combine both aging and HIV-infection features, resulting in ageism, stigma, social isolation, and low quality of life. This context brings up new challenges for healthcare professionals, who now must aid patients with a significant comorbidity burden and polypharmacy treatments. OPWH opinion on their health management is hardly ever considered as a variable to study, though it would help to understand their needs on dissimilar settings. METHODS: We performed a cross-sectional, comparative study including patients living with HIV aged ≥50 years old from multiple centers worldwide and gave them a survey addressing their perception on overall health issues, psychological problems, social activities, geriatric conditions, and opinions on healthcare. Data was analyzed through Chisquared tests sorting by geographical regions, age groups, or both. RESULTS: We organized 680 participants data by location (Center and South America [CSA], Western Europe [WE], Africa, Eastern Europe and Israel [EEI]) and by age groups (50- 55, 56-65, 66-75, >75). In EEI, HIV serostatus socializing and reaching undetectable viral load were the main problems. CSA participants are the least satisfied regarding their healthcare, and a great part of them are not retired. Africans show the best health perception, have financial problems, and fancy their HIV doctors. WE is the most developed region studied and their participants report the best scores. Moreover, older age groups tend to live alone, have a lower perception of psychological problems, and reduced social life. CONCLUSIONS: Patients' opinions outline region- and age-specific unmet needs. In EEI, socializing HIV and reaching undetectable viral load were the main concerns. CSA low satisfaction outcomes might reflect high expectations or profound inequities in the region. African participants results mirror a system where general health is hard to achieve, but HIV clinics are much more appealing to them. WE is the most satisfied region about their healthcare. In this context, age-specific information, education and counseling programs (i.e. Patient Reported Outcomes, Patient Centered Care, multidisciplinary teams) are needed to promote physical and mental health among older adults living with HIV/AIDS. This is crucial for improving health-related quality of life and patient's satisfaction.

Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy.

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes in the environment. These fluctuations are controlled by a very complex molecular mechanism, the circadian clock, that regulates the expression of multiple genes to ensure the right functioning of the body. An individual's circadian system is altered during aging, and this is related to numerous age-associated pathologies and other alterations that could contribute to the development of cancer. Nowadays, there is an increasing interest in understanding how circadian rhythms could be used in the treatment of cancer. Chronotherapy aims to understand the impact that biological rhythms have on the response to a therapy to optimize its action, maximize health benefits and minimize possible adverse effects. Clinical trials so far have confirmed that optimal timing of treatment with chemo or immunotherapies could decrease drug toxicity and increase efficacy. Instead, chronoradiotherapy seems to minimize treatment-related symptoms rather than tumor progression or patient survival. In addition, potential therapeutic targets within the molecular clock have also been identified. Therefore, results of the application of chronotherapy in cancer therapy until now are challenging, feasible, and could be applied to clinical practice to improve cancer treatment without additional costs. However, different limitations and variables such as age, sex, or chronotypes, among others, should be overcome before chronotherapy can really be put into clinical practice.

Senotherapeutics in Cancer and HIV.

Cellular senescence is a stress-response mechanism that contributes to homeostasis maintenance, playing a beneficial role during embryogenesis and in normal adult organisms. In contrast, chronic senescence activation may be responsible for other events such as age-related disorders, HIV and cancer development. Cellular senescence activation can be triggered by different insults. Regardless of the inducer, there are several phenotypes generally shared among senescent cells: cell division arrest, an aberrant shape, increased size, high granularity because of increased numbers of lysosomes and vacuoles, apoptosis resistance, defective metabolism and some chromatin alterations. Senescent cells constitute an important area for research due to their contributions to the pathogenesis of different diseases such as frailty, sarcopenia and aging-related diseases, including cancer and HIV infection, which show an accelerated aging. Hence, a new pharmacological category of treatments called senotherapeutics is under development. This group includes senolytic drugs that selectively attack senescent cells and senostatic drugs that suppress SASP factor delivery, inhibiting senescent cell development. These new drugs can have positive therapeutic effects on aging-related disorders and act in cancer as antitumor drugs, avoiding the undesired effects of senescent cells such as those from SASP. Here, we review senotherapeutics and how they might affect cancer and HIV disease, two very different aging-related diseases, and review some compounds acting as senolytics in clinical trials.

