Introduction Of cART Research Articles

Trajectory of cognitive performance among virologically suppressed aging people living with HIV

AbstractBackgroundDespite the success of combination antiretroviral therapy (cART), cognitive impairment remains a problem for people living with HIV (PLWH), including those who are virologically suppressed. The presentation and course of cognitive impairment have changed significantly since the introduction of cART. We aimed to determine the trajectory of cognitive performance in a cohort of virologically suppressed aging PLWH.MethodThai PLWH aged ≥50 years followed in the HIV‐NAT 006 cohort were enrolled during 2015‐2017 to assess cognitive performance using the Thai‐validated Montreal Cognitive Assessment (MoCA), a cutoff of ≥25 as normal. The follow‐up MoCA was consecutively performed since 2021. Participants who had plasma HIV RNA of ≤50 copies/mL and completed the follow‐up MoCA were included in the analysis. Changes in the MoCA scores were calculated between the two visits.ResultAmong 181 eligible participants (69 [38.1%] female; mean [SD] age, 57.0 [5.7] years; 46 [25.4%] had education ≤6 years; mean duration of HIV infection, 18.0 [4.2] years), 104 (57.5%) had cognitive impairment at enrollment. There were statistically significantly higher proportion of female sex (45.2% vs 28.6%, p = 0.023) and participants who had education >6 years (85.6% vs 59.4%, p<0.001) among cognitively impaired (CI) than cognitively unimpaired (CU) participants. After mean 5.6 (0.4) years of follow‐up period, the mean difference of the MoCA score was ‐0.72 (95%CI ‐1.29 to ‐0.15, p = 0.01, d = 0.19) and there were statistically significant differences in the MoCA score changes between groups categorized by baseline cognitive performance (mean difference 3.25, 95%CI 2.09 to 4.41, p<0.001, after adjusting for sex assigned at birth, age, education levels, smoking status, depression, hypertension, and diabetes mellitus).The CU group showed a statistically significant decrease in the MoCA score (mean difference ‐2.58, 95%CI ‐3.26 to ‐1.90, p<0.001, d = 0.86), and 43/77 (55.8%) of CU participants developed cognitive impairment at follow‐up, while the CI group had comparable MoCA scores between the two visits (mean difference 0.65, p = 0.09) (figure).ConclusionCU virologically suppressed PLWH demonstrated a statistically significant reduction in cognitive performance compared to their CI counterparts over time. Further studies on the underlying pathological mechanisms and implementation of cognitive care services among virologically suppressed PLWH are warranted.

Diffuse Large B-Cell Lymphoma in the HIV Setting.

Despite the widespread use of combined antiretroviral therapy (cART) and the subsequent decrease in AIDS-defining cancers, HIV-related lymphomas remain a leading cause of morbidity and mortality in people with HIV (PWH). Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) subtype in PWH. This lymphoma is a heterogeneous disease including morphological variants and molecular subtypes according to the cell of origin or the mutation profile. In the pre-cART era, treatment with standard-dose chemotherapy induced high rates of toxicity and outcomes were very poor. The introduction of cART and the incorporation of infection prophylaxis allowed the use of conventional intensive chemotherapy regimens used in the general population, such as R-CHOP or R-EPOCH. The use of cART during chemotherapy treatment was initially controversial due to the potential risk of adverse drug-drug interactions. However, the availability of current cART regimens with less potential to cause drug interactions and evidence that cART improves survival rates in NHL strongly support the use of cART in PWH with DLBCL. Consequently, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PWH with NHL.

The Many Faces of Immune Activation in HIV-1 Infection: A Multifactorial Interconnection.

