The lived experience of major and treatment-resistant depression in England: a mixed-methods study.

INTRODUCTION: Major depressive disorder (MDD) is a common, frequently recurrent condition associated with decreased well-being and increased healthcare-related costs. Mixed-methods research provides multiple ways of illustrating the phenomenon to better understand patient experience, including where treatment is not working, referred to here as treatment-resistant depression (TRD). METHODS: A mixed-methods study investigated the experiences of people with symptomatic MDD, symptomatic TRD or TRD in remission, surveying 148 adults recruited from English clinical sites to measure symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5L/World Health Organisation Brief Assessment of QoL [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). Interviews with 26 survey respondents were analysed thematically. Integrated datasets explored areas of convergence and divergence, with concepts mapped against the EQ-5D-5L. RESULTS: Qualitative data explained low WHOQOL-BREF domain scores and the interrelation of psychological, emotional, cognitive and physical difficulties. Tiredness, lack of energy and motivation impacted daily activities, socialising and career goals. Low work performance scores were explained by poor concentration, decision-making and motivation. Participants also described the influence of social support and housing insecurity. Only 19 % of HRQoL qualitative codes mapped to the EQ-5D-5L. Themes dominant in patients with TRD were inability to cope, self-care challenges, dissatisfaction with mental health services and treatment pessimism. LIMITATIONS: Limited data collected on people with TRD in remission. CONCLUSIONS: The EQ-5D-5L and WPAI:D likely underestimate how depression impacts the HRQoL and work of people with MDD or TRD. Qualitative data suggest increased distress for people with TRD compared to those with MDD. Clinical management and treatment access decisions should consider the broader impacts of depression and environmental factors affecting the patient's experience.

Modelling the impact of CD4 testing on mortality from TB and cryptococcal meningitis among patients with advanced HIV disease in nine countries.

INTRODUCTION: Despite antiretroviral therapy (ART) scale-up among people living with HIV (PLHIV), those with advanced HIV disease (AHD) (defined in adults as CD4 count <200 cells/mm3 or clinical stage 3 or 4), remain at high risk of death from opportunistic infections. The shift from routine baseline CD4 testing towards viral load testing in conjunction with "Test and Treat" has limited AHD identification. METHODS: We used official estimates and existing epidemiological data to project deaths from tuberculosis (TB) and cryptococcal meningitis (CM) among PLHIV-initiating ART with CD4 <200 cells/mm3 , in the absence of select World Health Organization recommended diagnostic or therapeutic protocols for patients with AHD. We modelled the reduction in deaths, based on the performance of screening/diagnostic testing and the coverage and efficacy of treatment/preventive therapies for TB and CM. We compared projected TB and CM deaths in the first year of ART from 2019 to 2024, with and without CD4 testing. The analysis was performed for nine countries: South Africa, Kenya, Lesotho, Mozambique, Nigeria, Uganda, Zambia, Zimbabwe and the Democratic Republic of Congo. RESULTS: The effect of CD4 testing comes through increased identification of AHD and consequent eligibility for protocols for AHD prevention, diagnosis and management; algorithms for CD4 testing avert between 31% and 38% of deaths from TB and CM in the first year of ART. The number of CD4 tests required per death averted varies widely by country from approximately 101 for South Africa to 917 for Kenya. CONCLUSIONS: This analysis supports retaining baseline CD4 testing to avert deaths from TB and CM, the two most deadly opportunistic infections among patients with AHD. However, national programmes will need to weigh the cost of increasing CD4 access against other HIV-related priorities and allocate resources accordingly.

The impact of treatment-resistant depression on the lives of carers: A mixed-methods study.