Elevated levels of serum CDCP1 in individuals recovering from severe COVID-19 disease.

BACKGROUND: COVID-19 survivors report residual lung abnormalities after discharge from the hospital. The aim of this study was to identify biomarkers in serum and induced sputum samples from patients after hospitalization for COVID-19. METHODS: Patients admitted to hospitals in Spain with laboratory-confirmed COVID-19 were recruited for this study. SARS-CoV-2-infected patients were divided into groups with mild/moderate and severe disease according to the severity of their symptoms during hospitalization. Levels of 92 biomarkers were measured in serum and induced sputum samples. RESULTS: A total of 108 patients (46.2% severe cases) were included in this study. The median number of days after the onset of symptoms was 104. A significant difference was observed in diffusing capacity for carbon monoxide (DLCO), an indicator of lung function, whereby DLCO <80% was significantly lower in severe cases (p <0.001). Differences in inflammatory biomarkers were observed between patients with mild/moderate and severe disease. For some biomarkers, correlations in serum and induced sputum levels were detected. Independent predictors of severe disease were DLCO <80% and the serum CDCP1 value. CONCLUSIONS: Higher levels of CDCP1 remain after hospital discharge and are associated with the severity of COVID-19. The possible prognostic implications warrant further investigation.

Deprescribing of non-antiretroviral therapy in HIV-infected patients.

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Gender differences for frailty in HIV-infected patients on stable antiretroviral therapy and with an undetectable viral load.

BACKGROUND: Patients with HIV infection suffer from accelerated aging. In this context, frailty could be a relevant problem that aggravates the quality of life (QoL) and morbi-mortality of these patients. Our objective was to determine the prevalence of frailty and pre-frailty in HIV-infected patients in our cohort as well as their risk factors and QoL. METHODS: This was a prospective cross-sectional study of HIV-infected people aged ≥18 years on a stable antiretroviral regimen (ART) ≥1 year. Frailty was defined by ≥3 of 5 Fried's criteria: weight loss, low physical activity, exhaustion, weak grip strength and slow walking time. Variables related to sociodemographics, HIV infection, comorbidities, polypharmacy, and QoL were evaluated. Independent predictors of frailty were evaluated using collinearity in a multivariate logistic regression analyses (backward stepwise elimination). RESULTS: The 248 people studied has a mean age of 49 years, 63.7% were male, and 81% were Caucasian. The prevalence of pre-frailty and fragility was 39.1% and 4.4%, respectively. The main route of HIV acquisition was heterosexual (47.2%). At the inclusion time 26.6% of the patients had AIDS events, 60.9% were anti-HCV negative, and 91.5% had HIV RNA <50 copies/mL (84.3% for ≥1 year); 10.9% had >2 comorbidities, and 13.3% were receiving >5 non-HIV drugs. Frailty patients had a higher age (p 0.006), more sensitive deficits (visual or auditory) (p 0.002), a greater number of falls during the previous year (p 0.0001), a higher Charlson comorbidity index (p 0.001), and a higher VACS index (p 0.001). All comorbidities, excluding bone and liver, were significantly more frequent in fragile patients. The presence of >2 comorbidities and treatment with >5 drugs not related to HIV they were also more frequent in frail patienst (p 0.0001 and p 0.004, respectively). Independent predictors of pre-frailty/frailty in the multivariable analysis differ in men (VACS index, C-reactive protein [CRP], and falls) and women (CRP, AIDS, and menopause). Patients with pre-frailty/frailty had some indicator of a lower QoL. CONCLUSION: Factors associated with pre-frailty/frailty in HIV-infected patients differ by gender, which should be considered when establishing measures for prevention. The role of menopause in the risk of pre-frailty/frailty warrants further investigations.