Chronic immune activation has a significant role in HIV-1 disease pathogenesis and CD4+ T-cell depletion. The causes of chronic inflammation and immune activation are incompletely understood, but they are likely multifactorial in nature, involving both direct and indirect stimuli. Possible explanations include microbial translocation, coinfection, and continued presence of competent replicating virus. In fact, long-term viral suppression treatments are unable to normalize elevated markers of systemic immune activation. Furthermore, high levels of pro-inflammatory cytokines increase susceptibility to premature aging of the immune system. The phenomenon of "inflammaging" has begun to be evident in the last decades, as a consequence of increased life expectancy due to the introduction of cART. Quality of life and survival have improved substantially; however, PLWH are predisposed to chronic inflammatory conditions leading to age-associated diseases, such as inflammatory bowel disease, neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities, and non-HIV-associated cancers. Several approaches have been studied in numerous uncontrolled and/or randomized clinical trials with the aim of reducing immune activation/inflammatory status in PLWH, none of which have achieved consistent results.

A Lower CD4 Count Predicts Most Causes of Death except Cardiovascular Deaths. The Austrian HIV Cohort Study.

(1) Objective: To investigate changes in mortality rates and predictors of all-cause mortality as well as specific causes of death over time among HIV-positive individuals in the combination antiretroviral therapy (cART) era. (2) Methods: We analyzed all-cause as well as cause-specific mortality among the Austrian HIV Cohort Study between 1997 and 2014. Observation time was divided into five periods: Period 1: 1997–2000; period 2: 2001–2004; period 3: 2005–2008; period 4: 2009–2011; and period 5: 2012–2014. Mortality rates are presented as deaths per 100 person-years (d/100py). Potential risk factors associated with all-cause mortality and specific causes of death were identified by using multivariable Cox proportional hazard models. Models were adjusted for time-updated CD4, age and cART, HIV transmission category, population size of residence area and country of birth. To assess potential nonlinear associations, we fitted all CD4 counts per patient using restricted cubic splines with truncation at 1000 cells/mm3. Vital status of patients was cross-checked with death registry data. (3) Results: Of 6848 patients (59,704 person-years of observation), 1192 died: 380 (31.9%) from AIDS-related diseases. All-cause mortality rates decreased continuously from 3.49 d/100py in period 1 to 1.40 d/100py in period 5. Death due to AIDS-related diseases, liver-related diseases and non-AIDS infections declined, whereas cardiovascular diseases as cause of death remained stable (0.27 d/100py in period 1, 0.10 d/100py in period 2, 0.16 d/100py in period 3, 0.09 d/100py in period 4 and 0.14 d/100py in period 5) and deaths due to non-AIDS-defining malignancies increased. Compared to latest CD4 counts of 500 cells/mm3, lower CD4 counts conferred a higher risk of deaths due to AIDS-related diseases, liver-related diseases, non-AIDS infections and non-AIDS-defining malignancies, whereas no significant association was observed for cardiovascular mortality. Results were similar in sensitivity analyses where observation time was divided into two periods: 1997–2004 and 2005–2014. (4) Conclusions: Since the introduction of cART, risk of death decreased and causes of death changed. We do not find evidence that HIV-positive individuals with a low CD4 count are more likely to die from cardiovascular diseases.

Estimation of Health-State Utility Values and Factors Driving Health-Related Quality of Life in People Living with HIV and AIDS and Receiving cART in Germany: Baseline Analysis of a Cohort Study

HIV has become a chronic disease since widespread of combined antiretroviral therapy (cART). Understanding the influence of therapeutic and preventive interventions on health-related quality of life (HRQoL) of people living with HIV and AIDS (PLWHA) is important. Information about health state utilities and HRQoL in PLWHA after the introduction of cART is limited, especially in Germany. The study aims to estimate and describe health state utilities and HRQoL in PLWHA in Germany and explore the effects of patient characteristics, clinical and treatment factors. Utilities and HRQoL in PLWHA in Germany were measured with the generic EQ-5D-3L questionnaire. Health state utilities were calculated based on the EQ-5D descriptive system using the German EQ-5D-3L time trade-off (TTO) value set. HRQoL was calculated based on the EQ visual analogue scale (EQ-VAS). Extensive descriptive analyses were performed to represent utility values for different groups of the patients. Generalized linear models (GLMs) with beta-inflated distributions were used to determine patient characteristics and clinical factors that influence TTO utilities and VAS scores. 1056 PLWHA completed the EQ-5D-3L questionnaires at the beginning of the study. The mean TTO utility value is 0.912 (SD ± 0.154), and the mean VAS HRQoL is 84.32 (SD ± 18.55). “Anxiety/depression” and “pain/physical discomfort” are the most affected dimensions. A longer period of living with HIV, a lower CD4-cell count, having symptomatic HIV or AIDS and an increased number of changes in therapy are associated with decreased utilities and a lower probability of having HRQoL of perfect health. No significant effect of duration of regimen was found. Depression significantly decreases TTO utility values. Higher education, full-time employment and female gender are associated with higher utilities. The resulted EQ-VAS values for PLWHA in Germany are comparable with EQ-VAS estimates for the general population. The obtained estimates can be used as inputs for health economic evaluations of HIV-interventions. Addressing anxiety and depression may reduce the quality of life impairment in PLWHA. Impact of comorbidities needs further investigation.

