Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. METHODS: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. RESULTS: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). CONCLUSIONS: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.

PrEP in the Context of Other HIV Risk Reduction Strategies Among Men Who Have Sex with Men: Results from the Flash! PrEP in Europe Survey.

Combination HIV prevention covers a range of biomedical, behavioral, and socio-structural interventions. Despite the growing availability of pre-exposure prophylaxis (PrEP), it is not always accessible in European Centre for Disease Prevention and Control reporting countries and may not meet the needs of all at-risk populations. Based on the Flash! PrEP in Europe data, multiple correspondence analysis and hierarchical clustering were used to identify patterns in HIV prevention strategies among 9980 men who have sex with men (MSM). PrEP interest was evaluated among four identified clusters: (A) "high condom use, sometimes Treatment as Prevention (TasP)"; (B) "mix of methods, infrequent condom use"; (C) "high condom use, tendency to choose partners based on serological status" and (D) "moderate use of condoms mixed with other prevention strategies". Clusters B and D had higher PrEP interest. These results suggest that MSM use a range of behavioral and biomedical risk reduction strategies that are often combined. On-demand PrEP may meet the needs of MSM who infrequently use condoms and other prevention methods.

Preferences of PLWH and of clinicians for HIV treatment aimed at long-term success.

This study aimed to develop a new approach to manage people living with HIV (PLWH), investigating preferences of clinicians and PLWH in order to improve linkage to care of PLWH. A survey was performed with the Discrete Choice Experiment (DCE) method to investigate the preferences of two categories, clinicians and PLWH, for attributes of HIV care pathways, therapy and quality of life. Our results suggest that the most important feature of a care pathway was the site of testing for both categories, followed by modality of counselling for clinicians and by pre-exposure prophylaxis for PLWH. Regarding therapy, choices were mostly oriented by modality of administration for both categories, and by CD4 cells increase for clinicians and side effects for PLWH. People living with HIV reported that, out of 13 candidates, the two most important factors related to good long-term quality of life would be reduction of viral transmissibility and good emotional life. A tailored approach could be the key to long-term treatment success, but this approach must necessarily be based on evaluation of the specific complexities of the patient.

Undetectable equals untransmittable (U = U): awareness and associations with health outcomes among people living with HIV in 25 countries.

OBJECTIVES: 'Undetectable equals Untransmittable' (U=U) is an empowering message that may enable people living with HIV (PLHIV) to reach and maintain undetectability. We estimated the percentage of PLHIV who ever discussed U=U with their main HIV care provider, and measured associations with health-related outcomes. Secondarily, we evaluated whether the impact of the U=U message varied between those who heard it from their healthcare provider (HCP) vs from elsewhere. METHODS: Data were from the 25-country 2019 Positive Perspectives Survey of PLHIV on treatment (n=2389). PLHIV were classified as having discussed U=U with their HCP if they indicated that their HCP had ever told them about U=U. Those who had not discussed U=U with their HCP but were nonetheless aware that 'My HIV medication prevents me from passing on HIV to others' were classified as being made aware of U=U from non-HCP sources. Multivariable logistic regression was used to measure associations between exposure to U=U messages and health outcomes. RESULTS: Overall, 66.5% reported ever discussing U=U with their HCP, from 38.0% (South Korea) to 87.3% (Switzerland). Prevalence was lowest among heterosexual men (57.6%) and PLHIV in Asia (51.3%). Compared with those unaware of U=U, those reporting U=U discussions with their HCP had lower odds of suboptimal adherence (AOR=0.59, 95% CI 0.44 to 0.78) and higher odds of self-reported viral suppression (AOR=2.34, 95% CI 1.72 to 3.20), optimal sexual health (AOR=1.48, 95% CI 1.14 to 1.92) and reporting they 'always shared' their HIV status (AOR=2.99, 95% CI 1.42 to 6.28). While exposure to U=U information from non-HCP sources was beneficial too, the observed associations were attenuated relative to those seen with reported discussions with HCPs. CONCLUSION: HCP discussion of U=U with PLHIV was associated with favourable health outcomes. However, missed opportunities exist since a third of PLHIV reported not having any U=U discussion with their HCP. U=U discussions with PLHIV should be considered as a standard of care in clinical guidelines.