INTRODUCTION: The lived experiences of informal carers of people with depression, particularly those with treatment-resistant depression (TRD), are rarely explored, despite their vital supportive role. METHODS: This mixed-methods study explored the quality of life (QoL) and experiences of carers of individuals with symptomatic TRD (Carers-Sym-TRD; n = 79) or in remission post-TRD (Carers-Rem-TRD; n = 20). Participating carers completed quantitative surveys measuring health-related and broader QoL (EQ-5D-5L/WHOQOL-BREF) and work productivity/activity impairment (WPAI:MM-CG). Interviews were also conducted with 12 Carers-Sym-TRD and 11 Carers-Rem-TRD and analysed thematically. RESULTS: Carers-Sym-TRD had impaired QoL compared with Carers-Rem-TRD, with significantly lower EQ-5D-5L index values (median = 0.84/1.00, respectively; p = 0.020) and WHOQOL-BREF overall score (median = 63.0/70.1; p < 0.001), physical health (median = 15.3/17.3; p < 0.001), psychological health (median = 13.3/14.7; p = 0.017), social relationships (median = 13.3/14.7; p = 0.017) and environment (median = 14.5/16.5; p = 0.011) domain scores. Work productivity/activity impairment was greatest in Carers-Sym-TRD across most WPAI:MM-CG domains, with a higher degree of impairment reported on the presenteeism and work productivity domains, however, there were no significant differences between the carer groups. Interview data suggested that impacts on carers' psychological/emotional wellbeing led to physical problems, which affected cognition and daily performance; Also, successful treatment for the person with depression helped carers worry less and reclaim their independence. LIMITATIONS: Recruitment challenges limited the Carers-Rem-TRD sample; clinical validation of the patient's depression diagnosis was not confirmed for all carers. CONCLUSIONS: TRD has an extensive adverse impact on carers' lives. Carers-Sym-TRD had significantly impaired QoL across a variety of domains compared with Carers-Rem-TRD, suggesting that achieving remission not only benefits patients but also those who care for them.

Health-related quality of life burden associated with treatment-resistant depression in UK patients: Quantitative results from a mixed-methods non-interventional study.

BACKGROUND: Major depressive disorder (MDD) and its more intractable variant, treatment-resistant depression (TRD), are common conditions that adversely affect patient well-being and health-related quality of life (HRQoL). This study aimed to quantify the impact of MDD and particularly TRD on the HRQoL, functioning and productivity of UK patients to support clinical and reimbursement decisions and policymaking. METHODS: 148 patients with clinician-verified symptomatic (non-treatment-resistant) MDD (Patients-MDD; n = 61) or TRD (Patients-TRD; n = 87) were recruited from ten clinical sites. Participants completed validated patient-reported outcome measures assessing depressive symptom severity (Patient Health Questionnaire-9 [PHQ-9]), HRQoL (EQ-5D-5 L/abbreviated World Health Organization Quality of Life Questionnaire [WHOQOL-BREF]) and work productivity/activity impairment (WPAI:D). RESULTS: Patients-TRD and Patients-MDD reported similar levels of depressive symptom severity (mean PHQ-9 16.2/16.6, respectively). However, HRQoL was significantly poorer for Patients-TRD compared with Patients-MDD, both in the overall cohort (median EQ-5D-5 L utility 0.606/0.721, respectively [p = 0.021]; WHOQOL-BREF overall score 55.2/58.8 [p = 0.024]) and in patients with a PHQ-9 score ≥15 (median EQ-5D-5 L utility 0.415/0.705, respectively [p<0.001]). Although a numerically lower proportion of Patients-TRD were employed (45% vs 57% of Patients-MDD; p = 0.204), employed Patients-MDD reported significantly higher absenteeism and work productivity loss. LIMITATIONS: A minority of patients screened as having symptomatic MDD or TRD self-reported low PHQ-9 symptom severity. This was addressed with a subgroup analysis of patients with more severe depression. CONCLUSIONS: TRD is associated with an added patient HRQoL burden, above that observed for non-treatment-resistant MDD. This highlights the unmet need for greater access to improved treatment, including new treatment options for Patients-TRD.

Community-based referral for tuberculosis preventive therapy is effective for treatment completion.

