Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV.
Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA.
Retinoic acid (RA) is the most active metabolic product of Vitamin A. Appropriate levels of RA are required for proper embryonic development and tissue maintenance in all vertebrates. Inappropriate levels of RA in human embryos can cause congenital defects that affect many organs, including the heart and limbs, and lead to numerous types of cancers. Understanding how animals maintain appropriate RA levels and the consequences of inappropriate RA signaling will therefore provide insight into human congenital defects and diseases. RA signaling is mediated by RA receptors (RARs), which are transcription factors that are activated when binding RA. We have found that depletion of RARs in zebrafish results in defects that are surprisingly due to increases in embryonic RA and not a deficiency of RA signaling. Our results are the first to demonstrate that RAR depletion elicits a positive feedback mechanism that promotes RA signaling through complementary increases in both embryonic RA and RAR expression. Therefore, our analysis provides novel insight into the molecular mechanisms that are required to maintain appropriate RA signaling and will positively impact our understanding of the mechanisms underlying congenital defects.
The mechanism of CD4+ T-cell decline in HIV-1 infection is unclear, but the association with plasma viral RNA load suggests viral replication is involved. Indeed, viremic controller patients with low viral RNA loads typically maintain high CD4+ T-cell counts. Within a local cohort of 86 viremic controllers, we identify a subgroup (18 “discord controllers”) with low CD4+ T-cell counts that present clinical uncertainty. The underlying mechanism accounting for CD4+ T-cell decline in the face of low or undetectable plasma (RNA) viral load remains unresolved. The objective of this study was to investigate the viral and host immune system dynamics in discord controllers by measuring cellular HIV-1 DNA load, T-cell populations, and T-cell activation markers.
We compared discord controllers (viral RNA load <2000 copies/mL, <450 CD4+ T-cells/mm3) with typical controllers (viral RNA load <2000 copies/mL, >450 CD4+ T-cells/mm3) and progressors (viral RNA load >10,000 copies/mL, <450 CD4+ T-cells/mm3). We quantified CD4+/CD8+ naive/central memory/effector memory subsets (CD45RA/RO ± CD62L), activation levels (CD38+HLA-DR+), and HIV-1 DNA load.
Discord controllers resembled progressors showing high viral DNA load, depletion of naive CD4+ T-cells, and higher activation in all CD4+ T-cell subsets, compared with typical controllers. They were similar to typical controllers with lower CD8+ T-cell activation compared with progressors.
Our data are consistent with a relationship between CD4+ T-cell activation and disease progression. HIV-1 DNA load may be a better marker of viral replication and disease progression than viral RNA load. Lower level CD8+ T-cell activation correlates with low viral RNA load but not with disease progression or viral DNA load.
HIV-1; viremic controller; HIV-1 DNA; plasma RNA load; activation
Few studies have focused on language processing across modalities. Two experiments examined between-modality interactions across three prime–target intervals (0, 200, and 800 ms) in a cross-modal repetition priming paradigm. Event-related potentials were recorded to auditory targets following visual primes (Experiment 1) or visual targets following auditory primes (Experiment 2). In Experiment 1 robust repetition effects were found for auditory targets as early as 100 ms, and continued through the N400 epoch. Moreover, these visual–auditory repetition effects were large across all three prime–target intervals although they onset 200 ms later at the shortest interval. In Experiment 2 repetition effects to visual targets started later (at 200 ms), but also offset relatively later (∼1000 ms). These auditory–visual repetition effects were both smaller overall and absent for the two shortest prime–target intervals during the typical N400 window.