Rate of cardiovascular, renal and bone disease and their major risks factors in HIV-infected individuals on antiretroviral therapy in Spain.

BACKGROUND: The life expectancy of HIV-infected individuals has dramatically improved with potent antiretroviral therapies. However, organ-specific toxicities of some antiretrovirals and persistent inflammation and immune activation due to residual virus replication account for a high burden of age-associated comorbidities in the HIV population. METHODS: The prevalence of overt cardiovascular, renal and bone diseases as well as their major risk factors were cross-sectionally examined during the year 2014 in the VACH cohort, a large nationwide population of HIV-infected individuals in Spain. RESULTS: A total of 10,897 HIV-infected patients were examined. Seventy-one point four percent were male and the mean age was 48 years. Mean time since HIV diagnosis was 15.8 years and mean time on antiretroviral therapy was 13.1 years. The proportion of patients with undetectable viral load was 87.1%, whereas 65.7% had CD4 counts>500 cells/mm3. Overall, cardiovascular, renal and bone disease were recorded in 4.7%, 5.9% and 2.8%, respectively. The prevalence of major risk factors was as follows: smoking 51.3%, alcohol abuse 7.8%, overweight/obesity 42.2%, diabetes 19.9%, dyslipidaemia 72.6%, hypertension 25.6%, and osteoporosis 11.1%. In the subset of patients older than 55 years-old (18%), all figures for overt disease and their major risk factors were significantly greater. CONCLUSION: Major age-related medical conditions and most of their risk factors are highly prevalent in HIV-infected individuals on long-term antiretroviral therapy in Spain. Preventive actions, including careful selection of antiretroviral agents, should be prioritized in the ageing HIV population.

Role of HIV in the desire of procreation and motherhood in women living with HIV in Spain: a qualitative approach.

BACKGROUND: Improved antiretroviral treatments and decrease in vertical transmission of HIV have led to a higher number of women living with HIV to consider childbearing. However, stigma and social rejection result in specific challenges that HIV positive women with procreation intentions have to face with. Our objective was to in depth analyse elements shaping their desire for procreation and specifically investigate the impact of HIV. METHODS: A qualitative study was conducted through open interviews with 20 women living with HIV between 18 and 45 years of age, from the Spanish AIDS Research Network Cohort (CoRIS). Interviews were audio-recorded and transcribed. A content analysis was performed. RESULTS: HIV diagnosis is a turning point in women's sexual and emotional life that is experienced traumatically. HIV diagnosis is usually associated with the fear of an immediate death and the idea of social isolation. At this moment, women temporarily reject future motherhood or having a sexual life. HIV status is only disclosed to the closed social circle and partner support is essential in HIV diagnosis assimilation process. Health professionals provide information on assisted reproductive technology and on how to minimize risk of partner HIV transmission. Most of barriers for procreation acknowledged by women are not related to HIV. However, women fear vertical transmission and experience other barriers derived from HIV infection. In this context, pregnancy makes women feel themselves as "normal women" despite HIV. Motherhood is considered an element of compensation that helps them to cope with HIV diagnosis. All these elements make health professionals key actors: they provide information and support after HIV diagnosis. CONCLUSIONS: Barriers and drivers for procreation are similar among HIV positive women and general population. However, stigma and discrimination linked with HIV weigh in HIV positive women decision of motherhood. In this context, it is necessary to provide these women with the necessary counselling, guidance and resources to take decisions about procreation properly informed.

Screening for precancerous anal lesions with P16/Ki67 immunostaining in HIV-infected MSM.