Expansion of tuberculous preventive therapy (TPT) is essential to curb TB incidence and mortality among people with HIV (PWH), yet implementation has been slow. Innovative strategies to operationalize TPT are urgently needed. Here we present an evaluation of community-based identification and referral of PWH on completion of a six-month course of isoniazid in a highly prevalent region in rural South Africa. Using a community-based TB/HIV intensive case finding strategy, a team of nurses and lay workers identified community members with HIV who were without fever, night sweats, weight loss, or cough and referred them to the government primary care clinics for daily oral isoniazid, the only available TPT regimen. We measured monthly adherence and six-month treatment completion in the community-based identification and referral (CBR) group compared to those already engaged in HIV care. Adherence was measured by self-report and urine isoniazid metabolite testing. A multivariable analysis was performed to identify independent predictors of TPT completion. Among 240 participants, 81.7% were female, median age 35 years (IQR 30-44), and 24.6% had previously been treated for TB. The median CD4 count in the CBR group was 457 (IQR 301-648), significantly higher than the clinic-based comparison group median CD4 of 344 (IQR 186-495, p<0.001). Independent predictors of treatment completion included being a woman (aOR 2.41, 95% 1.02-5.72) and community-based identification and referral for TPT (aOR 2.495, 95% 1.13-5.53). Among the CBR group, treatment completion was 90.0%, an absolute 10.8% higher than the clinic-based comparison group (79.2%, p = 0.02). Adherence was significantly greater in the CBR group than the clinic-based comparison group, as measured by self-report (p = 0.02) and urine isoniazid testing (p = 0.01). Among those not on ART at baseline, 10% of eligible PWH subsequently initiated ART. Community members living with HIV in TB endemic regions identified and referred for TPT demonstrated higher treatment completion and adherence compared to PWH engaged for TPT while receiving clinic-based care. Community-based identification and referral is an innovative adjunctive strategy to facilitate implementation of TB preventive therapy in people living with HIV.

Optimizing HIV Services for Key Populations in Public-Sector Clinics in Myanmar.

Key populations, ie, female sex workers, men who have sex with men, transgender people, people who inject drugs, and people in prisons and other closed settings, experience stigma, discrimination, and structural barriers when accessing HIV prevention and care. Public health facilities in Myanmar became increasingly involved in HIV service delivery, leading to an urgent need for healthcare workers to provide client-centred, key population-friendly services. Between July 2017-June 2018, the Myanmar Ministry of Health and Sports and National AIDS Programme collaborated with ICAP at Columbia University and the US Centers for Disease Control and Prevention to implement a quasi-experimental, multicomponent intervention including healthcare worker sensitization training with pre- and post- knowledge assessments, healthcare worker and client satisfaction surveys, and structural changes. We observed modest improvements among healthcare workers (n = 50) in knowledge assessments. Classification of clients into key population groups increased and fewer clients were classified as low risk. Key population clients reported favourable perceptions of the quality and confidentiality of care through self-administered surveys. Our findings suggest public health facilities can deliver HIV services that are valued by key population clients.

Current treatments used in clinical practice for major depressive disorder and treatment resistant depression in England: A retrospective database study.