Do Combination Antiretroviral Therapy Regimens for HIV Infection Feature Diverse T-Cell Phenotypes and Inflammatory Profiles?

Immune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature review is to understand whether cART regimens account for qualitative differences in immune reconstitution. Many studies have reported differences in T-cell homeostasis, inflammation, coagulation, and microbial translocation parameters across cART classes and in the course of triple vs dual regimens, yet such evidence is conflicting and not consistent. Possible reasons for discrepant results in the literature are the paucity of randomized controlled clinical trials, the relatively short follow-up of observational studies, the lack of clinical validation of the numerous inflammatory biomarkers utilized, and the absence of research on the effects of cART in tissues. We are currently thus unable to establish if cART classes and regimens are truly accountable for the differences observed in immune/inflammation parameters in different clinical settings. Questions still remain as to whether an early introduction of cART, specifically in the acute stage of disease, or newer drugs and novel dual drug regimens are able to significantly impact the quality of immune reconstitution and the risk of disease progression in HIV-infected subjects.

HIV-associated neurocognitive disorder and HIV-associated myelopathy in a patient with a preserved CD4, but high viral load-a rarely reported phenomenon: a case report and literature review

BackgroundDespite widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive disorder (HAND) and HIV-associated myelopathy (HAM) are not showing significant reduction in there occurrence. The HAM is a progressive myelopathy that often occur synchronously with severe form of the HAND in patients’ having advanced immunosuppression. However, co-existence of less severe form of the HAND and HAM in patient with relatively preserved CD4 cells is rarely reported clinical entity in post cART era.Case presentationWe report a 16-year old male, acquired HIV infection vertically, was on second line regimen because of virological failure since 3 years. His current CD4 lymphocyte count is 835 cells/uL with viral RNA level of 33,008 copies/mL. Currently presented with progressive forgetfulness, gait imbalance, and a frequent staring episodes without loss of postural tone. Neurological examination was pertinent for cognitive dysfunction with score of 6 on International HIV Dementia Scale (motor speed = 3, psychomotor speed = 2, and memory recall = 1). Lower limbs power is 4−/5, increased deep tendon reflexes, and unsteady gait. Brain MRI revealed diffuse both cortical and white matter T2 and FLAIR hyperintense lesions. Thoracic MRI showed abnormal T2 signal prolongation spanning from mid thoracic cord to conus. Electroencephalography study showed severe generalized slowing with evidence of focal dysrhythmia in bilateral frontotemporal regions. Unremarkable serum vitamin B 12 level (286 ng/mL). Virological failure with the HAND, HAM and seizure was considered. Dolutegravir +3TC + ATV/r regimen and valproate for seizure disorder was started. On 6 months follow up evaluation, he is clinically stable with significant improvement of his symptoms related to seizure disorders and modest improvement of his cognitive dysfunction, as he is now attending his school regularly. However, less improvement was observed reading his gait abnormality.ConclusionThis case supports the current understanding regarding the persistent occurrence of HIV-associated neurocognitive disorder and HIV-associated myelopathy even decades after introduction of cART. Therefore, it’s important to screen HIV+ patients for the HAND and HAM even if they have relatively preserved immunity. Because patient can be easily shifted to ART drugs with better CNS penetrating potential to achieve acceptable virological suppression level, to observe sound clinical improvement.

