Associations with sub-optimal clinic attendance and reasons for missed appointments among heterosexual women and men living with HIV in London.

Poor engagement in HIV care is associated with poorer health outcomes and increased mortality. Our survey examined experiential and circumstantial factors associated with clinic attendance among women (n = 250) and men (n = 106) in London with heterosexually-acquired HIV. While no associations were found for women, among men, sub-optimal attendance was associated with insecure immigration status (25.6% vs. 1.8%), unstable housing (32.6% vs. 10.2%) and reported effect of HIV on daily activities (58.7% vs. 40.0%). Among women and men on ART, it was associated with missing doses of ART (OR = 2.96, 95% CI:1.74-5.02), less belief in the necessity of ART (OR = 0.56, 95% CI:0.35-0.90) and more concern about ART (OR = 3.63, 95% CI:1.45-9.09). Not wanting to think about being HIV positive was the top reason for ever missing clinic appointments. It is important to tackle stigma and the underlying social determinants of health to improve HIV prevention, and the health and well-being of people living with HIV.

The association between use of chemsex drugs and HIV clinic attendance among gay and bisexual men living with HIV in London.

OBJECTIVES: To investigate the association between chemsex drug use and HIV clinic attendance among gay and bisexual men in London. METHODS: A cross-sectional survey of adults (> 18 years) diagnosed with HIV for > 4 months, attending seven London HIV clinics (May 2014 to August 2015). Participants self-completed an anonymous questionnaire linked to clinical data. Sub-optimal clinic attenders had missed one or more HIV clinic appointments in the past year, or had a history of non-attendance for > 1 year. RESULTS: Over half (56%) of the 570 men who identified as gay or bisexual reported taking recreational drugs in the past 5 years and 71.5% of these men had used chemsex drugs in the past year. Among men reporting chemsex drug use (past year), 32.1% had injected any drugs in the past year. Sub-optimal clinic attenders were more likely than regular attenders to report chemsex drug use (past year; 46.9% vs. 33.2%, P = 0.001), injecting any drugs (past year; 17.1% vs. 8.9%, P = 0.011) and recreational drug use (past 5 years; 65.5% vs. 48.8%, P < 0.001). One in five sub-optimal attenders had missed an HIV clinic appointment because of taking recreational drugs (17.4% vs. 1.8%, P < 0.001). In multivariable logistic regression, chemsex drug use was significantly associated with sub-optimal clinic attendance (adjusted odds ratio = 1.71, 95% confidence interval: 1.10-2.65, P = 0.02). CONCLUSIONS: Our findings highlight the importance of systematic assessment of drug use and development of tools to aid routine assessment. We suggest that chemsex drug use should be addressed when developing interventions to improve engagement in HIV care among gay and bisexual men.

HIV self-testing intervention experiences and kit usability: results from a qualitative study among men who have sex with men in the SELPHI (Self-Testing Public Health Intervention) randomized controlled trial in England and Wales.

OBJECTIVES: SELPHI (HIV Self-Testing Public Health Intervention) is the largest randomized controlled trial (RCT) of HIV self-testing (HIVST) in a high-income setting to date, and has recruited 10 000 men who have sex with men (cis- and transgender) and transgender women who have sex with men. This qualitative substudy aimed to explore how those utilizing self-tests experience HIVST and the implications for further intervention development and scale-up. This is the first qualitative study in Europe investigating experiences of HIVST among intervention users, and the first globally examining the experience of using blood-based HIVST. METHODS: Thirty-seven cisgender MSM SELPHI participants from across England and Wales were purposively recruited to the substudy, in which semi-structured interviews were used to explore testing history, HIVST experiences and intervention preferences. Interviews were audio-recorded, transcribed and analysed through a framework analysis. RESULTS: Men accessed the intervention because HIVST reduced barriers related to convenience, stigma and privacy concerns. Emotional responses had direct links to acceptability. Supportive intervention components increased engagement with testing and addressed supportive concerns. HIVST facilitated more frequent testing, with the potential to reduce sexually transmitted infection (STI) screening frequency. Substudy participants with an HIV-positive result (n = 2) linked to care promptly and reported very high acceptability. Minor adverse outcomes (n = 2; relationship discord and fainting) did not reduce acceptability. Ease of use difficulties were with the lancet and the test processing stage. CONCLUSIONS: Intervention components shaped acceptability, particularly in relation to overcoming a perceived lack of support. The intervention was broadly acceptable and usable; participants expressed an unexpected degree of enthusiasm for HIVST, including those with HIV-positive results and individuals with minor adverse outcomes.

Development and application of a new measure of engagement in out-patient HIV care.