ERPs; N400; Repetition priming; Word recognition
In two experiments the effects of word repetition, synonymy, and coreference on event-related brain potentials during text processing were studied. Participants read one (Experiment 1) or two sentence (Experiment 2) texts in which critical nouns were preceded by the definite (the) or indefinite (a) articles. Experiment 1 was run as a control to verify that differences in article processing in the second sentences of Experiment 2 would not contaminate the ERPs to critical noun items. They did not. In Experiment 2, an initial sentence was used to set up a context and contained either a first presentation or synonym of the critical word from the second sentence. N400 (but not Late Positive Component; LPC) priming effects were found for repetitions and synonyms (larger for repetitions) in second sentences. This extends observations of priming in word lists and single sentences to two-sentence texts. There was also a greater left anterior negativity or “LAN” for coreferential critical nouns (those following the article “The”) compared to non-coreferential critical nouns (those following the article “A”) suggesting that ERPs are sensitive to working memory processes engaged during referential assignment. In response to the articles themselves, there was a greater N400-700 elicited by the article “A” vs. “The.” Finally, there was a greater N400-like negativity to the final words of non-coreferential sentences implying that the meanings of these sentences were difficult to integrate with the discourse level representation established by the prior sentence.
N400; LAN; ERPs; Coreference; Anaphoric processing; Sentence processing
Early detection of dysphagia is critical in stroke as it improves health care outcomes. Administering a swallowing screening tool (SST) in the emergency department (ED) appears most logical as it is the first point of patient contact. However, feasibility of an ED nurse-administered SST, particularly one involving trial water swallow administration, is unknown. The aims of this pilot study were to (1) implement an SST with a water swallow component in the ED and track nurses' adherence, (2) identify barriers and facilitators to administering the SST through interviews, and (3) develop and implement a process improvement plan to address barriers. Two hundred seventy-eight individuals with stroke symptoms were screened from October 2009 to June 2010. The percentage of patients screened increased from 22.6 in October 2009 to a high of 80.8 in March 2010, followed by a decrease to 61.9% in June (Cochran-Armitage test z = −5.1042, P < 0.0001). The odds of being screened were 4.0 times higher after implementation compared to two months before implementation. Results suggest that it is feasible for ED nurses to administer an SST with a water swallow component. Findings should facilitate improved quality of care for patients with suspected stroke and improve multidisciplinary collaboration in swallowing screening.
To describe predictors of pregnancy and changes in pregnancy incidence among HIV-positive women accessing HIV clinical care.
Data were obtained through the linkage of two separate studies; the UK Collaborative HIV Cohort study (UK CHIC), a cohort of adults attending 13 large HIV clinics, and the National Study of HIV in Pregnancy and Childhood (NSHPC), a national surveillance study of HIV-positive pregnant women. Pregnancy incidence was measured using the proportion of women in UK CHIC with a pregnancy reported to NSHPC. Generalised estimating equations were used to identify predictors of pregnancy and assess changes in pregnancy incidence in 2000-2009.
The number of women accessing care at UK CHIC sites increased as did the number of pregnancies (from 72 to 230). Older women were less likely to have a pregnancy (adjusted Relative Rate (aRR) 0.44 per 10 year increment in age [95% CI [0.41-0.46], p<0.001) as were women with CD4<200 cells/mm3 compared with CD4 200-350 cells/mm3 (aRR 0.65 [0.55-0.77] p<0.001) and women of white ethnicity compared with women of black-African ethnicity (aRR 0.67 [0.57-0.80], p<0.001). The likelihood that women had a pregnancy increased over the study period (aRR 1.05 [1.03-1.07], p<0.001). The rate of change did not significantly differ according to age group, ART use, CD4 group or ethnicity.
The pregnancy rate among women accessing HIV clinical care increased in 2000-2009. HIV-positive women with, or planning, a pregnancy require a high level of care and this is likely to continue and increase as more women of older age have pregnancies.
HIV; pregnancy; pregnancy rate; maternal age; highly active antiretroviral therapy; maternal-fetal infection transmission; United Kingdom
To describe antiretroviral therapy (ART) use and clinical status, at start of and during pregnancy, for HIV-positive women receiving ART at conception, including the proportion conceiving on drugs (efavirenz and didanosine) not recommended for use in early pregnancy.