BACKGROUND: Screening of anal cancer in HIV-infected MSM with anal cytology results in high rates of false positive results and elevated burden of high-resolution anoscopies. High-risk HPV up-regulates p16 and Ki67 expression in epithelial cells. We assessed the usefulness of P16/Ki-67 immunostaining cytology for the diagnosis of precancerous anal lesions. METHODOLOGY: Cross-sectional multicenter study. Concomitant anal liquid cytology with p16/Ki-67 immunostaining and HRA with biopsy of acetowhite lugol-negative lesions was performed in HIV-infected MSM. We compared the diagnostic performance of an abnormal anal cytology and p16/Ki-67 immunostaining relative to HRA-guided biopsy by logistic regression and comparison of ROC areas. RESULTS: We included 328 HIV-infected MSM. HSIL was histologically diagnosed in 72 subjects (25.1%), and 2 (0.6%) were diagnosed with anal cancer. An abnormal cytology showed a sensitivity of 95.6% and a specificity of 58.8% for the diagnosis of biopsy-proven HSIL. P16/Ki67 positivity was associated with the presence of biopsy-proven HSIL (P trend = 0.004) but with low sensitivity (41.2%) and specificity (71%). The combination of standard cytology with P16/Ki67 immunostaining did not increment the predictive value of standard cytology alone (AUC 0.685 vs. 0.673, respectively, P = 0.688). CONCLUSION: In HIV-infected MSM P16/Ki67 immunostaining does not improve the diagnostic accuracy of anal cytology, which shows a high sensitivity yet poor specificity. Other approaches aimed at improving the diagnostic accuracy of current techniques for the diagnostic of precancerous HSIL are warranted.

Maraviroc ameliorates the increased adipose tissue macrophage recruitment induced by a high-fat diet in a mouse model of obesity.

BACKGROUND: Any strategy designed to decrease the macrophage content in adipose tissue (AT) is of great value as a way to decrease inflammation in this fat depot and also as a way to prevent or treat obesity and associated disorders. Maraviroc (MVC), a CCR5 antagonist approved for the treatment of HIV-infected patients, has beneficial effects on metabolism. The objective of this study was to investigate the effects of MVC on AT macrophage recruitment in a mouse model of obesity. The plausible underlying mechanisms of action were also investigated. METHODS: 32 male C57BL/6 mice were randomly assigned to the following groups: control, MVC (300 mg/l MVC in drinking water), high-fat diet (HFD) or HFD+MVC. After 16 weeks of treatment, histopathological and molecular analyses were performed on epididymal fat. RESULTS: Our results demonstrated that MVC reduced the presence of macrophages in epididymal fat despite the ingestion of an HFD. The inhibition of MCP-1 gene expression and JNK signalling pathway along with the upregulation of protective cytokines such as cardiotrophin-1 could contribute to these actions. MVC effects on AT macrophage recruitment were associated with a lower body weight gain and a partial improvement in insulin resistance despite an HFD. CONCLUSIONS: We have demonstrated the ability of MVC to ameliorate the increased AT macrophage recruitment induced by an HFD in a mouse model of obesity. These actions could be of interest when designing antiretroviral treatments in HIV-patients.

Aging in HIV-Infected Subjects: A New Scenario and a New View.

The prevalence of HIV-infected people aged 50 years or older is increasing rapidly; the proportion will increase from 28% to 73% in 2030. In addition, HIV-infected individuals may be more vulnerable to age-related condition. There is growing evidence that the prevalence of comorbidities and other age-related conditions (geriatric syndromes, functional or neurocognitive/mental problems, polypharmacy, and social difficulties) is higher in the HIV-infected population than in their uninfected counterparts. However, despite the potential impact of this situation on health care, little information exists about the optimal clinical management of older HIV-infected people. Here we examine the age-related conditions in older HIV-infected persons and address clinical management according to author expertise and published literature. Our aim is to advance the debate about the most appropriate management of this population, including less well-studied aspects, such as frequency of screening for psychological/mental and social and functional capabilities.

Impact of late presentation of HIV infection on short-, mid- and long-term mortality and causes of death in a multicenter national cohort: 2004-2013.