OBJECTIVES: Commonly used measures of engagement in HIV care do not take into account that the frequency of attendance is related to changes in treatment and health status. This study developed a new measure of engagement in care (EIC) incorporating clinical factors. METHODS: We conducted semi-structured interviews with eight HIV physicians to identify factors associated with the timing of patients' next scheduled appointments. These factors informed the development of an algorithm to classify each month of follow-up as "in care" (on or before the time of the next expected attendance) or "out of care" (after the time of the next expected attendance). The EIC algorithm was applied to data from the UK Collaborative HIV Cohort (UK CHIC) study, a large clinical cohort study. RESULTS: The interviews indicated that time to next appointment varied depending on psychosocial and physical comorbidities, and clinical factors (time since diagnosis, AIDS diagnosis, treatment status, CD4 count and viral load). The resulting EIC algorithm was applied to 44 432 patients; 83.9% of the 3 021 224 person-months were "in care". Greater EIC was independently associated with older age, white ethnicity, HIV acquisition through sex between men, current use of antiretroviral therapy (ART), a higher nadir CD4 count, later calendar year and being seen at the clinic for the first time within the last year. CONCLUSIONS: This algorithm describing engagement in HIV care incorporates a time-updated measure of patients' treatment and health status. It adds to the options available for measuring this key performance indicator.

Increased attendances of people of eastern European origin at sexual health services in London.

OBJECTIVE: To describe the service use of migrants from eight central and eastern European (CEE) countries at two central London genitourinary medicine (GUM) clinics before and after accession to the European Union on 1 May 2004. METHODS: KC60 data collected between 1 June 2001 and 30 April 2007. Data refer to new attendances and exclude those attending for follow-up appointments. RESULTS: 102,604 people attended the clinics at least once over the study period. Between May 2006 and 30 April 2007 individuals born in the eight CEE countries accounted for 7.9% of attendances among women and 2.5% of attendances made by men; the proportion increasing significantly over the 6-year study period (p<0.001). Syphilis was more likely in CEE men (age-adjusted odds ratio (OR) 2.98, 95% CI 1.07 to 8.29) and family planning services were more likely to be required for CEE women (23.9% vs 12.4%, age-adjusted OR 2.33, 95% CI 2.02 to 2.68, p<0.001), than for those born elsewhere. A larger proportion of men from CEE countries were recorded as homosexual or bisexual than men from other countries (38.3% vs 31.9%, p = 0.003). CONCLUSIONS: CEE migrants already have a substantial impact on GUM services in London. If attendance rates continue at the current level CEE women will soon account for over 10% of new attendances. Although the majority of CEE migrants are men, proportionately fewer CEE men accessed GUM services than women. Sexual and reproductive health services need to adapt quickly to meet the needs of this growing population.

Africans in London continue to present with advanced HIV disease in the era of highly active antiretroviral therapy.

Our findings show that despite the numerous advances in the management of HIV disease, this has not resulted in earlier presentation in Africans or non-Africans. African patients are still presenting with significantly more advanced disease than non-Africans, and are more likely to have AIDS at presentation in 1998-1999 than in 1982-1995. An urgent need exists to identify the factors associated with delayed presentation, both to optimize clinical outcomes and reduce the possibility of onward transmission.

The effect of cyclic AMP and cyclic GMP phosphodiesterase inhibitors on the superoxide burst of guinea-pig peritoneal macrophages.

1. The cyclic nucleotide phosphodiesterase (PDE) activity of guinea-pig peritoneal macrophages was partially characterized and the effects of selective and non-selective inhibitors of adenosine 3':5'-cyclic monophosphate (cyclic AMP PDE) and guanosine 3':5'-cyclic monophosphate (cyclic GMP PDE) phosphodiesterases on superoxide generation were investigated using peritoneal macrophages from horse-serum pretreated guinea-pigs. 2. The non-selective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX) and the PDE I/V selective inhibitor, zaprinast, inhibited spontaneous superoxide generation with IC50s of 30.7 +/- 11.3 microM and 145 +/- 17 microM respectively (n = 6 and 5). The concentration-response curves for the PDE IV selective inhibitors rolipram and Ro20-1724 were biphasic; mean maximum inhibitions were 56.9 +/- 5.9% and 66.8 +/- 10.5% respectively at 300 microM, but in 2 out of 6 (rolipram) and 2 out of 5 (Ro20-1724) experiments inhibition was < 50%. The PDE III inhibitor SK&F 94120 was without effect. Spontaneous superoxide generation was reduced 57 +/- 10% by 1 microM prostaglandin E2 (PGE2) and 62.6 +/- 3.76% by 1 microM salbutamol. 3. The increase in superoxide generation elicited by FMLP (10(-9)-10(-5)M) was unaffected by any of the PDE inhibitors studied. Inhibition of FMLP-stimulated superoxide generation by PGE2 was enhanced in the presence of 10 microM IBMX. 4. Macrophages were found to contain a predominantly membrane bound cyclic AMP PDE (90% of total activity) which was unaffected by cyclic GMP or calcium/calmodulin. The cyclic AMP PDE activity in the cytosolic fraction was enhanced in the presence of calcium/calmodulin. Selective inhibitors of PDE IV inhibited the particulate cyclic AMP PDE activity (IC50s rolipram 1.5 +/- 0.3 microM, Ro 20-17244.1 +/- 0.6 microm) as did the non-selective inhibitor IBMX (IC50 22 +/- 8 microM). The macrophage particulate PDE activity was resistant to inhibition by the PDE III inhibitor SK&F 94836 and the PDE I/V inhibitor, zaprinast. The cytosolic calcium/calmodulin stimulated cyclic AMP hydrolytic activity was inhibited by zaprinast (IC50 - calcium/calmodulin 123 +/- 39 microM; + calcium/calmodulin IC50 17.7 +/- 6.3 microM).5. The results indicate that guinea-pig peritoneal macrophages contain a type IV cyclic AMP PDE which is predominantly membrane associated and a predominantly cytosolic calcium/calmodulin stimulated cyclic AMP PDE. Functional studies suggest that both of these PDE activities contribute to cyclic AMP hydrolysis and regulation of superoxide generation in these cells. Inhibition of spontaneous superoxide generation, but not that stimulated by FMLP, suggests that the activity of PDE inhibitors is subject to functional antagonism but that this can be overcome by enhancing cyclic AMP formation.