Women with a pregnancy resulting in a live birth after 1995 (n=1,537) were identified in an observational cohort of patients receiving HIV care at 12 clinics in the UK by matching records with national pregnancy study data. Treatment and clinical data were analysed for 375 women conceiving on ART, including logistic regression to identify factors associated with changing regimen during pregnancy.
Of the 375 women on ART at conception, 39 (10%) conceived on dual therapy, 306 (82%) on triple therapy and 30 (8%) on >3 drugs. In total, 116 (31%) women conceived on a regimen containing efavirenz or didanosine (69 efavirenz, 54 didanosine, 7 both). Overall, 38% (143) switched regimen during pregnancy, of whom 41% (n=48) had a detectable viral load (≥50 copies/ml) around that time. Detectable viral load was associated with increased risk of regimen change (adjusted odds ratio 2.2, 95% confidence interval [1.3, 3.8]), while women on efavirenz at conception were three times more likely to switch than women on other drugs (3.3, [1.8, 6.0]). Regimen switching was also associated with calendar year at conception (0.9, [0.8-1.0]).
These findings reinforce the need for careful consideration of ART use among women planning or likely to have a pregnancy in order to reduce viral load before pregnancy and avoid drugs not recommended for early antenatal use.
HIV; pregnancy; antiretroviral agents; antiretroviral therapy; United Kingdom
The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone.
Women in UK CHIC receiving HIV-clinical care in 1996–2009, were found in the NSHPC dataset by initially ‘linking’ records with identical date-of-birth, linked records were then accepted as a genuine ‘match’, if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively).
Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.
Data linkage; HIV; Pregnant women; Antiretroviral therapy; Cohort analysis; United Kingdom
UK guidelines recommend routine HIV testing in healthcare settings if the local diagnosed HIV prevalence >2/1000 persons. This prospective study assessed the feasibility and acceptability, to patients and staff, of routinely offering HIV tests in four settings: Emergency Department, Acute Care Unit, Dermatology Outpatients and Primary Care. Modelling suggested the estimated prevalence of undiagnosed HIV infection in attendees would exceed 1/1000 persons. The prevalence identified prospectively was not a primary outcome.
Permanent staff completed questionnaires assessing attitudes towards routine HIV testing in their workplace before testing began. Subsequently, over a three-month period, patients aged 16–65 were offered an HIV test by study staff. Demographics, uptake, results, and departmental activity were collected. Subsets of patients completed questionnaires. Analyses were conducted to identify factors associated with test uptake.
Questionnaires were received from 144 staff. 96% supported the expansion of HIV testing, but only 54% stated that they would feel comfortable delivering testing themselves, with 72% identifying a need for training. Of 6194 patients offered a test, 4105 (66·8%) accepted (61·8–75·4% across sites). Eight individuals were diagnosed with HIV (0–10/1000 across sites) and all transferred to care. Younger people, and males, were more likely to accept an HIV test. No significant associations were found between uptake and ethnicity, or clinical site. Questionnaires were returned from 1003 patients. The offer of an HIV test was acceptable to 92%. Of respondents, individuals who had never tested for HIV before were more likely to accept a test, but no association was found between test uptake and sexual orientation.
HIV testing in these settings is acceptable, and operationally feasible. The strategy successfully identified, and transferred to care, HIV-positive individuals. However, if HIV testing is to be included as a routine part of patients’ care, additional staff training and infrastructural resources will be required.
The aim of this prospective study (20 months) was to assess HIV patients' use of Traditional, Complementary and Alternative Medicine (TCAM) and its effect on ARV adherence at three public hospitals in KwaZulu-Natal, South Africa. Seven hundred and thirty-five (29.8% male and 70.2% female) patients who consecutively attended three HIV clinics completed assessments prior to ARV initiation, 519 after 6 months, 557 after 12 and 499 after 20 months on antiretroviral therapy (ART). Results indicate that following initiation of ARV therapy the use of herbal therapies for HIV declined significantly from 36.6% prior to ARV therapy to 8.0% after 6 months, 4.1% after 12 months and 0.6% after 20 months on ARVs. Faith healing methods (including spiritual practices and prayer) declined from 35.8% to 22.1%, 20.8% and 15.5%, respectively. In contrast, the use of micronutrients (vitamins, etc.) significantly increased from 42.6% to 78.2%. The major herbal remedies that were used prior to ART were unnamed traditional medicine, followed by imbiza (Scilla natalensis planch), canova (immune booster), izifozonke (essential vitamins mixed with herbs), African potato (Hypoxis hemerocallidea), stametta (aloe mixed with vitamins and herbs) and ingwe (tonic). Herbal remedies were mainly used for pain relief, as immune booster and for stopping diarrhea. As herbal treatment for HIV was associated with reduced ARV adherence, patient's use of TCAM should be considered in ARV adherence management.