Mortality from suicide among people living with HIV and the general Swiss population: 1988-2017.

IntroductionIn many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the introduction of triple combination antiretroviral therapy (cART), and to identify risk factors associated with death from suicide in Switzerland.MethodsWe analysed data from the Swiss HIV Cohort Study from the pre‐cART (1988‐1995), earlier cART (1996‐2008) and later cART (2009‐2017) eras. We used multivariable Cox regression to assess risk factors for death due to suicide in the ART era and computed standardized mortality ratios (SMRs) to compare mortality rates due to suicide among persons living with HIV with the general population living in Switzerland, using data from the Swiss National Cohort.Results and DiscussionWe included 20,136 persons living with HIV, of whom 204 (1.0%) died by suicide. In men, SMRs for suicide declined from 12.9 (95% CI 10.4‐16.0) in the pre‐cART era to 2.4 (95% CI 1.2‐5.1) in the earlier cART and 3.1 (95% CI 2.3‐4.3) in the later cART era. In women, the corresponding ratios declined from 14.2 (95% CI 7.9‐25.7) to 10.2 (3.8‐27.1) and to 3.3 (95% CI 1.5‐7.4). Factors associated with death due to suicide included gender (adjusted hazard ratio 0.58 (95% CI 0.38‐0.87) comparing women with men), nationality (1.95 (95% CI 1.34‐2.83) comparing Swiss with other), Centers for Disease Control and Prevention clinical stage (0.33 (95% CI 0.24‐0.46) comparing stage A with C), transmission group (2.64 (95% CI 1.71‐4.09) for injection drug use and 2.10 (95% CI 1.36‐3.24) for sex between men compared to other), and mental health (2.32 (95% CI 1.71‐3.14) for a history of psychiatric treatment vs. no history). There was no association with age.ConclusionsSuicide rates have decreased substantially among people living with HIV in the last three decades but have remained about three times higher than in the general population since the introduction of cART. Continued emphasis on suicide prevention among men and women living with HIV is important.

Does HIV infection contribute to increased beta-amyloid synthesis and plaque formation leading to neurodegeneration and Alzheimer's disease?

HIV infection in the combination antiretroviral therapy (cART) era has become a chronic disease with a life expectancy almost identical to those free from this infection. Concomitantly, chronic diseases such as neurodegenerative diseases have emerged as serious clinical problems. HIV-induced cognitive changes, although clinically very diverse are collectively called HIV-associated neurocognitive disorder (HAND). HAND, which until the introduction of cART manifested clinically as a subcortical disorder, is now considered primarily cognitive disorder, which makes it similar to diseases like Alzheimer's (AD) and Parkinson's disease (PD). The pathogenesis involves either the direct effects of the virus or the effect of viral proteins such as Tat, Ggp120, and Nef. These proteins are either capable of destroying neurons directly by inducing neurotoxic mediators or by initiating neuroinflammation by microglia and astrocytes. Recently, it has become recognized that HIV infection is associated with increased production of the beta-amyloid peptide (Aβ) which is a characteristic of AD. Moreover, amyloid plaques have also been demonstrated in the brains of patients suffering from HAND. Thus, the question arises whether this production of Aβ indicates that HAND may lead to AD or it is a form of AD or this increase in Aβ production is only a bystander effect. It has also been discovered that APP in HIV and its metabolic product Aβ in AD manifest antiviral innate immune peptide characteristics. This review attempts to bring together studies linking amyloid precursor protein (APP) and Aβ production in HIV infection and their possible impact on the course of HAND and AD. These data indicate that human defense mechanisms in HAND and AD are trying to contain microorganisms by antimicrobial peptides, however by employing different means. Future studies will, no doubt, uncover the relationship between HAND and AD and, hopefully, reveal novel treatment possibilities.

Hiv and Lymphoma: from Epidemiology to Clinical Management.