Isoprenaline induction of cAMP-phosphodiesterase in guinea-pig macrophages occurs in the presence, but not in the absence, of the phosphodiesterase type IV inhibitor rolipram.

The long-term effects of incubating freshly isolated, elicited guinea-pig peritoneal macrophages with the beta-adrenoceptor agonist isoprenaline and the selective inhibitor of phosphodiesterase (PDE) IV rolipram, on adenosine-3',5'-cyclic phosphate (cAMP)-specific PDE IV activity have been investigated. The level of cAMP PDE activity in macrophages was unaffected by long-term exposure of cells to rolipram alone. In contrast, in the presence of isoprenaline (10 microM), a concentration-related (0.05.50 microM) increase in cAMP PDE activity was observed in the cytosolic and particulate fractions. Incubation with isoprenaline alone did not affect macrophage cAMP PDE. cAMP PDE activities in homogenates of control cells and macrophages treated with isoprenaline (10 microM) and rolipram (5 microM) (3-fold activation) were inhibited by the selective PDE IV inhibitor, rolipram, with similar potencies (IC50: 2.3 microM). The increase in cAMP PDE activity in response to rolipram and isoprenaline was completely blocked by cyclohexamide (10 micrograms/ml). Incubating macrophages for 10 min with rolipram increased cAMP accumulation in the presence, but not in the absence, of isoprenaline (10 microM) over the same concentration range that induction of cAMP PDE activity was observed. cAMP levels remained elevated for at least 1 hr. Isoprenaline (10 microM) alone induced a transient elevation in cAMP levels that peaked at 2 min and had returned to basal levels by 10 min. Protein kinase A activity (PKA) was increased almost 10-fold (at 10 min) by exposing cells to rolipram plus isoprenaline and remained elevated for at least 4 hr. Isoprenaline alone induced a small (2-fold) increase in PKA activity and rolipram alone was without effect.

Why the(y) wait? Key informant understandings of factors contributing to late presentation and poor utilization of HIV health and social care services by African migrants in Britain.

The majority of new HIV diagnoses in the UK occur in people with heterosexually acquired HIV infection, the majority of whom are migrant Africans. In the UK HIV positive Africans access HIV services at a later stage of disease than non-Africans (Burns et al., 2001; Sinka et al., 2003). Employing purposive sampling techniques, semi-structured interviews were conducted with key informants to identify the key issues affecting utilization of HIV services for Africans in Britain. Considerable agreement about the major issues influencing uptake of HIV services existed amongst the key informants. Respondents felt there was high HIV awareness but this did not translate into perception of individual risk. Home country experience and community mobilization was highly influential on HIV awareness, appreciation of risk, and attitudes to health services. Institutional barriers to care exist; these include lack of cultural understanding, lack of open access or community clinics, failure to integrate care with support organizations, and the inability of many General Practitioners to address HIV effectively. Community involvement should include input to ensure there is: better cultural understanding within the health care system; normalization of the HIV testing process; and a clear message on the effectiveness of therapy.

Diagnosis of bacterial vaginosis in a routine diagnostic laboratory.

Vaginal swabs from 299 hospital and general practitioners' patients were examined for Gardnerella vaginalis by Gram film and by culture, G. vaginalis was isolated in 12% of cultures. Comparison between the 'clue' cell and culture methods suggested that the former is a rapid, acceptable routine screening method for the detection of G. vaginalis. The value of the traditional method of identifying G. vaginalis by sensitivity testing is questioned. All specimens were also examined by Gram film and culture, for the presence of Mobiluncus spp, which was detected in 8.4% of specimens by Gram film but only 0.7% by culture. From a questionnaire returned by 84% of clinicians, metronidazole was found to be the most commonly used antimicrobial agent for the treatment of G. vaginalis, and in all but one case appeared to be clinically effective.