Traditional; complementary; alternative medicine; antiretroviral treatment adherence; prospective study; HIV patients; KwaZulu-Natal; South Africa
HIV and tuberculosis (TB) are commonly associated. Identifying latent and asymptomatic tuberculosis infection in HIV-positive patients is important in preventing death and morbidity associated with active TB.
Cross-sectional study of one time use of an interferon-gamma release assay (T-SPOT.TB - immunospot) to detect tuberculosis infection in patients in a UK inner city HIV clinic with a large sub-Saharan population.
542 patient samples from 520 patients who disclosed their symptoms of TB were tested. Median follow-up was 35 months (range 27-69). More than half (55%) originated from countries with medium or high tuberculosis burden and 57% were women. Antiretroviral therapy was used by 67%; median CD4 count at test was 458 cells/μl. A negative test was found in 452 samples and an indeterminate results in 40 (7.4%) but neither were associated with a low CD4 count. A positive test was found in 10% (50/502) individuals. All patients with positive tests were referred to the TB specialist, 47 (94%) had a chest radiograph and 46 (92%) attended the TB clinic. Two had culture-positive TB and a third individual with features of active TB was treated. 40 started and 38 completed preventive treatment. One patient who completed preventive treatment with isoniazid monotherapy subsequently developed isoniazid-resistant pulmonary tuberculosis. No patient with a negative test has developed TB.
We found an overall prevalence of latent TB infection of 10% through screening for TB in those with HIV infection and without symptoms, and a further 1% with active disease, a yield greater than typically found in contact tracing. Acceptability of preventive treatment was high with 85% of those with latent TB infection eventually completing their TB chemotherapy regimens. IGRA-based TB screening among HIV-infected individuals was feasible in the clinical setting and assisted with appropriate management (including preventive treatment and therapy for active disease). Follow-up of TB incidence in this group is needed to assess the long-term effects of preventive treatment.
Acute necrotizing encephalopathy (ANE) is a devastating and rapidly progressive neurologic disorder that occurs in healthy children after common viral infections. Typically, ANE is sporadic and does not recur. However, familial (ANE1) and recurrent cases have been reported and were recently linked to mutations in RANBP2 (RAN-binding protein 2). We report here a multiply affected kindred with recurrent familial ANE. These affected male siblings (a set of twins and their older brother) all presented with prodromal fever and upper respiratory tract infection that progressed within 72 hours to seizures, coma, and ultimately death, a course that is typical of ANE. It should be noted that 1 brother was treated with early aggressive management, including corticosteroids, and he survived for an additional 5 years. This represents the second reported case of familial ANE in the United States and the only case of male siblings with consanguineous parents. We hope that early recognition and growing awareness can lead to more effective treatment and better outcomes in the future. Pediatrics 2010;125: e693–e698
acute; recurrent; necrotizing; encephalopathy; ANE; genetic
Calculate time to first-line treatment failure, annual cost and
cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in
the UK, 1996–2006.
Population costs for HIV services are increasing in the UK and interventions
need to be effective and efficient to reduce or stabilize costs. 2NRTIs
+ NNRTI regimens are cost-effective regimens for first-line HAART, but
these regimens have not been compared with first-line PIboosted
Times to first-line treatment failure and annual costs were calculated for
first-line HAART regimens by CD4 count when starting HAART (2006 UK prices).