Patients infected with human immunodeficiency virus (HIV) are at increased risk for developing both non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). Even if this risk has decreased for NHL after the introduction of combination antiretroviral therapy (cART), they remain the most common acquired immune deficiency syndrome (AIDS)-related cancer in the developed world. They are almost always of B-cell origin, and some specific lymphoma types are more common than others. Some of these lymphoma types can occur in both HIV-uninfected and infected patients, while others preferentially develop in the context of AIDS. HIV-associated lymphoma differs from lymphoma in the HIV negative population in that they more often present with advanced disease, systemic symptoms, and extranodal involvement and are frequently associated with oncogenic viruses (Epstein-Barr virus and/or human herpesvirus-8). Before the introduction of cART, most of these patients could not tolerate the treatment strategies routinely employed in the HIV-negative population. The widespread use of cART has allowed for the delivery of full-dose and dose-intensive chemotherapy regimens with improved outcomes that nowadays can be compared to those seen in non-HIV infected patients. However, a great deal of attention should be paid to opportunistic infections and other infectious complications, cART-chemotherapy interactions, and potential cumulative toxicity. In the context of relatively sparse prospective and randomized trials, the optimal treatment of AIDS-related lymphomas remains a challenge, particularly in patients with severe immunosuppression. This paper will address epidemiology, pathogenesis, and therapeutic strategies in HIV-associated NHL and HL.

Opportunistic ocular infections in the setting of HIV.

The aim of this review is to highlight recent changes in opportunistic ocular infections (OOIs) in the era of modern combination antiretroviral therapy (cART), in the setting of HIV-infected patients. Improvements in modern cART has led to a progressive decline in the incidence of OOIs and mortality among patients with AIDS. Not only has there been a decreasing incidence of cytomegalovirus (CMV) retinitis, but there also has been a decline in progression of such retinitis when it does occur in AIDS patients, since the introduction of cART. Nevertheless, CMV retinitis remains the major cause of vision loss in AIDS patients. Although the incidence of CMV retinitis has declined overall, the incidence of ocular syphilis has increased during the cART era. Moreover, the impact of having HIV plays a role with respect to multidrug-resistant (MDR) tuberculosis and has resulted in a high prevalence of presumed ocular tuberculosis in HIV/MDR-TB co-infected patients. Although immune reconstitution uveitis (IRU) has been an important cause of visual deficits in developed countries, OOIs remain an important cause of blindness in the developing world. Reconstituting the immune system with effective cART while increasing accessibility of screening examinations is key to the success of blindness prevent in HIV-infected individuals, particularly in developing countries.

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study.

Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS).Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20–29 years old), group 2 (30–39), group 3 (40–49) and group 4 (50–59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson’s correlation test. Statistical significance was set at p < 0.05.Results: The NAA/Cr ratios were decreased in the 20–29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50–59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations.Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART.Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.

Epidemiological trends of deep venous thrombosis in HIV-infected subjects (1997–2013): A nationwide population-based study in Spain

BackgroundChronic infections may be a triggering factor as well as a risk factor of deep venous thrombosis (DVT). The purpose of this study was to analyze the epidemiological trends of hospital admissions related to DVT in human immunodeficiency virus (HIV)-infected patients during the combination antiretroviral therapy (cART) era, in relation to hepatitis C virus (HCV) serological status. MethodsWe performed a retrospective study using the Spanish Minimum Basic Data Set. We selected HIV-infected subjects over 15years old with a hospital admission and DVT diagnosis (ICD-9-CM codes: 453.4x and 453.8x) between 1997 and 2013. Patients were classified according to HCV serology. We estimated the incidence (events per 100,000 patient-years) in four calendar periods (1997–1999, 2000–2003, 2004–2007, and 2008–2013). ResultsOverall, the incidence of DVT-related hospitalizations had a significant upward trend in all HIV-infected patients (P<0.001), with significant differences between 1997–1999 and 2008–2013 [49.5 vs. 88.1 (P<0.001)]. Moreover, the incidence was higher in HIV-monoinfected patients than in HIV/HCV-coinfected patients during the entire follow-up (P<0.001). However, the incidence had a significant downward trend in HIV-monoinfected patients (P=0.002) and a significant upward trend in HIV/HCV-coinfected patients (P<0.001). Specifically, the incidence of DVT-related hospitalizations in HIV-monoinfected patients significantly decreased from 1997–1999 to 2008–2013 [142.7 vs. 103.1 (P=0.006)], whereas in HIV/HCV-coinfected patients, the incidence increased from 8.4 (1997–1999) to 70.7 (2008–2013) (P<0.001). ConclusionsOur findings suggest that DVT is an emerging health problem among HIV-infected patients, with increasing incidence during the first 17years after the introduction of cART, particularly in HIV/HCV-coinfected patients.

