Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.

OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.

Investigating Conceptual Models for the Relationship Between Depression and Condomless Sex Among Gay, Bisexual, and Other Men Who have Sex with Men: Using Structural Equation Modelling to Assess Mediation.

The aim of this study is to investigate five hypothesized mechanisms of causation between depression and condomless sex with ≥ 2 partners (CLS2+) among gay, bisexual, and other men who have sex with men (GBMSM), involving alternative roles of self-efficacy for sexual safety and recreational drug use. Data were from the AURAH cross-sectional study of 1340 GBMSM attending genitourinary medicine clinics in England (2013-2014). Structural equation modelling (SEM) was used to investigate which conceptual model was more consistent with the data. Twelve percent of men reported depression (PHQ-9 ≥ 10) and 32% reported CLS2+ in the past 3 months. AURAH data were more consistent with the model in which depression was considered to lead to CLS2+ indirectly via low self-efficacy for sexual safety (indirect Beta = 0.158; p < 0.001) as well as indirectly via higher levels of recreational drug use (indirect Beta = 0.158; p < 0.001). SEM assists in understanding the relationship between depression and CLS among GBMSM.

Rapid initiation of antiretroviral therapy in those with newly diagnosed HIV infection in London, UK.

OBJECTIVES: In July 2016, as a result of patient demand, we introduced a rapid initiation option (RIO) to offer a first medical appointment and antiretroviral therapy (ART) initiation within 2 days of HIV diagnosis at 56 Dean Street (56DS) , a combined sexual health and HIV treatment service in London, UK. METHODS: We performed a retrospective case-note review of patients newly diagnosed with HIV infection at 56DS following the introduction of the new RIO from July to October 2016. In order to assess the effect of the new service on ART uptake, we chose a comparison group of newly diagnosed patients at 56DS from 1 year earlier: July to October 2015. RESULTS: In the 4 months following RIO introduction, there was a reduction in the median time from HIV diagnosis to the first medical appointment (7 versus 15 days; P < 0.00001) and to ART initiation (8 versus 21 days; P < 0.00001) compared with the same 4-month period 1 year previously. Uptake of ART at first appointment also significantly increased from 60% to 76% (P = 0.0074). CONCLUSIONS: By increasing our clinic capacity and awareness of staff and patients of the RIO service, we were able to fulfil the aim of the service to offer ART more quickly following HIV diagnosis.

InterPrEP: internet-based pre-exposure prophylaxis with generic tenofovir disoproxil fumarate/emtrictabine in London - analysis of pharmacokinetics, safety and outcomes.

OBJECTIVES: The National Health Service in England (NHS England) does not provide pre-exposure prophylaxis (PrEP) against HIV, forcing people to purchase generic versions on the internet. However, there are concerns about the authenticity of medicines purchased online. We established an innovative service offering plasma tenofovir (TFV) and emcitrabine (FTC) therapeutic drug monitoring for people buying generic PrEP online, to ensure that drug concentrations in vivo were consistent with those of propriety brands and previously published data. METHODS: TFV/FTC concentrations were measured by ultra-performance liquid chromatography ultraviolet detection. Evaluation of renal function and testing for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) were also carried out, at baseline and every 3-6 months, with risk reduction advice. RESULTS: A total of 293 individuals presented having purchased PrEP on the internet: 85% were white, 84% were taking daily PrEP, and 16% were event-driven. Most were on generic TFV disoproxil fumarate (TDF)/FTC from Cipla Ltd. Median (range) TFV and FTC plasma concentrations were 104 (21-597) ng/mL and 140 (17-1876) ng/mL, respectively. All concentrations were above our established plasma TFV and FTC targets, based on previously published data. Renal function was normal in all evaluable individuals and no new cases of HIV, HBV or HCV infection were seen. CONCLUSIONS: In a population at high risk of HIV acquisition, who cannot yet access PrEP on the NHS, concentrations of TFV and FTC in generic formulations purchased over the internet were similar to (or slightly higher than) those measured in phase I studies with the original formulation from Gilead (Truvada™), which has demonstrated high levels of protection against HIV infection in previous PrEP clinical trials.

