HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy

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.

     

Oral candidiasis and seborrheic dermatitis in HIV-infected patients on highly active antiretroviral therapy

Background

Mucocutaneous manifestations such as oral candidiasis (OC) and seborrheic dermatitis (SD) are very common HIV‐related opportunistic events and are usually initial markers of immunodeficiency.

Aim

The purpose of this study was to evaluate the efficacy of highly active antiretroviral therapy (HAART) in the regression of HIV‐associated OC and SD.

Methods

In a prospective study, 120 HIV‐infected patients with OC and SD were divided into two groups: HAART‐treated patients (group 1, n=76) and non‐HAART‐treated patients (group 2, n=44). Non‐HAART‐treated patients were given antimicrobial therapy. Study subjects were matched for sex, age, risk, and stage of HIV infection. The results were analysed by χ² test and the Kaplan‐Meier method.

Results

At baseline, OC was evident in 59 (77.7%) of the HAART‐treated patients and in 34 (77.3%) of the non‐HAART‐treated patients, while SD was present in 19 (25.0%) of the HAART‐treated patients and in 17 (38.6%) of the non‐HAART‐treated patients. After a median follow‐up period of 22 months, regression of OC and SD occurred in 49 (83.1%) and 16 (84.2%) of the HAART‐treated patients, respectively. In the control group, regression of OC and SD occurred in only five (14.7%) and seven (41.2%) patients, respectively, during the same period.

Conclusions

HAART showed greater efficacy than standard antimicrobial therapy for the treatment of OC and SD in HIV‐infected patients.

     

The creation of a large UK-based multicentre cohort of HIV-infected individuals: The UK Collaborative HIV Cohort (UK CHIC) Study

Objectives

This paper describes the development of the UK Collaborative HIV Cohort (CHIC) Study. The aim of the study is to collate routinely collected data on HIV‐infected individuals attending one of seven clinical centres in the UK since 1 January 1996, with the objectives of describing changes over time in the frequency of AIDS‐defining illnesses, describing the uptake of and response to highly active antiretroviral therapy (HAART), and identifying factors associated with virological and immunological responses to HAART.

Methods

By December 2002, demographic, clinical and laboratory data had been collected on HIV‐positive patients seen at six of the seven HIV centres. Missing and inconsistent data had been investigated and the datasets audited. Records identified as relating to the same patient had been merged, and cross‐checks made with UK death registers to improve the accuracy of death reporting.

Results

The cohort currently contains information on 13 833 individuals. Eighty‐two per cent of the cohort are male, and the median age was 34 years at first follow‐up. The main risk factors for HIV infection have been determined as sex between men (63%) and sex between men and women (24%). Twenty‐five per cent of the cohort are known to have developed AIDS, and 8% have died.

Conclusions

The UK CHIC Study provides important information on the status of individuals infected with HIV in the UK, and provides a means to study the response to HAART and to monitor changes in the clinical event and death rates that have occurred since the introduction of HAART in the UK.

     

Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death

Objectives

The aim of the study was to compare incidence rates (IRs) of AIDS/death in patients with and without treatment interruption (TI) of combination antiretroviral therapy (cART) for periods of 3 months or more for different categories of CD4 cell count and viral load, and to determine risk factors for clinical progression to AIDS/death.

Methods

Patients starting cART with a CD4 cell count and a viral load available within 6 months of starting cART were included in the study. The IR and risk factors of TI were determined. We assessed the incidence rate ratios (IRRs) for TI and AIDS/death events using Poisson regression models.

Results

Of 3811 patients included in the study, 26% were ART‐naïve prior to cART. The median date of starting cART was July 1997, the median CD4 cell count was 226 cells/μL and the median viral load was 4.36 log₁₀ HIV‐1 RNA copies/mL. We observed 1243 interruptions and 403 AIDS‐events/deaths. The IR of AIDS/death was higher in patients with lower CD4 cell counts or higher viral loads, regardless of TI. After adjusting for baseline factors, the IR of AIDS/death was significantly higher in the TI group than in the non‐TI group [IRR 2.63; 95% confidence interval (CI) 2.01–3.44; P<0.0001]; this could be explained by current CD4 cell counts and viral loads, as the CD4 cell count‐ and viral load‐adjusted IRR was 1.14 (95% CI 0.86–1.51; P=0.37). Within the TI group, patients with a current CD4 cell count of <200 cells/μL had a 3‐fold higher risk of AIDS/death than those with a CD4 cell count of 200–350 cells/μL, whereas patients with a current CD4 cell count of >350 cells/μL had a 4‐fold lower risk of disease progression.

Conclusions

TI is common in clinical practice. The risk of AIDS/death increased more than 2‐fold for patients stopping all cART regimen drugs for 3 months or more. Among patients experiencing a TI, those with low CD4 cell counts, high viral loads or prior AIDS had an increased risk of AIDS/death. Hence, TI should be discouraged and closely monitored if it occurs.

     

Improved virological response to highly active antiretroviral therapy in HIV-1-infected patients carrying the CCR5 Delta32 deletion

Background

Patients heterozygous for the C‐C chemokine receptor 5 (CCR5) Δ32 deletion spontaneously progress less rapidly to AIDS and death than do wild‐type patients. We investigated whether the CCR5 Δ32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV‐1‐infected patients.