Regional differences in perceived treatments needs and priorities in relation to antiretroviral therapy among people living with HIV in 25 countries.

While geographic differences in HIV burden are well documented, less is known about regional differences in perceived treatment needs. To fill this gap, the 2019 Positive Perspectives study of people living with HIV (PLHIV) was conducted in 25 countries across Northern America, Latin America, the Asian region, Europe (EU/Schengen countries), Russia, Australia, and South Africa (n = 2389). Overall mean duration of HIV was 10.1 (SD = 9.6) years. The perception that HIV had a negative impact on day-to-day life was lowest among participants from South Africa (14.0%[25/179]) and highest among participants from the Asian region (55.2%[127/230]). Most of the regional gap in the perception that HIV had a negative impact on daily life was explained by regional differences in medication-related unmet needs, stigma, demographic factors, and comorbidities. The percentage who felt they understood their treatment was highest among participants from Australia (87.5%[105/120]) and lowest among those from Russia (62.0%[93/150]), the Asian region (62.2%[143/230]), and South Africa (62.6%[112/179]). Among participants from Northern America, Europe, and Latin America, the treatment goals with the largest absolute increase in perceived importance, from time of starting treatment to time of survey among those diagnosed for ≥1 year, were minimizing the long term impact of antiretroviral treatment and keeping the number of medicines in their antiretroviral regimen at a minimum. Tailored approaches to care of PLHIV are needed as different regions have different disease burden and treatment needs. Equitable approaches to HIV care are needed across and within regions to ensure that patients' unmet needs and preferences are addressed to improve their overall wellbeing and health-related quality of life.

Physical, Emotional, and Psychosocial Challenges Associated with Daily Dosing of HIV Medications and Their Impact on Indicators of Quality of Life: Findings from the Positive Perspectives Study.

To assess challenges with daily oral antiretroviral therapy (ART), we analyzed data for 2389 participants in the 2019 Positive Perspectives survey of people living with HIV in 25 countries. ART-related challenges reported included difficulty swallowing pills (33.1% [790/2389]); stress from daily dosing routine (33.3% [795/2389]); bad memories from daily intake of HIV medication (35.1%[839/2389]), and concern "that having to take pills every day means a greater chance of revealing my HIV status to others" (37.9% [906/2389]). Individuals who felt empowered by daily oral dosing ["taking my pill(s) every day reassures me that my HIV is being kept under control"] had 69% higher odds of optimal overall health (AOR 1.69, 95% CI 1.40-2.04). Conversely, odds of optimal overall health were lower among those who felt daily pill intake "limits my day-to-day life" (AOR 0.53, 95% CI 0.44-0.64). These findings show that there is need for increased flexibility of ART delivery to meet diverse patient needs.

Shared Decision Making Between Patients and Healthcare Providers and its Association with Favorable Health Outcomes Among People Living with HIV.

We assessed patient-provider communication in HIV care; data were from the 2019 Positive Perspectives Survey of people living with HIV (PLHIV) from 25 countries (n = 2389). A significantly greater proportion of recently diagnosed individuals were interested in being involved when it comes to decisions about their HIV treatment compared with any other group (72.8% [399/548], 63.1% [576/913], and 62.6% [581/928], diagnosis year: 2017-2019, 2010-2016, and pre-2010 respectively) but reported less understanding of their treatment compared with those reporting the longest duration (66.8% [366/548], 68.6% [626/913], and 77.3% [717/928], respectively). One-third of PLHIV with salient treatment-related concerns were uncomfortable discussing with providers. Of participants who felt that their HIV medication limited their life but did not discuss their concerns with their provider (n = 203), top reasons for not discussing were: perception nothing could be done (49.3% [100/203]), provider never brought up the issue (37.9% [77/203]), and not wanting to appear difficult (30.5% [62/203]). To continue to identify and address unmet treatment needs among PLHIV, providers need to ensure that there is ongoing open dialogue.

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

Prevalence, determinants, and impact of suboptimal adherence to HIV medication in 25 countries.