HIV-1 matrix protein p17 and its variants promote human triple negative breast cancer cell aggressiveness

BackgroundThe introduction of cART has changed the morbidity and mortality patterns affecting HIV-infected (HIV+) individuals. The risk of breast cancer in HIV+ patients has now approached the general population risk. However, breast cancer has a more aggressive clinical course and poorer outcome in HIV+ patients than in general population, without correlation with the CD4 or virus particles count. These findings suggest a likely influence of HIV-1 proteins on breast cancer aggressiveness and progression. The HIV-1 matrix protein (p17) is expressed in different tissues and organs of successfully cART-treated patients and promotes migration of different cells. Variants of p17 (vp17s), characterized by mutations and amino acid insertions, differently from the prototype p17 (refp17), also promote B-cell proliferation and transformation.MethodsWound-healing assay, matrigel-based invasion assay, and anchorage-independent proliferation assay were employed to compare the biological activity exerted by refp17 and three different vp17s on the triple-negative human breast cancer cell line MDA-MB 231. Intracellular signaling was investigated by western blot analysis.ResultsMotility and invasiveness increased in cells treated with both refp17 and vp17s compared to untreated cells. The effects of the viral proteins were mediated by binding to the chemokine receptor CXCR2 and activation of the ERK1/2 signaling pathway. However, vp17s promoted MDA-MB 231 cell growth and proliferation in contrast to refp17-treated or not treated cells.ConclusionsIn the context of the emerging role of the microenvironment in promoting and supporting cancer cell growth and metastatic spreading, here we provide the first evidence that exogenous p17 may play a crucial role in sustaining breast cancer cell migration and invasiveness, whereas some p17 variants may also be involved in cancer cell growth and proliferation.

The Chronicity of HIV Infection Should Drive the Research Strategy of NeuroHIV Treatment Studies: A Critical Review.

HIV infection has become a chronic illness when successfully treated with combined antiretroviral therapy (cART). The long-term health prognosis of aging with controlled HIV infection and HIV-associated neurocognitive disorder (HAND) remains unclear. In this review, we propose that, almost 20 years after the introduction of cART, a change in research focus is needed, with a greater emphasis on chronicity effects driving our research strategy. We argue that pre-emptive documentation of episodes of mild neurocognitive dysfunction is needed to determine their long-term prognosis. This strategy would also seek to optimally represent the entire HAND spectrum in therapeutic trials to assess positive and/or negative treatment effects on brain functions. In the first part of the paper, to improve the standard implementation of the Frascati HAND diagnostic criteria, we provide a brief review of relevant quantitative neuropsychology concepts to clarify their appropriate application for a non-neuropsychological audience working in HIV research and wanting to conduct randomized clinical trials on brain functions. The second part comprises a review of various antiretroviral drug classes and individual agents with respect to their effects on HAND, while also addressing the question of when cART should be initiated to potentially reduce HAND incidence. In each section, we use recent observational studies and randomized controlled trials to illustrate our perspective while also providing relevant statistical comments. We conclude with a discussion of the neuroimaging methods that could be combined with neuropsychological approaches to enhance the validity of HIV neurology (neuroHIV) treatment effect studies.