Cost-effectiveness of 2NRTIs+NNRTI versus
2NRTIs+PIboosted regimens was calculated for four CD4
55% of 5,541 people living with HIV (PLHIV) started HAART with CD4
count ≤200 cells/mm3, many of whom were Black Africans. Annual treatment
cost decreased as CD4 count increased; most marked differences were observed
between starting HAART with CD4 ≤200 cells/mm3 compared with CD4 count
>200 cells/mm3. 2NRTI+PIboosted and 2NRTI+NNRTI
regimens were the most effective regimens across the four CD4 strata;
2NRTI+NNRTI was cost-saving or cost-effective compared with 2NRTI
+ PIboosted regimens.
To ensure more effective and efficient provision of HIV services,
2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts
≤350 cell/mm3, unless specific contra-indications exist. This will
increase the number of PLHIV receiving HAART and will initially increase
population costs of providing HIV services. However, starting PLHIV earlier
on cost-effective regimens will maintain them in better health and use fewer
health or social services, thereby generating fewer treatment and care
costs, enabling them to remain socially and economically active members of
society. This does raise a number of ethical issues, which will have to be
acknowledged and addressed, especially in countries with limited
The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration.
Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake.
Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54).
This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.
pharmacokinetics; rifabutin; drug interactions
The number of people living with HIV (PLHIV) is increasing in the UK. This study estimated the annual population cost of providing HIV services in the UK, 1997–2006 and projected them 2007–2013.
Annual cost of HIV treatment for PLHIV by stage of HIV infection and type of ART was calculated (UK pounds, 2006 prices). Population costs were derived by multiplying the number of PLHIV by their annual cost for 1997–2006 and projected 2007–2013.
Average annual treatment costs across all stages of HIV infection ranged from £17,034 in 1997 to £18,087 in 2006 for PLHIV on mono-therapy and from £27,649 in 1997 to £32,322 in 2006 for those on quadruple-or-more ART. The number of PLHIV using NHS services rose from 16,075 to 52,083 in 2006 and was projected to increase to 78,370 by 2013. Annual population cost rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost between £721 and £758 million by 2013. When including community care costs, costs increased from £164 million in 1997, to £683 million in 2006 and between £1,019 and £1,065 million in 2013.
Increased number of PLHIV using NHS services resulted in rising UK population costs. Population costs are expected to continue to increase, partly due to PLHIV's longer survival on ART and the relative lack of success of HIV preventing programs. Where possible, the cost of HIV treatment and care needs to be reduced without reducing the quality of services, and prevention programs need to become more effective. While high income countries are struggling to meet these increasing costs, middle- and lower-income countries with larger epidemics are likely to find it even more difficult to meet these increasing demands, given that they have fewer resources.
Adherence to antiretroviral medication in the treatment of HIV is critical, both to maximize efficacy and to minimize the emergence of drug resistance. The aim of this prospective study in three public hospitals in KwaZulu-Natal, South Africa, is to assess the use of Traditional Complementary and Alternative Medicine (TCAM) by HIV patients and its effect on antiretroviral (ARV) adherence 6 months after initiating ARVs. 735 (29.8% male and 70.2% female) patients who consecutively attended three HIV clinics completed assessments prior to ARV initiation and 519 after six months on antiretroviral therapy (ART) Results indicate that the use of herbal therapies for HIV declined significantly from 36.6% prior to antiretroviral treatment (ART) initiation to 7.9% after being on ARVs for 6 months. Faith healing methods, including spiritual practices and prayer for HIV declined from 35.8% to 22.1% and physical/body-mind therapy (exercise and massage) declined from 5.0% to 1.9%. In contrast, the use of micronutrients (vitamins, etc.) significantly increased from 42.6% to 87.4%. In multivariate regression analyses, ARV non-adherence (dose, schedule and food) was associated with the use of herbal treatment, not taking micronutrients and the use of over-the-counter drugs. The use of TCAM declined after initiating ARVs. As herbal treatment for HIV was associated with reduced ARV adherence, patients' use of TCAM should be considered in ARV adherence management.
