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1.

Objectives

To study determinants of late HIV diagnosis in a low‐HIV‐prevalence (<0.1%) country where HIV spread among men who have sex with men (MSM) and heterosexuals in the 1980s, and among injecting drug users (IDUs) in the late 1990s.

Methods

Newly diagnosed HIV cases referred to the Helsinki University Central Hospital between 1985 and 2005 were reviewed to identify determinants of late HIV diagnosis, defined as diagnosis when the first CD4 count was <200 cells/μL, or when AIDS occurred within 3 months of HIV diagnosis. Determinants of late diagnosis were analysed using multivariate logistic regression.

Results

Among 934 HIV cases, 211 (23%) were diagnosed late. In the first 4‐year interval of each sub‐epidemic (1985–1989 for MSM and heterosexuals, 1998–2001 for IDUs), rates of late HIV diagnosis were 13%, 18% and 6%, respectively, but increased thereafter to 29%, 27% and 37%. Late diagnosis was associated with non‐Finnish ethnicity, older age, male gender, lack of earlier HIV testing, diagnosis at health care settings and later stage of the sub‐epidemic.

Conclusions

The lower rate of late diagnosis in the first 4‐year interval of each HIV sub‐epidemic suggests that the early stages of the HIV epidemic in Finland were detected early. This factor may have contributed to the low prevalence of HIV infection in Finland. The stage and age of the epidemic should be taken into account when interpreting the data on late HIV diagnosis, especially in cross‐country comparisons.
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2.
CC Lee  YJ Sun  T Barkham  YS Leo 《HIV medicine》2009,10(6):370-377

Objectives

The aim of the study was to elucidate primary drug resistance and transmission of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore.

Methods

Acute and recent HIV‐1 seroconverters were enrolled in the study. The HIV‐1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV‐1 transmission clusters were inferred from phylogenetic clustering analysis.

Results

Of the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV‐1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B′ (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty‐one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1.65–23.95]. MSM (OR 5.63, 95% CI 1.17–27.15), high viral load (OR 4.28, 95% CI 1.37–13.36) and young age (OR 0.92, 95% CI 0.85–0.99) were independently associated with clustered individuals.

Conclusions

In Singapore, HIV‐1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV‐1 transmission.
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3.

Background

Risk‐reduction counselling is a standard preventive intervention, but behaviour change is difficult to sustain over the duration of HIV infection. However, primary HIV infection (PHI) is highly infectious and plays a key role in transmission – especially through dense sexual networks – but is short term, so even transient risk reduction can mitigate its high infectivity. Targeting behaviour‐change interventions at recently infected individuals may be highly effective, particularly in higher risk groups. We explored the potential impact on HIV transmission‐risk behaviour of PHI diagnosis in men who have sex with men (MSM).

Methods

MSM with PHI were interviewed at diagnosis and after 3 months of follow‐up about their sexual behaviour in the 12‐week periods before and after diagnosis and standard counselling.

Results

A total of 98 of 104 eligible MSM (94%) participated in the study, with 100% follow‐up. PHI was associated with high levels of recreational drug use, low levels of condom use, high numbers of sexual partners and a history of sex work. In the 12 weeks post‐diagnosis, 76% of participants eliminated risk of onward transmission entirely and, overall, there was a significant reduction in transmission‐risk behaviour, with patients reporting greater condom use and fewer sexual partners. Those with continued transmission‐risk behaviour were more likely to have another sexually transmitted infection (STI), use ketamine and have more sexual partners at baseline.

Conclusions

Most MSM recently diagnosed with PHI changed their behaviour to substantially reduce the risk of onward HIV transmission. Strategies are needed to (a) increase diagnoses of PHI to target prevention efforts effectively and (b) further reduce risk behaviours by targeting enhanced counselling to those most likely to continue with risk behaviours.
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4.

Objectives

The aim of the study was to investigate the influence of continued injecting drug use, enrolment in an opiate substitution treatment programme (OSTP), or cessation of injecting drug use on the uptake and course of antiretroviral therapy (ART).

Design

A prospective observational study of all participants in the Swiss HIV Cohort Study followed between 1997 and 2006 was carried out.

Methods

We distinguished four groups of former or current injecting drug users (IDUs): (i) abstinent former IDUs; (ii) persons in OSTPs without concomitant injecting drug use; (iii) persons in OSTPs with concomitant injecting drug use; (vi) current IDUs. These groups were compared with a group of patients who had never been IDUs. Factors related to ART uptake and virological endpoints were analysed using logistic generalized estimating equations.