Is PEP prescribed appropriately?

We describe the characteristics of HIV post-exposure prophylaxis (PEP) recipients and PEP indications at 56 Dean Street, a central London sexual health clinic. PEP was prescribed on 577 occasions. Most (97%) was given for unprotected anal intercourse. Over a fifth of exposures involved recreational drug use. Of the patients prescribed PEP, 5.9% were given PEP more than once in this period. As a snapshot of HIV risk behaviour, we note the prevalence of drug use, sex without condom use and group sex among PEP recipients.

Meeting complex needs: young people with HIV in London.

OBJECTIVES: The aim of the study was to examine the service use and characteristics of young people diagnosed with HIV infection aged under 25 years in order to design appropriate services. METHODS: A retrospective review of medical records of all individuals diagnosed as HIV positive aged under 25 years at Chelsea and Westminster Hospital, London, UK was carried out. The Health Protection Agency traced all individuals who had been lost to follow-up. We collected demographic, clinical, social and behavioural data. RESULTS: Of the 100 individuals diagnosed as HIV positive aged <25 years, 91% acquired HIV sexually; the median age at diagnosis was 21 years. Fifty-nine per cent were born outside the UK. Of 91 individuals diagnosed in the UK, 20% were diagnosed outside genitourinary medicine. Almost half had tested HIV negative a median of 13 months previously. At HIV diagnosis, 26% had a concurrent sexually transmitted infection; thereafter 34% had a documented risk of HIV transmission. The prevalence of psychiatric comorbidity was high (23%). Cervical screening rates were low; of nine women screened, five required treatment for cervical or vulval neoplasia. One fifth of the cohort were lost to follow-up a median 6 months from diagnosis. CONCLUSIONS: Young people with sexually acquired HIV infection have complex medical and psychosocial needs and many disengage from health services. Current services are not meeting the needs of these young people. Specialist young people's clinics may improve standards of care for this vulnerable group.

Religion and HIV diagnosis among Africans living in London.

OBJECTIVES: The aim of the paper was to describe the association of religion with HIV outcomes in newly diagnosed Africans living in London. METHODS: A survey of newly diagnosed HIV-positive Africans attending 15 HIV treatment centres across London was carried out between April 2004 and February 2006. Confidential self-completed questionnaires were used, linked to clinical records. Bivariate analyses were conducted to ascertain whether religious beliefs were associated with late diagnosis, antiretroviral therapy, and immunological and virological outcome 6 months post diagnosis. RESULTS: A total of 246 Black Africans were eligible and included in the analysis: 62.6% were women, and the median age was 34 years. The median CD4 count at diagnosis was 194 cells/µL (range 0-1334 cells/µL) and 75.6% presented late, as defined as a CD4 count < 350 cells/µL. Most participants were religious: non-Roman Catholic Christians (55.7%), Roman Catholics (35.2%) and Muslims (6.1%). Only 1.2% stated that they did not have a religion. Participants who attended religious services at least monthly were more likely to believe that 'faith alone can cure HIV' than those who attended less frequently (37.7% vs. 15.0%; P = 0.002). A small proportion (5.2%) believed that taking antiretroviral therapy implied a lack of faith in God. Bivariate analysis found no relationship between religiousness (as measured using frequency of attendance at religious services and religious attitudes or beliefs) and late diagnosis, changes in CD4 count/viral load 6 months post diagnosis, or initiation of antiretroviral therapy. CONCLUSIONS: Strong religious beliefs about faith and healing are unlikely to act as a barrier to accessing HIV testing or antiretroviral treatment for Black Africans living in London.

Menopause care in women living with HIV in the UK - A review.