Traditional; complementary; alternative medicine; antiretroviral treatment adherence; HIV patients; KwaZulu-Natal; South Africa
Men who have sex with men (MSM) remain the group most at risk of acquiring HIV infection in Britain. HIV prevalence appears to vary widely between MSM from different ethnic minority groups in this country for reasons that are not fully understood. The aim of the MESH project was to examine in detail the sexual health of ethnic minority MSM living in Britain.
The main objectives of the MESH project were to explore among ethnic minority MSM living in Britain: (i) sexual risk behaviour and HIV prevalence; (ii) their experience of stigma and discrimination; (iii) disclosure of sexuality; (iv) use of, and satisfaction with sexual health services; (v) the extent to which sexual health services (for treatment and prevention) are aware of the needs of ethnic minority MSM.
The research was conducted between 2006 and 2008 in four national samples: (i) ethnic minority MSM living in Britain; (ii) a comparison group of white British MSM living in Britain; (iii) NHS sexual health clinic staff in 15 British towns and cities with significant ethnic minority communities and; (iv) sexual health promotion/HIV prevention service providers. We also recruited men from two "key migrant" groups living in Britain: MSM born in Central or Eastern Europe and MSM born in Central or South America.
Internet-based quantitative and qualitative research methods were used. Ethnic minority MSM were recruited through advertisements on websites, in community venues, via informal networks and in sexual health clinics. White and "key migrant" MSM were recruited mostly through Gaydar, one of the most popular dating sites used by gay men in Britain. MSM who agreed to take part completed a questionnaire online. Ethnic minority MSM who completed the online questionnaire were asked if they would be willing to take part in an online qualitative interview using email.
Service providers were identified through the British Association of Sexual Health and HIV (BASHH) and the Terrence Higgins Trust (THT) CHAPS partnerships. Staff who agreed to take part were asked to complete a questionnaire online.
The online survey was completed by 1241 ethnic minority MSM, 416 men born in South and Central America or Central and Eastern Europe, and 13,717 white British MSM; 67 ethnic minority MSM took part in the online qualitative interview. In addition 364 people working in sexual health clinics and 124 health promotion workers from around Britain completed an online questionnaire.
The findings from this study will improve our understanding of the sexual health and needs of ethnic minority MSM in Britain.
The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial–temporal lobe regions — two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal–prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.
White matter; Temporal lobe; Hippocampus; Orbitofrontal cortex
Previous magnetic resonance imaging (MRI) studies have reported various subtle brain abnormalities in schizophrenic patients, including temporal lobe abnormalities, which are of particular interest given the role of this brain region in auditory and language processing, and the characteristic deficits in these processes in schizophrenia. Subjects in this study were 16 male patients diagnosed with chronic schizophrenia and 15 healthy male comparison subjects. These patients were characterized by negative symptoms. High spatial resolution coronal MRI 1.5-mm-thick slices were used to measure the gray matter volume of the superior temporal gyrus, anterior and posterior amygdala/hippocampal complex, and parahippocampal gyrus. Patients, relative to normal comparison subjects, evinced a reduction of gray matter volume in bilateral superior temporal gyri and anterior amygdala/hippocampal complex. The reduction in gray matter of the superior temporal gyrus in patients with schizophrenia is consistent with previous findings, and is noteworthy in that it was found in this group of patients with predominantly negative symptoms. The reduction in the anterior amygdala/hippocampal complex was an additional temporal lobe finding. These results underscore the role of temporal lobe structures in the pathophysiology of schizophrenia.
Schizophrenia; Temporal lobe; Magnetic resonance imaging; Superior temporal gyrus; Amygdala; Hippocampus
Successful antiretroviral treatment is dependent on sustaining high rates of adherence. In the southern African context, only a handful of studies (both quantitative and qualitative) have looked at the determinants including a health behaviour theory of adherence to antiretroviral therapy. The aim of this study is to assess factors including the information, motivation and behavioural skills model (IMB) contributing to antiretroviral (ARV) adherence six months after commencing ARVs at three public hospitals in KwaZulu-Natal, South Africa.