BACKGROUND: Major depressive disorder (MDD) is a chronic recurrent or episodic psychiatric illness that can be successfully treated with oral antidepressants, yet one-in-three patients do not respond to currently-available treatments. According to the FDA and EMA, patients are considered to have treatment-resistant depression (TRD) when their MDD fails to respond adequately to ≥2 successive antidepressants in a single episode. AIMS: To describe current clinical management of patients with MDD and TRD in England, including treatment strategies and referral to secondary mental healthcare. METHOD: A retrospective cohort study of adult patients identified in primary care with diagnosed MDD, including a TRD subgroup (≥2 treatment failures as determined by treatment dynamics) was conducted using the Clinical Practice Research Datalink GOLD primary care database linked to Hospital Episode Statistics and Mental Health Services Data Set data (Protocol 19_019R). RESULTS: 41,375 patients with MDD (mean age 44yrs, 62% female, median follow-up 29mths); and 1,051 (3%) patients with TRD were identified. Mean time-to-TRD was 18 months. Most patients (>99%) received first-line antidepressant monotherapy. Following TRD criteria being met, antidepressant monotherapy use remained most frequent from TRD first-line (70%) to fifth-line (48%). Dual/triple antidepressant use remained constant (range:24%-26%), while augmented antidepressant use increased from TRD first-line (7%) to third-line (17%). Minimal non-pharmacological therapies were observed. CONCLUSIONS: Despite current clinical guidelines recommending a stepwise approach, many patients frequently cycle through numerous antidepressants with similar mechanisms of action and efficacy. These findings indicate a high unmet need for new treatments that improve outcomes in these patient populations.

Treatment Options for Dementia with Lewy Bodies: A Network Meta-Analysis of Randomised Control Trials.

INTRODUCTION: Dementia with Lewy bodies (DLB) is the third most common type of dementia after Alzheimer's disease (AD) and vascular dementia. Treatment is targeted at specific disease manifestations/symptoms. While donepezil is approved for the treatment of DLB in Japan, to date no other treatment has been approved for this indication anywhere in the world. Notwithstanding, many of the medications that are approved for AD are widely used in the treatment of DLB with varying degrees of success. Consequently, clinical evidence is limited, and there is a need to understand the comparative efficacy and safety of currently used therapies for DLB. The aim of this study was to conduct a network meta-analysis (NMA) to evaluate the outcomes of the available treatment options based on currently used trial endpoints. METHODS: Using data from a previously published systematic review, we conducted an NMA to investigate the efficacy and safety of treatments in patients with DLB. Networks were based on change from baseline of efficacy endpoints (Mini-Mental State Examination; Neuropsychiatric Inventory; Unified Parkinson's Disease Rating Scale) and rate of safety events (overall adverse events [AEs]; discontinuations; discontinuations due to AEs; psychiatric events). RESULTS: Focused around a common treatment option of placebo, the NMA comprised studies on donepezil, rivastigmine, memantine and quetiapine. Donepezil 3 mg, 5 mg and 10 mg doses were compared against each other and placebo. Overall, donepezil consistently performed better than the alternative treatments when compared to placebo for all efficacy and safety endpoints. However, the small sample size and/or heterogeneity of the studies led to uncertainty, resulting in no statistically significant differences favouring any treatment above another or placebo. CONCLUSION: Despite the lack of statistical significance, when assessing the efficacy and safety outcomes for each drug in the evidence network, donepezil appeared to have a more favourable overall benefit/risk profile for patients with DLB. Further comparative trials are required to improve understanding of the true difference between existing and potential future treatment options.

Improving estimates of district HIV prevalence and burden in South Africa using small area estimation techniques.

Many countries, including South Africa, have implemented population-based household surveys to estimate HIV prevalence and the burden of HIV infection. Most household HIV surveys are designed to provide reliable estimates down to only the first subnational geopolitical level which, in South Africa, is composed of nine provinces. However HIV prevalence estimates are needed down to at least the second subnational level in order to better target the delivery of HIV care, treatment and prevention services. The second subnational level in South Africa is composed of 52 districts. Achieving adequate precision at the second subnational level therefore requires either a substantial increase in survey sample size or use of model-based estimation capable of incorporating other pre-existing data. Our purpose is demonstration of the efficacy of relatively simple small-area estimation of HIV prevalence in the 52 districts of South Africa using data from the South African National HIV Prevalence, Incidence and Behavior Survey, 2012, district-level HIV prevalence estimates obtained from testing of pregnant women who attended antenatal care (ANC) clinics in 2012, and 2012 demographic data. The best-fitting model included only ANC prevalence and dependency ratio as out-of-survey predictors. Our key finding is that ANC prevalence was the superior auxiliary covariate, and provided substantially improved precision in many district-level estimates of HIV prevalence in the general population. Inclusion of a district-level spatial simultaneously autoregressive covariance structure did not result in improved estimation.