Results

We followed 8660 participants for 48 477 person‐years; 29.7% were in the IDU HIV transmission group. The likelihood of being on ART at biannual visits was lower among individuals in OSTPs with concomitant injecting drug use [odds ratio (OR) 0.79; 95% confidence interval (CI) 0.71–0.89] and current IDUs (OR 0.80; 95% CI 0.67–0.96), compared with those who had never been IDUs (reference), abstinent former IDUs (OR 1.13; 95% CI 1.02–1.25) and individuals in OSTPs without injecting drug use (OR 1.18; 95% CI 1.06–1.31). The likelihood of suppressed viral replication on ART was similar among those who had never been IDUs, abstinent former IDUs and individuals in an OSTP without injecting drug use, and lower among those in OSTPs with concomitant drug use (OR 0.82; 95% CI 0.72–0.93) and current IDUs (OR 0.81; 0.65–1.00). Adherence to ART was decreased among persons with continued injecting drug use, and correlated with virological outcome.

Conclusions

Uptake of and virological response to ART were improved among abstinent former IDUs and persons in OSTPs without concomitant injecting drug use, compared with persons with continued injecting drug use.
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5.

Objective

To produce European Guidelines for the use of antiretroviral therapy (ART) in HIV‐infected children.

Design

Systematic literature review using Medline, the major antiretroviral conference reports, and IDSA recommendations on guideline production.

Setting

Pediatric European Network for Treatment of AIDS (PENTA) Steering Committee.

Outcome measure

Guidelines have been produced for the use of antiretroviral therapy in HIV‐infected children in Europe. Recommendations on when to start ART and which ART to start, with dosages and a summary of the relevant literature, have been produced.

Conclusions

These guidelines are aimed at assisting paediatricians in Europe with ART prescribing, and provide a more cautious approach to starting therapy than current paediatric USA guidelines.
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6.
Predictors of recent HIV testing in homosexual men in Australia   总被引:1,自引:1,他引:1  

Objectives

To describe time trends and other predictors of recent HIV testing among homosexual men enrolled in behavioural surveillance studies in Australia.

Methods

Repeated cross‐sectional studies during the period 1996–2001 in Australian capital cities. Men were recruited from a variety of community‐based settings, including gay community outdoor events, sex on premises venues, and social venues. They underwent a brief self‐administered questionnaire in which they reported their HIV status, HIV‐testing history, sexual behaviour and demographic information.

Results

Questionnaires were returned for 22 161 HIV‐negative or status‐unknown participants. While 85.3% had ever tested for HIV, 57.6% had tested in the last 12 months. Recent testing was greater in those living in Sydney, in younger men, in gay‐identified men, in gay community‐attached men, in those who reported unprotected anal intercourse and a higher number of sexual partners, and in partners of HIV‐positive men. Although recent testing declined from 1996 to 2001, this trend was no longer significant when adjusted for other testing predictors.

Conclusions

In Australia, HIV testing among gay men decreased slightly from 1996 to 2001, but the trend was not significant when adjusted for other predictors. Testing levels were highest among those at highest risk of HIV infection, and lowest among non gay‐identified and non gay‐community attached homosexual men.
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7.

Objective

To assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care.

Methods

A nested matched case–control study of serodiscordant couples in which the HIV‐infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV‐1 RNA loads were measured at enrolment and longitudinally over 12 months of follow‐up. The study included 70 cases who seroconverted during study follow‐up and 167 matched controls who remained persistently serodiscordant.

Results

The incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person‐years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100 000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1–2.8], non‐disclosure of HIV status (OR: 5.5; 95% CI: 4.3–6.2) and not using condoms (OR: 2.8; 95% CI: 2.4–3.6).

Conclusions

Couples‐based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.
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8.

Objectives

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).

Methods

Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.

Results

Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.

Conclusions

Coinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.
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9.

Objective

To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV‐1 seroconversion.

Design

Data from HIV‐cohort studies where dates of seroconversion have been reliably estimated.

Methods

In previously untreated patients, short‐ and long‐term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow‐up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout.

Results

In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short‐term virological response (2.54 vs 2.13 log10 HIV‐1 RNA copies/mL at 1.5 months, P=0.03) and poorer long‐term immunological response (522 vs 631 cells/μL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/μL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/μL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long‐term virological response (0.67 log10 copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion.

Conclusion

Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow‐up carried out in high‐risk subgroups such as IDUs who have poorer responses.
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10.
11.

Objective

To determine the clinical course and optimum treatment of human immunodeficiency virus (HIV)–associated myositis.

Methods

Sixty‐four patients attending a county outpatient HIV/acquired immunodeficiency syndrome facility were referred for the presence of elevated creatine kinase (CK) levels or muscle weakness. Patients underwent neurologic and rheumatologic evaluation, electromyography, and muscle biopsy after exclusion for recreational drug or alcohol use, metabolic/endocrine disorders, zidovudine therapy, and other infections.