OBJECTIVES: To analyze the impact of late presentation (LP) on overall mortality and causes of death and describe LP trends and risk factors (2004-2013). METHODS: Cox models and logistic regression were used to analyze data from a nation-wide cohort in Spain. LP is defined as being diagnosed when CD4 < 350 cells/ml or AIDS. RESULTS: Of 7165 new HIV diagnoses, 46.9% (CI95%:45.7-48.0) were LP, 240 patients died. First-year mortality was the highest (aHRLP.vs.nLP = 10.3[CI95%:5.5-19.3]); between 1 and 4 years post-diagnosis, aHRLP.vs.nLP = 1.9(1.2-3.0); and >4 years, aHRLP.vs.nLP = 1.5(0.7-3.1). First-year's main cause of death was HIV/AIDS (73%); and malignancies among those surviving >4 years (32%). HIV/AIDS-related deaths were more likely in LP (59.2% vs. 25.0%; p < 0.001). LP declined from 55.9% (2004-05) to 39.4% (2012-13), and reduced in 46.1% in men who have sex with men (MSM) and 37.6% in heterosexual men, but increased in 22.6% in heterosexual women. Factors associated with LP: sex (ORMEN.vs.WOMEN = 1.4[1.2-1.7]); age (OR31-40.vs.<30 = 1.6[1.4-1.8], OR41-50.vs.<30 = 2.2[1.8-2.6], OR>50.vs.<30 = 3.6[2.9-4.4]); behavior (ORInjectedDrugUse.vs.MSM = 2.8[2.0-3.8]; ORHeterosexual.vs.MSM = 2.2[1.7-3.0]); education (ORPrimaryEducation.vs.University = 1.5[1.1-2.0], ORLowerSecondary.vs.University = 1.3[1.1-1.5]); and geographical origin (ORSub-Saharan.vs.Spain = 1.6[1.3-2.0], ORLatin-American.vs.Spain = 1.4[1.2-1.8]). CONCLUSIONS: LP is associated with higher mortality, especially short-term- and HIV/AIDS-related mortality. Mid-term-, but not long-term mortality, remained also higher in LP than nLP. LP decreased in MSM and heterosexual men, not in heterosexual women. The groups most affected by LP are low educated, non-Spanish and heterosexual women.

High prevalence of asymptomatic carriers of Tropheryma whipplei in different populations from the North of Spain.

INTRODUCTION: Tropheryma whipplei is the causative agent of Whipple disease. T. whipplei has also been detected in asymptomatic carriers with a very different prevalence. To date, in Spain, there are no data regarding the prevalence of T. whipplei in a healthy population or in HIV-positive patients, or in chronic fatigue syndrome (CFS). Therefore, the aim of this work was to assess the prevalence of T. whipplei in stools in those populations. METHODS: Stools from 21 HIV-negative subjects, 65 HIV-infected, and 12 CFS patients were analysed using real time-PCR. HIV-negative and positive subjects were divided into two groups, depending on the presence/absence of metabolic syndrome (MS). Positive samples were sequenced. RESULTS: The prevalence of T. whipplei was 25.51% in 98 stool samples analysed. Prevalence in HIV-positive patients was significantly higher than in HIV-negative (33.8% vs. 9.09%, p=0.008). Prevalence in the control group with no associated diseases was 20%, whereas no positive samples were observed in HIV-negative patients with MS, or in those diagnosed with CFS. The prevalence observed in HIV-positive patients without MS was 30.35%, and with MS it was 55.5%. The number of positive samples varies depending on the primers used, although no statistically significant differences were observed. CONCLUSIONS: There is a high prevalence of asymptomatic carriers of T. whipplei among healthy and in HIV-infected people from Spain. The role of T. whipplei in HIV patients with MS is unclear, but the prevalence is higher than in other populations.

Off-label use of maraviroc in clinical practice.

Maraviroc is a first-in-class selective CCR5 antagonist only approved in combination with other antiretrovirals for the treatment of HIV-infection. However, sometimes, off-label prescribing is necessary. In this regard, interesting data have been obtained with maraviroc from studies using murine models. In human daily clinical practice there are many researching areas of interest where CCR5 could play an important role. Nowadays few clinical trials are evaluating maraviroc's role in non-HIV-infected patients but there are many open issues that need to be answered about CCR5 antagonists. In this article we review some of them.