Using systematic sampling, 735 HIV-positive patients were selected prior to commencing on ART from outpatient departments from three hospitals and followed-up at six months and interviewed with a questionnaire.
A good proportion of patients were found to be adherent using both adherence instruments (visual analog scale = VAS 82.9%; Adult AIDS Clinical Trials Group = AATCG 70.8%). After adjusting for significant socio-economic variables, both the VAS and the dose, schedule and food adherence indicator found levels of adherence amongst urban residents to be almost 3 times greater than that of rural residents. After adjusting for health-related variables, for both indicators better adherence was associated with low depression and poorer adherence was associated with poor environmental factors. Adjusted odds ratios for adherence when taking into account different behavioural variables were for both adherence indicators, discrimination experiences were associated with lower adherence, and higher scores in adherence information and behavioural skills were associated with higher adherence. For the VAS adherence indicator, higher social support scores were associated with higher adherence. For the dose, schedule and food adherence indicator, using herbal medicines for HIV was associated with lower adherence.
For the patients in this study, particularly those not living in urban areas, additional support may be needed to ensure patients are able to attend appointments or obtain their medications more easily. Adherence information and behavioural skills as part of the IMB model should be strengthened to improve adherence. Further psychological support is also required and patients' perceived need for ARTs should be routinely assessed.
To assess the use of opioids by primary care physicians for the treatment of chronic pain.
A written survey was completed by 248 primary care physicians. Outcomes of interest included type of opioids prescribed, common pain diagnoses treated, opioid prescribing concerns, treatment of patients with a history of substance use disorders and clinic-based protocols for pain management.
The mean age of the physicians who completed the questionnaire was 41 years. The majority were between the ages of 30 and 49 years (68%) with an equal number of men and women. Seventy percent were family physicians, 28.7% internists and less than 2% were community physicians and geriatricians. Physician concerns regarding opioid therapy included prescription drug abuse (84.2%), addiction (74.9%), adverse effects (68%), tolerance (60.7%), and medication interaction (32%). The survey found that the majority of the physicians were comfortable in prescribing narcotics to patients with terminal cancer. However, they were less comfortable prescribing narcotics to patients with low back pain and persons with a current or past history of drug or alcohol abuse. Physician management practices suggested that urine toxicology tests were under-utilized with only 6.9% reporting obtaining this test before prescribing opioids and only 15.0% performing urine toxicology tests on patients already prescribed opioids. Logistic regression analysis revealed that whether or not physicians routinely conducted urine toxicology screens was significantly (p = 0.015) predicted by whether they had a system to track patients on opioids when prescribing narcotics. The primary limitation of the study is the reliance on physician self-report rather than objective measures of physician behavior.
The survey suggests physicians are concerned about drug abuse, addiction, adverse effects, tolerance, and medication interaction. Their comfort level in prescribing opioids varies with the patient characteristics. Urine toxicology testing is underutilized in the primary care setting.
Chronic pain; Opioids; Track patients; Urine toxicology screen
To assess the use of opiods by primary care physicians for the treatment of chronic pain.
A written survey was completed by 248 primary care physicians. Outcomes of interest included type of opioids prescribed, common pain diagnoses treated, opioid prescribing concerns, treatment of patients with a history of a substance use disorders and clinic-based protocols for pain management.