Modern antiretroviral therapy (ART) has improved the lives of people living with HIV (PLHIV) but currently requires daily adherence. We assessed prevalence and correlates of suboptimal adherence, and measured associations with self-reported health outcomes. Data were from web-based surveys of confirmed HIV+ adults on antiretroviral treatment within 25 countries during 2019 (n = 2389). Suboptimal adherence was a report of ≥1 reason for missing ART ≥5 times within the past month. Multivariable logistic regression examined associations between suboptimal adherence and self-reported overall health and virologic suppression. Overall, 24.1% (575/2389) reported suboptimal adherence, from 10.0% (5/50) in Austria, to 62.0% (31/50) in China. The most common reasons for missing ART ≥5 times in the overall population were feeling depressed/overwhelmed (7.4%, 176/2389), trying to forget about HIV (7.0%, 168/2389), and work (6.1%, 145/2389). Correlates of suboptimal adherence included being heterosexual, <50 years old, ≤high school, having gastrointestinal treatment side effects, and privacy concerns. Odds of suboptimal overall health were 1.41 (95%CI, 1.11-1.80), 2.10 (95%CI, 1.65-2.68), and 2.55 (95%CI, 2.00-3.25) among those who reported the maximum number of times missed ART for any reason within the past month as 1, 2-4, or ≥5 times respectively, vs not missing at all. Odds of virologic nonsuppression were 1.80 (95%CI, 1.33-2.45), and 2.24 (95%CI, 1.66-3.02) for 2-4, or ≥5 times of missed ART respectively, vs not missing at all; missing for only 1 time was not significantly associated with virologic nonsuppression. Novel ART strategies designed to improve adherence along with interventions to empower PLHIV and support self-medication may improve health outcomes and quality of life.

Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy.

IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN, SETTING, AND PARTICIPANTS: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. EXPOSURES: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. MAIN OUTCOMES AND MEASURES: Risk of within-couple HIV transmission to the HIV-negative partner. RESULTS: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. CONCLUSIONS AND RELEVANCE: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain. METHODS: The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021. RESULTS: Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference). CONCLUSIONS: Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Partners of people on ART - a New Evaluation of the Risks (The PARTNER study): design and methods.

BACKGROUND: It is known that being on antiretroviral therapy reduces the risk of HIV transmission through sex. However it remains unknown what the absolute level of risk of transmission is in a person on ART with most recent measured HIV plasma viral load<50 c/mL in the absence of condom use. There are no data on risk of transmission for anal sex in MSM when the index partner is on ART. METHODS/DESIGN: The PARTNER study is an international, observational multi-centre study, taking place from 2010 to 2014 in which HIV serodifferent partnerships who at enrolment reported recently having had condom-less vaginal or anal sexual intercourse are followed over time, with 46 monthly reporting of transmission risk behaviour through a confidential self completed risk behaviour questionnaire and with 46 monthly HIV testing for the HIV negative partner. The objective is to study (i) the risk of HIV transmission to partners, in particular in partnerships that continue not to use condoms consistently and the HIV-positive partner is on therapy with a viral load<50 copies/mL and (ii) why some partnerships do not use condoms, to describe the proportion who begin to adopt consistent condom use, and factors associated with this. For any negative partner who becomes infected phylogenetic analysis will be used following anonymisation of the samples to assess if transmission had been from the HIV infected partner. DISCUSSION: This observational study will provide missing information on the absolute risk of HIV transmission for both vaginal and anal sex when the index case is on ART with a VL<50 copies/mL in the absence of condom use.

Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry.