The efficacy and safety of maraviroc addition to a stable antiretroviral regimen in subjects with suppressed plasma HIV-RNA is not influenced by age.

There are few data about the immunovirological efficacy, safety/tolerability, and durability of maraviroc (MVC) addition to aging patients on suppressive antiretroviral therapy (cART) and undetectable viral load (<50 copies/ml). The aging population is underrepresented in most HIV clinical trials. This study included 80 patients aged ≥50 years and 161 aged <50 years and showed that after 48 weeks of treatment, there was no between-group differences in the median increase of CD4(+) T cells or the virological suppression rate. Safety and tolerability were also comparable. In multivariable analysis, the effect of age was not modified and was independent of the response to MVC. An immunological recovery of ≥100 CD4(+) T cells was significantly less common in those with a longer HIV history (≥15 years) (OR 0.43; p=0.016) or having <200/mm(3) CD4(+) T cells at MVC initiation (OR 0.27; p=0.004). Meanwhile, achieving a CD4/CD8 ratio ≥0.5 at week 48 was less likely in those with CD4(+) T cell counts <200 at MVC initiation (OR 0.09; p<0.0001) or with a previous AIDS event (OR 0.43; p=0.028). In summary, the immunovirological efficacy, safety/tolerability, and durability of MVC addition in patients virologically suppressed were independent of the patient's age at treatment onset.

Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.

Executive summary of the GeSIDA/National AIDS Plan consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2014).

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with clinical circumstances, number of CD4 cells, comorbid conditions and prevention of transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).

iMODS: internal coordinates normal mode analysis server.

Normal mode analysis (NMA) in internal (dihedral) coordinates naturally reproduces the collective functional motions of biological macromolecules. iMODS facilitates the exploration of such modes and generates feasible transition pathways between two homologous structures, even with large macromolecules. The distinctive internal coordinate formulation improves the efficiency of NMA and extends its applicability while implicitly maintaining stereochemistry. Vibrational analysis, motion animations and morphing trajectories can be easily carried out at different resolution scales almost interactively. The server is versatile; non-specialists can rapidly characterize potential conformational changes, whereas advanced users can customize the model resolution with multiple coarse-grained atomic representations and elastic network potentials. iMODS supports advanced visualization capabilities for illustrating collective motions, including an improved affine-model-based arrow representation of domain dynamics. The generated all-heavy-atoms conformations can be used to introduce flexibility for more advanced modeling or sampling strategies. The server is free and open to all users with no login requirement at http://imods.chaconlab.org.

Anal human papillomavirus genotype distribution in HIV-infected men who have sex with men by geographical origin, age, and cytological status in a Spanish cohort.

Knowledge of human papillomavirus (HPV) type distribution in populations at risk for anal cancer is needed. Here, we describe the anal HPV genotype distribution in a large Spanish cohort (Cohort of the Spanish HIV Research Network HPV [CoRIS-HPV]) of HIV-positive men who have sex with men (MSM) according to geographical origin, age, and cytological status. A cross-sectional analysis of baseline data from 1,439 HIV-infected MSM (2007 to 2012) was performed. Anal HPV genotyping was performed using the Linear Array HPV genotyping test. Descriptive analyses of subject characteristics, prevalences, and 95% confidence intervals (CI) were performed. The global prevalences of HPV, high-risk HPV (HR-HPV), and low-risk HPV (LR-HPV) types were 95.8%, 83.0%, and 72.7%, respectively. Among the HR-HPV types, HPV16 was the most common, followed by HPV59, -39, -51, -18, and -52. The prevalence of multiple HR-HPV infections was 58.5%. There were no differences in the crude analyses between Spanish and Latin-American MSM for most HPV types, and a peak in prevalence for most HPV types was seen in patients in their late thirties. Globally and by specific HPV groups, men with abnormal anal cytologies had a higher prevalence of infection than those with normal cytologies. This study has the largest number of HIV-positive MSM with HPV genotype data analyzed according to cytological status as far as we know. The information gained from this study can help with the design of anal cancer prevention strategies in HIV-positive patients.