High prevalence of sexually transmitted infections among women screened for a contraceptive intravaginal ring study, Kisumu, Kenya, 2014.

We assessed prevalence and correlates of bacterial vaginosis (BV) and sexually transmitted infections (STIs) including herpes simplex virus type 2 (HSV-2), gonorrhoea (GC), syphilis (SYP), Chlamydia (CT) and HIV among Kenyan women aged 18­34 years who were screened for a contraceptive intravaginal ring study. Women provided demographic, behavioural and medical information, and underwent medical evaluation, including a pelvic exam. We computed crude and adjusted prevalence ratio (aPR) and 95% confidence interval (CI) using log-binomial regression. Of 463 women screened, 457 provided laboratory specimens and were included in the analysis. The median age was 25 years, interquartile range (21­28), and 68.5% had completed primary or lower education. Overall, 72.2% tested positive for any STI or BV. Point prevalence was 55.6, 38.5, 3.9, 2.0, 4.6, and 14.7% for HSV-2, BV, GC, SYP, CT, and HIV, respectively. Co-infection with HSV-2, BV, and HIV occurred in 28 (6.1%) participants. Having ≥1 STI/BV was associated with younger age at first sex (≤13 versus 17­19 years, aPR=1.27, 95% CI 1.07­1.51), history of exchange sex (aPR = 2.05, 95% CI 1.07­3.92), sexual intercourse in the past seven days (aPR = 1.17, 95% CI 1.01­1.36), and older age (30­34 versus 18­24 years, aPR = 1.26, 95% CI 1.06­1.48). STI/BV diagnosis was less likely for women reporting one lifetime sexual partner compared to women with ≥4 lifetime sexual partners (aPR = 0.70, 95% CI 0.54­0.92). Combination prevention approaches (biomedical, behavioural, social, and structural) tailored to women with diverse risk profiles may help mitigate STI/BV prevalence in this setting.

Higher specialty training in genitourinary medicine: A curriculum competencies-based approach.

Specialty trainees in genitourinary medicine (GUM) are required to attain competencies described in the GUM higher specialty training curriculum by the end of their training, but learning opportunities available may conflict with service delivery needs. In response to poor feedback on trainee satisfaction surveys, a four-year modular training programme was developed to achieve a curriculum competencies-based approach to training. We evaluated the clinical opportunities of the new programme to determine: (1) Whether opportunity cost of training to service delivery is justifiable; (2) Which competencies are inadequately addressed by direct clinical opportunities alone and (3) Trainee satisfaction. Local faculty and trainees assessed the 'usefulness' of the new modular programme to meet each curriculum competence. The annual General Medical Council (GMC) national training survey assessed trainee satisfaction. The clinical opportunities provided by the modular training programme were sufficiently useful for attaining many competencies. Trainee satisfaction as captured by the GMC survey improved from two reds pre- to nine greens post-intervention on a background of rising clinical activity in the department. The curriculum competencies-based approach to training offers an objective way to balance training with service provision and led to an improvement in GMC survey satisfaction.

Non-adherence among women enrolled in a contraceptive vaginal ring use study in Kisumu, Kenya, 2014-2015.