P11.20 Resurgence of syphilis among hiv-infected men who have sex with men attending sti clinics in the netherlands

Introduction In the Netherlands, approximately 90% of all infectious syphilis (syphilis) and 70% of all new HIV infections are among men who have sex with men (MSM). As the relation between syphilis and HIV is characterised by a bidirectional synergy, we assessed syphilis trends among MSM stratified by HIV status. Methods The national STI/HIV surveillance contains epidemiological, behavioural and clinical data from STI clinics, which provide low threshold STI/HIV testing and care for high-risk groups. We descriptively examined syphilis positivity rates between 2007 and 2014. Results The number of MSM consultations increased each year from 11,048 in 2007 to 29,939 in 2014. Of all MSM, 83% were HIV-negative. The number of syphilis diagnoses was lowest in 2011 (n = 426) and highest in 2014 (n = 693), of which around 40% was among HIV-infected MSM each year. Among known HIV-infected MSM, the syphilis positivity rate decreased between 2007 (12.3%) and 2011 (4.5%), followed by an increase in recent years (2014: 6.6%). Among MSM newly diagnosed with HIV, this trend was roughly similar to that of known HIV-infected MSM. Among HIV-negative MSM, the syphilis positivity rate decreased between 2007 (2.8%) and 2011 (1.4%), and remained stable thereafter. Conclusion The observed rebound in syphilis rates in a high-risk group of HIV-positive MSM is concerning at individual level, given the adverse effects on both syphilis and HIV disease progression. At public health level, this is worrisome as syphilis facilitates transmission and acquisition of HIV. Therefore, syphilis infection could be indicative to offer HIV pre-exposure prophylaxis (PrEP) among HIV-negative MSM. On the other hand, offering PrEP to a high-risk core group could promote syphilis transmission if it leads to reduced perceived vulnerability and subsequent increased risk behaviour, as seen after the introduction of cART. Disclosure of interest statement The authors declare that they have no competing interests.

Female and male differences in AIDS diagnosis rates among people who inject drugs in large U.S. metro areas from 1993 to 2007

PurposeWe estimated female and male incident AIDS diagnosis rates (IARs) among people who inject drugs (PWID) in U.S. metropolitan statistical areas (MSAs) over time to assess whether declines in IARs varied by sex after combination antiretroviral therapy (cART) dissemination. MethodsWe compared IARs and 95% confidence intervals for female and male PWID in 95 of the most populous MSAs. To stabilize estimates, we aggregated data across three-year periods, selecting a period immediately preceding cART (1993–1995) and the most recent after the introduction of cART for which data were available (2005–2007). We assessed disparities by comparing IAR 95% confidence intervals for overlap, female-to-male risk ratios, and disparity change scores. ResultsIARs declined an average of 58% for female PWID and 67% for male PWID between the pre-cART and cART periods. Among female PWID, IARs were significantly lower in the later period relative to the pre-cART period in 48% of MSAs. Among male PWID, IARs were significantly lower over time in 86% of MSAs. ConclusionsIARs among female PWID in large U.S. MSAs have declined more slowly than among male PWID. This suggests a need for increased targeting of prevention and treatment programs and for research on MSA level conditions that may drive differences in declining AIDS rates among female and male PWID.

Facing up to the ongoing challenge of Kaposi's sarcoma.

Kaposi's sarcoma is a mesenchymal tumour caused by infection with human herpesvirus 8, usually in the context of immunodeficiency. The global incidence of Kaposi's sarcoma rose dramatically with the outbreak of HIV and AIDS. Although the introduction of combined antiretroviral therapy (cART) has seen a dramatic decline in Kaposi's sarcoma incidence, it remains a significant burden of morbidity and mortality, especially in sub-Saharan Africa. This review considers the most recent evidence regarding the prevalence, current treatment strategies and future therapies for Kaposi's sarcoma. In the post-cART era, the epidemiology of acquired immunodeficiency syndrome-related Karposi sarcoma (AIDS-KS) is changing, with a rising incidence in the context of immune reconstitution inflammatory syndrome, and this has important implications for cART rollout initiatives. The current best-available treatment strategies use cART either alone or in combination with systemic chemotherapy, and there is new evidence for a stage-stratified treatment algorithm to guide their use. In addition, a number of new, targeted therapies for Kaposi's sarcoma are under investigation. The introduction of cART has not entirely removed the challenge of AIDS-KS. It is, however, an increasingly manageable disease, although issues of drug availability in sub-Saharan Africa remain to be addressed.