Advances in HIV care over the last 30 years have transformed a virtually fatal condition into a chronic, manageable one. Antiretroviral therapy (ART) has dramatically changed the outlook for people living with HIV so that most individuals with well controlled disease have a normal life expectancy. As result of this increase in life expectancy, one-third of women living with HIV are of menopausal age. Adding to the shift in age distribution, rates of new HIV diagnosis are increasing in the over 50-year age group, likely the result of a combination of low condom use and perception of transmission risk and in women, an increased risk of HIV acquisition due to the mucosal disruption that accompanies vaginal atrophy. Many women living with HIV are unprepared for menopause, have a high prevalence of somatic, urogenital and psychological symptomatology and low rates of menopausal hormone therapy (MHT) use. Many women experience enormous frustration shuttling between their general practitioner and HIV care provider trying to have their needs met, as few HIV physicians have training in menopause medicine and primary care physicians are wary of managing women living with HIV, in part, because of fears about potential drug-drug interactions (DDIs) between MHT and ART. Several data gaps exist with regard to the relationship between HIV and the menopause, including whether the risk of HIV transmission is increased in virally-suppressed women with vaginal atrophy, whether or not menopause amplifies the effects of HIV on cardiovascular, psychological and bone health, as well as the safety and efficacy of MHT in women living with HIV. Menopausal women living with HIV deserve high quality individualised menopause care that is tailored to their needs. More research is needed in the field of HIV and menopause, primarily on cardiovascular disease and bone health outcomes as well as symptom control, and strategies to reduce HIV acquisition, encourage testing, and maintain older women in care in order to inform optimal clinical management.

Lights, camera research! Short film and social media to recruit to HIV research in Indonesia.

Introduction: HIV prevalence among men who have sex with men has increased in Indonesia, amid reports of growing stigma against lesbian, gay, bisexual and transgender individuals and policies that have pushed back public health outreach to these groups. Methods: We assessed the utility of tailored short film and targeted social media engagement to recruit men who have sex with men in Indonesia to HIV social science research. A short HIV testing promotion film, anonymised short survey and invite to a wider research study was embedded on a website platform and disseminated using geo and social/community group targeting for 1 month via a social networking app and social media platforms. Results: From 3 January 2021 to 3 February 2021, there were over 2200 hits of the website within Indonesia. A total of 177 male web users who identified as men who have sex with men or preferred not to declare their sexuality, engaged by watching the short film and completing the survey, they were aged between 17 and 60 years old, of Indonesian nationality and living in Indonesia. Of these, 88% indicated having at least one HIV test in their lifetime, 66% had felt shame with respect to their sexuality and 53% indicated feeling afraid to have a HIV test. Ninety (51%) of the 177 validated using their email or mobile phone number demonstrating willingness to be contacted to join a further study. Twenty-three eligible men who have sex with men, aged 21-55 years old, joined a further social science research study. Participants were from diverse backgrounds and included men born in provinces outside Bali, of different socio-economic and employment backgrounds and diverse relationship contexts. Discussion: Engaging, empowering digital media involving key health messaging can provide health education in more effective ways, build trust and bring communities together. Targeted digital and social media approaches could reach increasingly marginalised and vulnerable communities to promote individual and public health and enable recruitment to valuable medical research.

Interventions to increase access to STI services: a study of England's 'high-impact changes' across three central London clinics.

BACKGROUND: Increasing access to sexual health services is a key objective for the Department of Health in England and Wales. In 2006 it published 10 high-impact changes (HICs) designed to enhance 48 h access to genitourinary medicine services. However, there is limited evidence on the effectiveness of the proposed interventions. OBJECTIVE: To evaluate the implementation of five HICs in three sexual health clinics over 4 years. These HICs included a text message results service, nurse-delivered asymptomatic service, clinic refurbishment, a centralised booking service and an electronic appointment system. METHODS: The effect of HICs was evaluated by measuring clinical activity, number of sexual health screens performed, and patients seen within 48 h. These data were obtained from the clinic database, mandatory reports and Health Protection Agency waiting time surveys, respectively. RESULTS: The median number of new patients seen per month increased from 3635 to 4263 following the implementation of the five HICs. The follow-up/new patient ratio fell from 0.67 to 0.21 during the study. The biggest fall corresponded to a rise in patients receiving results by text message, from 0% to 40%. Only the centralised booking service was associated with a significant increase in the number of new patients seen. DISCUSSION: Providing results by text message was associated with a reduced number of follow-up patients, while implementation of a centralised booking service coincided with a significant increase in patient access. Further research is required to evaluate the relative importance of the other HICs.