BACKGROUND: Currently, no data are available on the burden of morbidity and mortality in people with HIV-1 (PWH) harboring a 4-class drug-resistant (4DR) virus (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase strand transfer inhibitors). The study aimed to assess the incidence of clinical events and death in this population. METHODS: This was a cohort study on PWH from the PRESTIGIO Registry with a documented 4DR virus. Burden of disease was defined as the occurrence of any new event including an AIDS-defining event (ADE) or non-AIDS-defining event (NADE) or death from any cause after 4DR evidence (baseline). Cox regression models evaluated factors associated with the risk of new clinical events/death. RESULTS: Among 148 PWH followed for a median (interquartile range) of 47 (32-84) months after 4DR evidence, 38 PWH had 62 new events or died from any cause (incidence rate, 9.12/100 person-years of follow-up; 95% CI = 6.85-11.39): 12 deaths (6 AIDS-related and 6 non-AIDS-related), 18 ADEs, 32 NADEs; 20 of the 38 NADEs (45%) of the incident clinical events were malignancies. The 4-year cumulative incidence of death was 6% (95% CI, 3%-13%), and that of ≥1 event or death was 22% (95% CI, 16%-31%). A higher risk of new clinical events/death was more likely in PWH with previous clinical events (adjusted hazard ratio [aHR], 2.67; 95% CI, 1.07-6.67) and marginally associated with lower baseline CD4+/CD8+ ratio (aHR, 0.82; 95% CI, 0.65-1.02). CONCLUSIONS: PWH harboring 4DR have a high burden of disease with a worrying incidence of malignancies, strongly advising for close prevention and monitoring interventions as well as access to innovative therapeutic strategies, especially in people with a history of clinical events and low CD4+/CD8+ ratio.

[Treating HIV disease: back to the patient?] / Curare la malattia da HIV: ritorno al paziente?

HIV disease has dramatically changed in the last two decades from a progressive, lethal disease to a chronic manageable condition. These changes are due to the availability of potent antiretroviral combination therapy, which also have the potential to contribute significantly to the control of the epidemic. Among persons living with HIV, incidence of immunosuppression-related opportunistic illnesses has clearly decreased, while an increase was observed in the prevalence of age-related noncommunicable comorbidities, including cardiovascular, metabolic, renal, bone and hepatic disease, due to chronic inflammatory state and to an overall aging of the population of persons with HIV. It has been predicted that by 2030 more than 80% of older persons with HIV will have at least one comorbidity, compared to 19% of non HIV-infected persons, and that one fourth of these persons will have three or more comorbidities. Among persons with HIV, the prevalence of frailty is increasing. Choice of therapeutic approach to HIV disease should take into account, in addition to the ability of drug combination to suppress viral replication, the potential for long term adherence to treatment, the lack of long term toxicity, the possibility to fully restore immune function and prevent immune activation, thus reducing the risk of chronic inflammation related disease. In addition the overall impact of treatment on patients' well-being must be considered, and patients related outcomes should be used to measure this impact.

Pulmonary effects of immediate versus deferred antiretroviral therapy in HIV-positive individuals: a nested substudy within the multicentre, international, randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial.

BACKGROUND: Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals. METHODS: We did a nested substudy within the randomised, controlled Strategic Timing of Antiretroviral Treatment (START) trial at 80 sites in multiple settings in 20 high-income and low-to-middle-income countries. Participants were HIV-1 infected individuals aged at least 25 years, naive to ART, with CD4 T-cell counts of more than 500 per µL, not receiving treatment for asthma, and without recent respiratory infections (baseline COPD was not an exclusion criterion). Participants were randomly assigned to receive ART (an approved drug combination derived from US Department of Health and Human Services guidelines) either immediately, or deferred until CD4 T-cell counts decreased to 350 per µL or AIDS developed. The randomisation was determined by participation in the parent START study, and was not specific to the substudy. Because of the nature of our study, site investigators and participants were not masked to the treatment group assignment; however, the assessors who reviewed the outcomes were masked to the treatment group. The primary outcome was the annual rate of decline in lung function, expressed as the FEV1 slope in mL/year; spirometry was done annually during follow-up for up to 5 years. We analysed data on an intention-to-treat basis, and planned separate analyses in smokers and non-smokers because of the known effects of smoking on FEV1 decline. The substudy was registered at ClinicalTrials.gov number NCT01797367. FINDINGS: Between March 11, 2010, and Aug 23, 2013, we enrolled 1026 participants to our substudy, who were then randomly assigned to either immediate (n=518) or deferred (n=508) ART. Median baseline characteristics included age 36 years (IQR 30-44), CD4 T-cell count 648 per µL (583-767), and HIV plasma viral load 4·2 log10 copies per mL (3·5-4·7). 29% were female and 28% were current smokers. Median follow-up time was 2·0 years (IQR 1·9-3·0). We noted no differences in FEV1 slopes between the immediate and deferred ART groups either in smokers (difference of -3·3 mL/year, 95% CI -38·8 to 32·2; p=0·86) or in non-smokers (difference of -5·6 mL/year, -29·4 to 18·3; p=0·65) or in pooled analyses adjusted for smoking status at each study visit (difference of -5·2 mL/year, -25·1 to 14·6; p=0·61). INTERPRETATION: The timing of ART initiation has no major short-term effect on rate of lung function decline in HIV-positive individuals who are naive to ART, with CD4 T-cell counts of more than 500 per µL. In light of updated WHO recommendations that all HIV-positive individuals should be treated with ART, regardless of their CD4 T-cell count, our results suggest an absence of significant pulmonary harm with such an approach. FUNDING: US National Heart Lung and Blood Institute, US National Institute of Allergy and Infectious Diseases, Division of AIDS, Agence Nationale de Recherches sur le SIDA et les Hipatites Virales (France), Australian National Health and Medical Research Council, Danish National Research Foundation, European AIDS Treatment Network, German Ministry of Education and Research, UK Medical Research Council and National Institute for Health Research, and US Veterans Health Administration Office of Research and Development.