Results

Thirteen patients (20%) had biopsy‐proven myositis. The median duration of HIV infection prior to diagnosis of myositis was 4.3 years (range 0–11 years). Six patients had concomitant diffuse infiltrative lymphocytosis syndrome. There was no correlation of severity of weakness, stage of HIV infection, or retroviral treatment with the CK level at diagnosis. Eight patients received prednisone (60 mg/day) with 5 attaining complete resolution of myositis. The remaining 3 patients received immunosuppressive therapy (azathioprine or methotrexate and intravenous immunoglobulin) and had normalization of strength and CK. Four patients had spontaneous resolution of their myositis without treatment.

Conclusion

HIV‐associated myositis occurs at any stage of HIV infection, has a relatively good prognosis, responds well to immunosuppressive therapy, and has little evidence of adverse outcome on the HIV infection.
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12.

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.
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13.

Background

Few UK studies have systematically investigated which antiretroviral therapy (ART) combinations HIV‐infected people are commenced on, when they start and reasons for stopping or changing their regimens.

Objective

To describe when HIV‐infected ART‐naive patients started first‐, second‐ or third‐line triple ART, classes of drugs prescribed and whether stopping ART was associated with virological, immunological or clinical indicators of treatment failure.

Design

A multicentre prospective open cohort study, employing the National Prospective Monitoring System on the use, cost and outcome of HIV service provision in UK hospitals‐HIV Health‐economics Collaboration (NPMS‐HHC).

Setting

Five hundred and eighty‐five ART‐naive patients seen in one London and two non‐London HIV clinics between 1 January 1998 and 31 December 1999.

Results

Of 4044 HIV‐infected individuals seen, 585 (15%) were ART naive. Median time interval (interquartile range, IQR) between HIV diagnosis and starting triple ART was 800 (63–2094) days. Median CD4 count when first diagnosed with HIV infection was 278 (IQR 127–481) cells/µL which dropped to 190 (IQR 86–297) cells/µL when starting triple ART. Of these 585 patients, 162 started second‐line and 46 third‐line ART during the study period. Of those patients who stopped ART, 51% did not have evidence of virological, immunological or clinical indicators of therapy failure.

Conclusions

Reasons for the delay between diagnosis of HIV infection and starting ART are varied. The large proportion of individuals who stopped ART for reasons other than virological, immunological or clinical indicators of therapy failure, are most likely due to drug‐associated toxicity. Both of these findings need to be elucidated in greater detail through prospective studies.
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14.

Objective

To compare the direct costs of medical care in the year following HIV diagnosis for patients who present with a CD4 count<200 cells/μL (‘late presenters’) and those who present with a CD4 count >200 cells/μL (‘early presenters’).

Methods

Direct costs (i.e. drugs, laboratory tests, outpatient care, in‐patient care, and home care) for the 12 months following HIV diagnosis, sociodemographic data and clinical data were collected for all patients presenting for HIV care in Southern Alberta, Canada between April 1996 and April 2001. Mean costs are presented as costs in 2001 Canadian dollars.

Results

Thirty‐nine per cent of 241 patients presented with a CD4 count <200 cells/μL. The mean costs for late presenters were more than twice as high as those for early presenters (i.e. $18 448 vs. $8455, respectively). Late presenters were more likely to be older, male and black, and to have a risk activity of men having sex with men (MSM) or heterosexual contact (P<0.05). However, the large difference in mean costs cannot be attributed to differences in characteristics. When characteristics were statistically held constant, the estimated excess cost of late presentation was almost unaffected, at $9723 (z=5.6). Repeating the analysis using disaggregated costing categories suggested that the difference in total costs was largely attributable to differences in HIV‐related hospital care costs, which were 15 times higher for late presenters.

Conclusions

Direct care costs in the year following HIV diagnosis were more than 200% higher for patients who presented late. This difference could not be attributed to differences in patient characteristics. Most costs were attributable to HIV‐related hospital care costs and the immediate initiation of antiretroviral therapy. While early diagnosis in those at risk for HIV remains medically important, the short‐term economic impact is also substantial.
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15.

Objective

To investigate the impact of intermittent interleukin‐2 (IL‐2) plus combination antiretroviral therapy (cART) on HIV‐1 entry co‐receptor use.

Methods

Primary HIV‐1 isolates were obtained from 54 HIV‐1‐positive individuals at baseline and after 12 months using co‐cultivation of peripheral blood mononuclear cells (PBMC) with activated PBMC of HIV‐negative healthy donors. HIV‐1 co‐receptor use was determined on U87‐CD4 cells.

Results

Fourteen out of the 21 (67%) IL‐2‐treated individuals harbouring a primary CCR5‐dependent (R5) HIV‐1 isolate at baseline confirmed an R5 virus isolation after 12 months in contrast to 3 out of 7 (43%) of those receiving cART only. After 12 months, only 1 R5X4 HIV‐1 isolate was obtained from 21 cART+IL‐2‐treated individuals infected with an R5 virus at entry (5%) vs. 2/7 (29%) patients receiving cART alone, as confirmed by a 5‐year follow‐up on some individuals.