Rectal chlamydia--a reservoir of undiagnosed infection in men who have sex with men.

OBJECTIVE: To determine the prevalence of rectal chlamydia infection in a cohort of men who have sex with men (MSM) and the proportion of infection that would be missed without routine screening. METHODS: MSM presenting to four HIV/GUM outpatient clinics at the Chelsea & Westminster Hospital NHS Foundation Trust between 1 November 2005 and 29 September 2006 were offered testing for rectal chlamydia infection in addition to their routine screen for sexually transmitted infections (STIs). Chlamydia trachomatis (CT) tests were performed using the Beckton-Dickinson Probe-Tec Strand Displacement Assay. Positive samples were re-tested at the Sexually Transmitted Bacteria Reference Laboratory, to confirm the result and identify lymphogranuloma venereum (LGV)-associated serovars. RESULTS: A total of 3076 men were screened. We found an 8.2% prevalence of infection with CT (LGV and non-LGV serovars) in the rectum and 5.4% in the urethra. The HIV and rectal chlamydia co-infection rate was 38.1%. The majority of rectal infections (69.2%, (171/247)) were asymptomatic and would have been missed if routine screening had not been undertaken. Of the samples re-tested, 94.2% (227/242) rectal and 91.8% (79/86) urethral specimens were confirmed CT positive and 36 cases of LGV were identified. CONCLUSION: Our data show a high rate of rectal chlamydia infection, in the majority of cases it was asymptomatic. We recommend routine screening for rectal chlamydia in men at risk, as this may represent an important reservoir for the onward transmission of infection.

Syphilitic periostitis in a newly diagnosed HIV-positive man.

A 36-year-old man presented for an HIV test, which answered positive. He gave a six-week history of headache and fever. His syphilis serology was also positive with a Venereal Disease Research Laboratory (VDRL) titre of 1:32, and positive Treponema pallidum particle agglutination (TPPA) assay and fluorescent treponemal antibody (FTA). When he attended for treatment of the syphilis, he had developed severe pain in both lower limbs. Plain radiographs were normal. An isotope bone scan showed multiple areas of increased uptake, consistent with syphilitic periostitis. Some of these lesions were asymptomatic. He was treated with benzathine penicillin and his pain resolved. The bone scan had normalized after six months. We review the previous literature regarding syphilitic bone pain and periostitis. We discuss the importance of considering syphilis in the differential diagnosis of any sexually active adult presenting with bone pain, and highlight the usefulness of isotope bone scans in clarifying the clinical picture.

Does dropping day 5 PEP follow-up affect outcomes? An audit of HIV post-exposure prophylaxis at a central London sexual health clinic.

UK post-exposure prophylaxis (PEP) guidelines were updated by the British Association for Sexual Health and HIV (BASHH) in 2011. In 2013, we changed policy to omit day 5 PEP follow-up at 56 Dean Street as it was felt clinically unnecessary. This audit compares our performance against BASHH standards for PEP attenders during June 2012 and June 2013. We identified 162 PEP prescriptions; PEP assessment and appropriate sexually transmitted infection testing was done well. PEP completion rates and post-PEP HIV testing were lower than BASHH standards. Following omission of day 5 review, documentation that results have been checked was poor; however, attendance at follow-up was not adversely affected.

Cessation of secondary prophylaxis in patients with cryptococcosis.

Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression. Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole. The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible. We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy.

Compound hygiene, presence of standpipe and the risk of childhood diarrhoea in an urban settlement of Papua New Guinea.