International AIDS Society global scientific strategy: towards an HIV cure 2016.

Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.

Progress towards an HIV cure: update from the 2014 International AIDS Society Symposium.

Biomedical research has led to profound advances in the treatment of HIV infection. Combination antiretroviral therapy (ART) now provides the means to readily control viral infection, and people living with HIV who receive timely and effective ART can expect to benefit from a life expectancy comparable to uninfected individuals. Nevertheless, despite effective treatment, ART does not fully restore the immune system and importantly HIV persists indefinitely in latent reservoirs, resulting in the need for life-long treatment. The challenges and limits of life-long treatment have spurred significant scientific interest and global investment into research towards an HIV cure. The International AIDS Society (IAS) 2014 Towards an HIV cure symposium brought together researchers and community to discuss the most recent advances in our understanding of latency and HIV reservoirs, and the clinical approaches towards an HIV cure under current investigation. This report summarizes and reviews some of the major findings discussed during the symposium.

HIV test: which is your best? A National survey on testing preferences among MSM in Italy.

INTRODUCTION: HIV testing opportunities in Italy are frequently limited to the hospital setting. Experiences in other countries show that offering HIV testing in other facilities could improve HIV testing uptake. METHODS: An internet-based survey was conducted between March 10 and April 3, 2014. RESULTS: A total number of 348 questionnaires were collected. Responders were 88% male. Most represented age groups were 25-34 (35%) and 35-44 (25%). Most of the responders identify themselves as homosexual (81%) or bisexual (9%). Half of responders had an HIV test within 2 years (56%) while 18% never tested for HIV. Among all responders, 61% had more than 2 sexual partners in the past year. Reported condom use in the past year was: always 39%, always but once 11%, sometimes 27%, never 14%. Most known places to have an HIV test is the hospital (95%), STI clinic (58%) and chemical analysis laboratory (54%); most used places are hospital (73%), STI clinic (30%), laboratory (22%) while 5 responders reported having had a self-test at home. Preferred places where to have an HIV test is self-testing at home (53%), hospital (36%), pharmacy (32%) and headquarter of an organization (31%). Most known testing method is draw blood from vein (97%), which is also most used (80%) but the least preferred (31%) while saliva (65%) and finger prick (56%) are the preferred choices. Most responders know that physicians (84%) and nurses (77%) are those who perform HIV tests and most of them had an HIV test with them (60% and 65% respectively). Physicians are the preferred operators (54%) followed by self-testing (46%), nurses (46%) and peer-volunteers (39%). The ideal HIV test should be: reliable (86%), with no medical prescription (75%), free (63%), rapid (55%), with no personal information collected (45%), with the opportunity to speak with a peer-counsellor (36%). CONCLUSIONS: Changing HIV testing policies in Italy is urgently needed in order to grant a better access to the service: waiting for the results and bureaucratic obligations represent the major barriers to be removed. Home-testing and community-based testing seem to be among the best ways to offer new opportunities though they may require a change in the legal, social and cultural context to be implemented and home testing will not allow any kind of support for newly diagnosed people.