BACKGROUND: Given future potential use of vaginal rings to prevent HIV infection, we examined the association of contraceptive vaginal ring (CVR) non-adherence with user dissatisfaction, tolerability, demographic, and behavioral factors. METHODS: In an open-label single-group study, sexually active women aged 18-34 years using oral or injectable hormonal contraception, conveniently sampled from general population, were assigned to 6-month use of a commercial CVR currently not licensed for use in Kenya. Non-adherence in any CVR cycle completed was assessed from: (1) self-report (not used for at least 1 day), and (2) pharmacy record (failure to timely receive a new CVR or return a used one). Additionally, non-adherence was assessed in a subset of participants by residual progestin and estrogen levels measured in returned CVRs. RESULTS: Of 202 participants who underwent CVR insertion by a study clinician, 142 completed all 6 visits, 172 responded to questions about ring use, and 43 provided used CVRs from months 1, 3, and 6 for residual hormone analysis. Non-adherence was 14.0% (24/172) by self-report and 54.5% (110/202) by pharmacy record. Non-adherence by pharmacy record was significantly reduced among women with a salary-based income (prevalence ratio (PR) 0.71, 95% confidence interval (CI) (0.55-0.91)] compared to women with income not salary-based or no income. Participants dissatisfied with CVR on ≥4 aspects (ambiguity of instructions, inconvenience of use, sensation, sexual discomfort, etc.) were more likely to report non-adherence (PR 2.69, 95% CI=(1.31-5.52)] compared to those dissatisfied with ≤3 aspects. Non-adherence by residual hormone levels was identified in 46.5% (20/43) participants. Over time, this subset of participants showed increasing non-adherence (P=0.004). We found lack of agreement among the various measures of non-adherence. CONCLUSIONS: Economic empowerment interventions, especially those emphasizing partner-independent income options, and expanded education on CVR features may alleviate non-adherence. Addressing CVR dissatisfaction preemptively may also help mitigate non-adherence.

Effect of point-of-care CD4 cell count results on linkage to care and antiretroviral initiation during a home-based HIV testing campaign: a non-blinded, cluster-randomised trial.

BACKGROUND: HIV disease staging with referral laboratory-based CD4 cell count testing is a key barrier to the initiation of antiretroviral treatment (ART). Point-of-care CD4 cell counts can improve linkage to HIV care among people living with HIV, but its effect has not been assessed with a randomised controlled trial in the context of home-based HIV counselling and testing (HBCT). METHODS: We did a two-arm, cluster-randomised, controlled efficacy trial in two districts of western Kenya with ongoing HBCT. Housing compounds were randomly assigned (1:1) to point-of-care CD4 cell counts (366 compounds with 417 participants) or standard-of-care (318 compounds with 353 participants) CD4 cell counts done at one of three referral laboratories serving the study catchment area. In each compound, we enrolled people with HIV not engaged in care in the previous 6 months. All participants received post-test counselling and referral for HIV care. Point-of-care test participants received additional counselling on the result, including ART eligibility if CD4 was less than 350 cells per µL, the cutoff in Kenyan guidelines. Participants were interviewed 6 months after enrolment to ascertain whether they sought HIV care, verified through chart reviews at 23 local clinics. The prevalence of loss to follow-up at 6 months (LTFU) was listed as the main outcome in the study protocol. We analysed linkage to care at 6 months (defined as 1-LTFU) as the primary outcome. All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02515149. FINDINGS: We enrolled 770 participants between July 1, 2013, and Feb 28, 2014. 692 (90%) had verified linkage to care status and 78 (10%) were lost to follow-up. Of 371 participants in the point-of-care group, 215 (58%) had linked to care within 6 months versus 108 (34%) of 321 in the standard-of-care group (Cox proportional multivariable hazard ratio [HR] 2·14, 95% CI 1·67-2·74; log rank p<0·0001). INTERPRETATION: Point-of-care CD4 cell counts in a resource-limited HBCT setting doubled linkage to care and thereby improved ART initiation. Given the substantial economic and logistic hindrances to providing ART for all people with HIV in resource-limited settings in the near term, point of care CD4 cell counts might have a role in prioritising care and improving linkage to care. FUNDING: US Centers for Disease Control and Prevention.

Laboratory-based performance evaluation of PIMA CD4+ T-lymphocyte count point-of-care by lay-counselors in Kenya.