The mean age of the physicians who completed the questionnaire was 41 years. The majority were between the ages of 30–49 (68%) with an equal number of men and women. Seventy percent were family physicians, 28.7% internists and less than 2% were community physicians and geriatricians. Physician concerns regarding opioid therapy included prescription drug abuse (84.2%), addiction (74.9%), adverse effects (68%), tolerance (60.7%), and medication interaction (32%). The survey found that the majority of the physicians were comfortable in prescribing narcotics to patients with the terminal cancer. However, they were less comfortable prescribing narcotics to patients with low back pain and persons with a past or current alcohol and drug abuse disorder. Physician management practices suggested that urine toxicology tests were under-utilized with only 6.9% reporting obtaining this test before prescribing opioids and only 15.0% performing urine toxicology tests on patients already prescribed opioids. Logistic regression analysis revealed that whether or not physicians routinely conducted urine toxiology screens was significantly (p 0.015) predicted by whether they had a system to track patients on opioids when prescribing narcotics. The primary limitation of the study is the reliance on physician self-report rather than objective measures of physician behavior.
The Survey suggests physicians are concerned about drug abuse, addiction, adverse effects, tolerance, and medication interaction. Their comfort level in prescribing opioids varies with the patient characteristics. Urine toxicology testing is underutilized in the primary care setting.
Chronic pain; opioids; urine toxicology screen; track patients
While men who have sex with men remain the group at greatest risk of acquiring HIV infection in the UK, the number of new diagnoses among heterosexuals has risen steadily over the last five years. In the UK, three-quarters of heterosexual men and women diagnosed with HIV in 2004 probably acquired their infection in Africa. This changing epidemiological pattern is particularly pronounced in East London because of its ethnically diverse population.
Design and methods
The objective of the study was to examine the social, economic and behavioural characteristics of patients with HIV infection currently receiving treatment and care in hospitals in East London. The research focused on ethnicity, gender, sexuality, education, employment, housing, HIV treatment, stigma, discrimination, religion, migration and sexual risk behaviour. People diagnosed with HIV infection attending outpatient treatment clinics at St Bartholomew's, the Royal London, Whipp's Cross, Homerton, Newham and Barking hospitals (all in East London) over a 4–6 month period were invited to participate in the study in 2004–2005. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire. During the study period, 2680 patients with HIV attended the outpatient clinics in the six participating hospitals, of whom 2299 were eligible for the study and 1687 completed a questionnaire. The response rate was 73% of eligible patients and 63% of all patients attending the clinics during the survey period.
A clinic-based study has allowed us to survey nearly 1700 patients with HIV from diverse backgrounds receiving treatment and care in East London. The data collected in this study will provide valuable information for the planning and delivery of appropriate clinical care, social support and health promotion for people living with HIV not only in East London but in other parts of the capital as well as elsewhere in the UK.
Objectives To estimate life expectancy for people with HIV undergoing treatment compared with life expectancy in the general population and to assess the impact on life expectancy of late treatment, defined as CD4 count <200 cells/mm3 at start of antiretroviral therapy.
Design Cohort study.
Setting Outpatient HIV clinics throughout the United Kingdom.
Population Adult patients from the UK Collaborative HIV Cohort (UK CHIC) Study with CD4 count ≤350 cells/mm3 at start of antiretroviral therapy in 1996-2008.
Main outcome measures Life expectancy at the exact age of 20 (the average additional years that will be lived by a person after age 20), according to the cross sectional age specific mortality rates during the study period.
Results 1248 of 17 661 eligible patients died during 91 203 person years’ follow-up. Life expectancy (standard error) at exact age 20 increased from 30.0 (1.2) to 45.8 (1.7) years from 1996-9 to 2006-8. Life expectancy was 39.5 (0.45) for male patients and 50.2 (0.45) years for female patients compared with 57.8 and 61.6 years for men and women in the general population (1996-2006). Starting antiretroviral therapy later than guidelines suggest resulted in up to 15 years’ loss of life: at age 20, life expectancy was 37.9 (1.3), 41.0 (2.2), and 53.4 (1.2) years in those starting antiretroviral therapy with CD4 count <100, 100-199, and 200-350 cells/mm3, respectively.
Conclusions Life expectancy in people treated for HIV infection has increased by over 15 years during 1996-2008, but is still about 13 years less than that of the UK population. The higher life expectancy in women is magnified in those with HIV. Earlier diagnosis and subsequent timely treatment with antiretroviral therapy might increase life expectancy.