Communication Between HIV Patients and Their Providers: A Qualitative Preference Match Analysis

Since the introduction of cART (combination antiretroviral therapy), HIV has evolved into a chronic disease such that it requires lifelong medical treatment to which patients must adhere. Communication with health care providers is pivotal in supporting patients to adapt to having HIV and adhering to treatment, in order to maintain health and quality of life. Previous research indicates that communication is optimal when it matches patient preferences for information exchange, relationship establishment, and involvement in treatment decisions. The aim of the present study is to explore HIV patient communication preferences as well as patient experiences with their providers (not) matching their preferences. A second aim is to explore provider beliefs about patient preferences and provider views on optimal communication. Data were collected through interviews with 28 patients and 11 providers from two academic hospitals. Results indicate that patient preferences reflect their cognitive, emotional, and practical needs such that patients look to increase their sense of control over their HIV. Patients aim to further increase their sense of control (by proxy) through their relationship with their providers and through their decisional involvement preferences. Providers are well aware of patient communication preferences but do not explicate underlying control needs. Implications for clinical practice are discussed.

Prevalence and predictors of malignancies in a polycentric cohort of HIV patients from Italy.

IntroductionHIV infected patients have a higher risk of developing cancer than the general population. Kaposi's sarcoma, non-Hodgkin's lymphoma, primary CNS lymphoma and invasive cervical cancers are considered as AIDS defining [1]. An increased incidence in recent years has been reported also for other malignancies after the introduction of cART [2,3].Materials and MethodsWe performed a retrospective multicentric evaluation of all HIV infected patients with both AIDS and non-AIDS defining neoplasms at six Infectious Disease Units spread throughout Italy since 1991 through 2013. Cases were compared with equal number of controls without neoplasia followed at the same institutions, matched for length of HIV infection.ResultsSince 1991, 339 consecutive cases of malignancy were collected from the six convening centres, including approximately an equal proportion of AIDS (51.2%) and non-AIDS defining tumours. Mean prevalence of tumours among centres was 8.3% (r. 6.1%–9.6%). Mean age at tumour diagnosis was significantly lower than in controls (42.6±11.0 vs 46.8±10.6 years, respectively, p<0.0001). As to risk factors for HIV infection, approximately 1/4 (26.1%) of patients were drug abusers, in equal proportion as in controls. A remarkable higher proportion of cancer patients had CD4 T-cell counts <200 c/mmc at time of diagnosis (45.2% vs 13.3%, p<0.0001). Seventy percent of tumours occurred in males; 52.8% of tumour patients were diagnosed with AIDS before and 19.0% at the time of tumour diagnosis. Ninety (28.1%) tumour patients were dead at the time of data collection, a much higher proportion than among cases (12.9%, p<0.0001). Deaths among non-AIDS (20.8%) and AIDS defining tumour patients (35.0%) were significantly different (p=0.005). Predictors of AIDS defining tumours at the time of data collection were: male sex (57.9% vs 40.6%, p=0.004), CD4 T-cell counts <200 c/mmc (63.6% vs 44.1%, p<0.0001), whereas being cART treated at the time of tumour diagnosis was protective (38.0% vs 68.0%, p<0.0001). In the final multivariate model of logistic regression, male sex (OR=2.0, p=0.03) and not being cART treated (OR=2.5, p=0.001) held as independent predictors.ConclusionsOur retrospection revealed a considerably high proportion of non-AIDS defining tumours, apparently at rise in recent years. We registered high prevalence of tumours in each centre. Absence of cART seemed related with AIDS defining tumours: once more prevention of late presentation appeared the way to avoid worse prognosis in this setting.