BACKGROUND: CD4+ T-lymphocyte count testing at the point-of-care (POC) may improve linkage to care of persons diagnosed with HIV-1 infection, but the accuracy of POC devices when operated by lay-counselors in the era of task-shifting is unknown. We examined the accuracy of Alere's Pima™ POC device on both capillary and venous blood when performed by lay-counselors and laboratory technicians. METHODS: In Phase I, we compared the perfomance of POC against FACSCalibur™ for 280 venous specimens by laboratory technicians. In Phase II we compared POC performance by lay-counselors versus laboratory technicians using 147 paired capillary and venous specimens, and compared these to FACSCalibur™. Statistical analyses included Bland-Altman analyses, concordance correlation coefficient, sensitivity, and specificity at treatment eligibility thresholds of 200, 350, and 500cells/µl. RESULTS: Phase I: POC sensitivity and specificity were 93.0% and 84.1% at 500cells/µl, respectively. Phase II: Good agreement was observed for venous POC results from both lay-counselors (concordance correlation coefficient (CCC)=0.873, bias -86.4cells/µl) and laboratory technicians (CCC=0.920, bias -65.7cells/µl). Capillary POC had good correlation: lay-counselors (CCC=0.902, bias -71.2cells/µl), laboratory technicians (CCC=0.918, bias -63.0cells/µl). Misclassification at the 500 cells/µl threshold for venous blood was 13.6% and 10.2% for lay-counselors and laboratory technicians and 12.2% for capillary blood in both groups. POC tended to under-classify the CD4 values with increasingly negative bias at higher CD4 values. CONCLUSIONS: Pima™ results were comparable to FACSCalibur™ for both venous and capillary specimens when operated by lay-counselors. POC CD4 testing has the potential to improve linkage to HIV care without burdening laboratory technicians in resource-limited settings.

Residual hormone levels in used contraceptive rings as a measurement of adherence to vaginal ring use.

OBJECTIVE: This study sought to measure residual contraceptive hormone levels in vaginal rings as an adherence marker for monitoring product use in clinical trials. STUDY DESIGN: Residual etonogestrel and ethinyl estradiol levels from used NuvaRings® of 26 self-reported adherent women enrolled in a clinical trial of vaginal ring acceptability were compared to those from 16 women who used NuvaRing® as their contraceptive choice. RESULTS: Twenty-one (81%) clinical trial rings had contraceptive hormone levels within the range of those used as a contraceptive choice. Five returned rings had unused or discordant levels of residual contraceptive hormones. CONCLUSION: Residual vaginal ring drug levels could help assess adherence in clinical trials.

Characteristics of women screened for a contraceptive intravaginal ring study in Kisumu, Kenya, 2014.

BACKGROUND: HIV antiretroviral-based intravaginal rings with and without co-formulated contraception hold promise for increasing HIV prevention options for women. Acceptance of and ability to correctly and consistently use this technology may create challenges for future ring-based microbicide trials in settings where this technology has not been introduced. We examined baseline factors associated with enrolling in a contraceptive intravaginal ring study in Kisumu, Kenya and describe notional acceptability (willingness to switch to a contraceptive ring based solely on information received about it). METHODS: Demographic, psychosocial, and behavioral eligibility screening of women 18-34 years was undertaken. Testing for pregnancy, HIV, and other sexually transmitted infections (STIs) was also conducted. We compared enrollment status across groups of categorical predictors using prevalence ratios (PR) and 95% confidence interval (CI) estimates obtained from a log-binomial regression model. RESULTS: Out of 692 women pre-screened April to November 2014, 463 completed screening, and 302 women were enrolled. Approximately 97% of pre-screened women were willing to switch from their current contraceptive method to use the intravaginal ring exclusively for the 6-month intervention period. Pregnancy, HIV, and STI prevalence were 1.7%, 14.5%, and 70.4% respectively for the 463 women screened. Women 18-24 (PR=1.47, CI 1.15-1.88) were more likely to be enrolled than those 30-34 years of age, as were married/cohabitating women (PR=1.62, CI 1.22-2.16) compared to those separated, divorced, or widowed. In adjusted analyses, sexual debut at less than 17 years of age, one lifetime sexual partner, abnormal vaginal bleeding in the past 12 months, condomless vaginal or anal sex in the past 3 months, and not having a sexual partner of unknown HIV status in the past 3 months were predictive of enrollment. CONCLUSION: High notional acceptability suggests feasibility for contraceptive intravaginal ring use. Factors associated with ring use initiation and 6-month use will need to be assessed.