Children below five years of age residing in an urban settlement of Papua New Guinea were monitored from May 1987 to July 1988 in an attempt to identify aetiological factors of childhood diarrhoea. Presence of faeces in the compound was associated with a 48% increase (incidence density ratio (IDR) = 1.48, 95% confidence interval (CI): 1.163-1.897) in diarrhoea morbidity whilst the presence of pigs in the compound was associated with a 69% increase (IDR = 1.694, 95% CI:1.317-2.189). The presence of a standpipe in the compound was associated with a reduction in diarrhoea morbidity of 56%. The effect of presence of faeces, animals, and standpipe on the incidence of diarrhoea was not dependent on whether or not mothers were literate. We conclude that any intervention aimed at these factors is likely to reduce diarrhoea morbidity in similar urban ecosystems.

Snake bites by the Papuan taipan (Oxyuranus scutellatus canni): paralysis, hemostatic and electrocardiographic abnormalities, and effects of antivenom.

One hundred sixty-six patients with enzyme immunoassay-proven bites by taipans (Oxyuranus scutellatus canni) were studied in Port Moresby, Papua New Guinea. One hundred thirty-nine (84%) showed clinical evidence of envenoming: local signs were trivial, but most developed hemostatic disorders and neurotoxicity. The blood of 77% of the patients was incoagulable and 35% bled spontaneously, usually from the gums. Fifty-one per cent had microscopic hematuria. Neurotoxic signs (ptosis, ophthalmoplegia, bulbar paralysis, and peripheral muscular weakness) developed in 85%. Endotracheal intubation was required in 42% and mechanical ventilation in 37%. Electrocardiographic abnormalities (sinus bradycardia and septal T wave inversion) were found in 52% of a group of 69 unselected patients. Specific antivenom raised against Australian taipan venom was effective in stopping spontaneous systemic bleeding and restoring blood coagulability but, in most cases, it neither reversed nor prevented the evolution of paralysis even when given within a few hours of the bite. However, early antivenom treatment was associated statistically with decreased incidence and severity of neurotoxic signs. The low case fatality rate of 4.3% is attributable mainly to the use of mechanical ventilation, a technique rarely available in Papua New Guinea. Earlier use of increased doses of antivenoms of improved specificity might prove more effective.

Severe and complicated falciparum malaria in Melanesian adults in Papua New Guinea.

Severe falciparum malaria usually occurs in children, but also occurs in nonimmune migrants or partially immune adults in areas of unstable transmission. We have studied prospectively 70 adult patients with strictly defined severe malaria from the south coast of Papua New Guinea where malaria transmission is not intense. Only 19 (27.1%) were migrants from areas where malaria transmission does not occur; many other patients were periurban dwellers who had become infected after visits to their home villages. The most common clinical features were jaundice or hepatic dysfunction, impaired consciousness, renal failure, cerebral malaria, and anemia. Hypoglycemia was common following treatment with quinine. The overall case fatality rate was 18.6%; renal failure and cerebral malaria in particular were associated with a poor outcome. Reduction in mortality might be achieved by aggressive therapy of renal failure with earlier institution of dialysis; the use of preventive measures for immigrants or urban dwellers returning to high transmission areas might reduce the incidence of this dangerous disease.

Transient risk factors for acute childhood diarrhoea in an urban community of Papua New Guinea.

Transient risk factors may play an important role in the aetiology of acute diarrhoea. These factors have not been well elucidated. To assess them, we monitored 479 children below the age of 5 years living in a well-defined urban community in Port Moresby, Papua New Guinea, for one year, using the nested case-control method with density sampling. Comparing the odds ratios, we found that eating food that had been kept for more than 12 h, eating away from home, temporary absence of mother from home for more than one day, and the presence of respiratory infection in the child, were statistically associated with an increased risk of diarrhoea. We conclude that these transient factors must be addressed if effective control of diarrhoea is to be achieved. We believe that further studies will identify the factors more precisely and provide a better understanding of the method we have employed.