Patients and methods

We included in the study 565 HIV‐1‐infected patients from the French HIV‐1 infected cohort with documented date of serconversion (SEROCO)/haemophiliacs HIV‐1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection or a 2 log HIV‐1 RNA decrease) and at 12 months (defined as a plasma HIV‐1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan–Meier survival curves, with AIDS and death as outcomes.

Results

The Δ32 heterozygous patients (n=83; 15%) had a better virological response to HAART than wild‐type patients (73 vs 53% at 6 months, P=0.01; and 60 vs 44% at 12 months, P=0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild‐type patients in terms of survival and AIDS‐free survival.

Conclusions

CCR5 Δ32 heterozygous patients were more likely to have a virological response to HAART than wild‐type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long‐term impact of the Δ32 deletion on survival in HIV‐1‐infected treated patients should be investigated in a meta‐analysis.

     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

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.

     

The HLA–B*5703 allele confers susceptibility to the development of spondylarthropathies in Zambian human immunodeficiency virus–infected patients with slow progression to acquired immunodeficiency syndrome

Objective

To analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA).

Methods

A large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV‐1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV‐infected individuals without SpA and 43 healthy controls. Among all of the HIV‐1–infected patients, 25 SpA‐positive and 24 SpA‐negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA‐positive and 26 SpA‐negative patients were classified as rapid progressors. All patients were typed for HLA–B alleles.

Results

Of the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25).

Conclusion

HLA–B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.

     

Determinants of late HIV diagnosis among different transmission groups in Finland from 1985 to 2005

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.

     

Modelling the 3-year risk of myocardial infarction among participants in the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study

Objectives

To estimate the 3‐year risk of myocardial infarction (MI) among participants in the Data Collection on Adverse Events of Anti‐HIV Drugs (DAD) study.

Methods

Conventional cardiovascular risk equations were applied to baseline data from the DAD study to estimate the 3‐year risk of MI. Best estimates were obtained by simply applying the risk equations, with upper and lower limits based on worst case and optimistic case scenarios. Three‐year risks of AIDS or death were also estimated based on a prognostic scoring system for patients receiving antiretroviral (ARV) treatment, and on estimated AIDS rates in untreated people with HIV for those patients not on ARVs or if they were to cease ARVs.

Results

Analyses were based on 17 600 patients (24.3% female) recruited into the DAD study with baseline data and no previous MI. The overall 3‐year risk of MI was estimated to be 0.72% (lower limit 0.35, upper limit 1.12%), corresponding to a total predicted 127 (65–197) MIs over a 3‐year follow‐up period. The risk was much greater for men than women (0.92% vs. 0.07%), with only three (2–8) MIs predicted in women. The 3‐year risk of MI was estimated to increase from 0.30% (0.20–0.38%) in ARV naive patients to 1.07% (0.43–1.77%) in patients receiving ARVs from all three drug classes. The estimated 3‐year risk of AIDS or death was in the range 6.2% to 11.1% in patients receiving ARVs if they continued treatment, and 22.5% to 29.4% if they ceased ARVs.

Discussion

These models suggest that although the increase in relative risk of MI as a result of ARV treatment may be as high as threefold in a worst case scenario, the absolute risk is modest with a best estimate of 3‐year risk less than or equal to 1% in all groups of patients, and is outweighed by the benefits of ARV treatment in terms of reduced risk of AIDS and death in most patients. As estimates are based on models not validated for people receiving ARV drugs, all estimates should be interpreted cautiously.

     

Naively changing HAART

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.

     

Predictors of recent HIV testing in homosexual men in Australia

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.

     

CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL

Objective

To determine the prognostic value of baseline CD4 percentage in terms of patient survival in comparison to absolute CD4 cell counts for HIV‐positive patients initiating highly active antiretroviral therapy (HAART).

Methods

A population‐based cohort study of 1623 antiretroviral therapy‐naïve HIV‐positive individuals who initiated HAART between 1 August 1996 and 30 June 2002 was conducted. Cumulative mortality rates were estimated using Kaplan–Meier methods. Cox proportional hazards regression was used to model the effect of baseline CD4 strata and CD4 percentage strata and other prognostic variables on survival. A subgroup analysis was conducted on 417 AIDS‐free subjects with baseline CD4 counts between 200 and 350 cells/μL.

Results

In multivariate models, low CD4 percentages were associated with increased risk of death [CD4%<5, relative hazard (RH)=4.46; CD4% 5–14, RH=2.43; P<0.01 for both] when compared with those subjects with an initial CD4 fraction of 15% or greater, but had less predictive value than absolute CD4 counts. In subgroup analyses where absolute CD4 strata were not associated with mortality, a baseline CD4 fraction below 15% [RH=2.71; 95% confidence interval (CI) 1.20–6.10], poor adherence to therapy and baseline viral load >100 000 HIV‐1 RNA copies/mL were associated with an increased risk of death.

Conclusion

CD4 percentages below 15% are independent predictors of mortality in AIDS‐free patients starting HAART, including those with CD4 counts between 200 and 350 cells/μL. CD4 percentage should be considered for inclusion in guidelines used to determine when to start therapy.

     

Development and initial validation of a brief screener for focused HIV prevention efforts

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.

     

PENTA guidelines for the use of antiretroviral therapy in paediatric HIV infection. Pediatric European Network for Treatment of AIDS

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.

     

Quality of generalist vs. specialty care for people with HIV on antiretroviral treatment: a prospective cohort study

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.