Global policy review of antiretroviral therapy eligibility criteria for treatment and prevention of HIV and tuberculosis in adults, pregnant women, and serodiscordant couples.

OBJECTIVE: This article reviews the antiretroviral therapy (ART)initiation criteria from national treatment guidelines for 70 countries and determines the extent of consistency with the current World Health Organization (WHO) recommendations. METHODS: Published ART guidelines were collected from the Internet, databases, and WHO staff. ART eligibility criteria for asymptomatic people, pregnant women, people with HIV-associated tuberculosis, serodiscordant couples, injecting drug users, men who have sex with men, and sex workers were abstracted from them. Multiple regression analysis was used to determine the relation between ART eligibility criteria, ART coverage, and various population characteristics and policy interventions. RESULTS: Of the 70 countries, 42 (60%) follow WHO's ART guidelines for asymptomatic people and 31 (44%) for pregnant women,recommending ART at CD4 count of ≤350 cells/mm(3). Twenty-three(33%) countries recommend ART for people with HIV-associated tuberculosis irrespective of CD4 count. Nineteen countries are also recommending or considering earlier ART above CD4 count ≤350 cell/mm(3) for asymptomatic people, pregnant women, and/or serodiscordant couples. Multiple linear regression analysis shows that HIV prevalence, year of publication of guidelines, and HIV expenditure are significantly associated with published ART eligibility criteria. On average, the ART coverage is similar irrespective of published guidelines being consistent with the WHO recommendation(P , 0.53). CONCLUSIONS: Published guidelines from a significant number of countries are not following WHO recommendations. Although published guidelines may not reflect practice, it is important to adapt recommendations and services quickly to reflect the emerging science on the health and prevention benefits of earlier access to ART.

Renal impairment is associated with coronary heart disease in HIV-positive men.

BACKGROUND: Chronic kidney disease is a risk factor for coronary heart disease (CHD). The association between renal impairment and CHD in HIV-positive patients remains poorly described. OBJECTIVE: To describe the CHD incidence in a cohort of HIV-positive patients and to examine the relationship between reduced estimated glomerular filtration rate (eGFR) and incident CHD. METHODS: We studied 7,828 HIV-positive patients who were followed up at 3 South London clinics between January 2004 and December 2009. CHD events were identified from electronic records and through elevated troponin levels. Multivariate Poisson regression analysis was used to identify factors associated with CHD among HIV-positive men. RESULTS: The incidence of CHD among men was 1.2 (95% CI, 0.8-1.8) per 1,000 person-years of follow-up, with 28 patients (0.4%) having experienced 32 CHD events. In adjusted analyses, older age (incidence rate ratios [IRR], 2.81; 95% CI, 1.51-5.25) and hepatitis C virus (HCV) status (IRR, 3.94; 95% CI, 1.00-15.5) were significantly associated with CHD. Although eGFR as a continuous variable was not associated with CHD, an eGFR <75 mL/min remained associated with incident CHD (IRR, 4.30; 95% CI, 1.33-14.5) after adjustment for age. No association between CHD and abacavir exposure was observed (IRR, 0.94; 95% CI, 0.30-2.99). CONCLUSIONS: The incidence of CHD in this ethnically diverse cohort was low. Our data suggest that impaired renal function identifies patients at increased risk of CHD events in whom management of traditional CHD risk factors should be prioritized.