Conclusions

Intermittent IL‐2 administration plus cART may prevent evolution towards CXCR4 usage in individuals infected with R5 HIV‐1.
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16.

Objectives

The aim of the study was to explore the factors surrounding modification of the first antiretroviral (ARV) regimen where drug switch occurred 3 months or more after initiation. Reference was made to the British HIV Association (BHIVA) guidelines on HIV management.

Methods

A case note and questionnaire‐based audit was carried out.

Results

Toxicity was the single most important reason for ARV change and was the only, or a contributory, cause in over half the patients. Virological failure, adherence issues, requirement for treatment simplification, and patient request were other significant reasons cited. In one‐third of those with virological failure, six or more months had elapsed between first detection and the time of switching to a new ARV regimen.

Conclusions

This audit demonstrated broad adherence to the BHIVA guidelines, although the long time before switching ARVs in the setting of virological failure was of some concern, particularly given the continuing and significant occurrence of primary ARV resistance in the UK.
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17.

Objective

To determine if fat distribution is altered in HIV‐infected men without clinical evidence of lipodystrophy.

Methods

In a cross‐sectional design, 14 protease inhibitor (PI)‐treated men with lipodystrophy and 12 PI‐treated and five PI‐naive men without clinical evidence of lipodystrophy underwent body composition and fat distribution analysis by dual‐energy X‐ray absorptiometry and computed tomography. Their fat distribution was compared to 43 uninfected male controls matched for age and BMI.

Results

The percent of body fat in the trunk of men with HIV lipodystrophy was significantly greater compared to both HIV‐infected and healthy controls. The percentage of body fat in the extremities was significantly lower in men with HIV lipodystrophy compared to both HIV‐infected and healthy controls. HIV‐infected men without clinical evidence of lipodystrophy also had a significantly greater percentage of total body fat in the trunk and a significantly lower percent of body fat in the extremities compared to healthy controls. Among the HIV‐infected men, age was an independent predictor of truncal and extremity adiposity.

Conclusion

This study suggests that a continuum of change is present in the adipose organ of HIV‐infected men on antiretroviral therapy. Physical examination alone can miss significant changes in body fat distribution in HIV‐infected patients.
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18.

Objectives

The public health response to the spread of HIV relies on behavioural changes, especially reductions in sexual and drug‐use‐related transmission risk behaviours (TRBs). While understanding the factors that dispose people towards risky behaviours is important scientifically, it can be difficult to distil the many predictors of sexual risk behaviours into a useful clinical tool for focused prevention efforts. Our goal was to evaluate the extent to which known predictors of sexual TRBs (self‐efficacy, treatment optimism, engagement with medical care, awareness of risky behaviours, substance use, and relevant behavioural and socio‐demographic characteristics) combined with additional attitude‐related assessments to identify those who had engaged in recent sexual TRBs and may therefore be at risk of additional TRBs.

Methods

In this study, we analysed data on beliefs and behaviours related to sex, substance use, HIV prevention and other relevant factors for 280 patients at a publicly funded HIV/AIDS clinic in Seattle. All participants completed a baseline audio computer‐assisted self interview (ACASI) as part of a larger trial focused on reducing TRBs.

Results

Our multivariate model yielded three screening questions that could prove effective in identifying HIV‐positive patients in need of focused prevention resources.

Conclusions

The resulting screener holds promise as a brief and easily deployed tool that can be used by providers regardless of access to ACASI technology. Additional validation is needed and longitudinal evaluation is currently in progress.
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19.

Objectives

To describe health‐care use by persons with HIV in an urban area of Switzerland (Zurich). Further, to compare the different health‐care settings.

Design

A 1‐year prospective cohort study recruiting 60 patients at general practices and 60 patients at a specialized university outpatient clinic.

Methods

Patients and their treating physicians were interviewed or answered questionnaires, respectively, at baseline, month 6 and 12.

Results

During the study period, five patient groups were identified among the 106 enrolled patients, of whom (i) 42% saw a general practitioner exclusively, (ii) 31% were treated at the specialized outpatient clinic, (iii) 8% were in shared care, (iv) 10% changed health‐care model, and (v) 9% were lost to follow‐up. Baseline demographic, psychosocial and clinical data were similar among patient groups. At study end, the proportion of patients with HIV‐1 RNA < 400 copies/mL was 72%, 74%, 88%, 55% among groups (i) to (iv), respectively (ns), and 22% at month 6 among those lost to follow‐up. Indicators for quality of care were similarly good among all patient groups.

Conclusions

A well‐working system offers high‐quality healthcare to persons living with HIV, where existing teams of speciality and primary health‐care professionals efficiently and effectively co‐operate.
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20.
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