Preferences and Acceptability of Vaginal Delivery Forms for HIV Prevention Among Women, Male Partners and Key Informants in South Africa and Zimbabwe: Qualitative Findings.

The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.

Young Women's Ratings of Three Placebo Multipurpose Prevention Technologies for HIV and Pregnancy Prevention in a Randomized, Cross-Over Study in Kenya and South Africa.

End-user input is critical to inform development of multipurpose prevention technology (MPT) products that prevent HIV and pregnancy. The TRIO Study, conducted in Kenya and South Africa, enrolled 277 HIV-negative women aged 18-30 in a randomized cross-over study to use each placebo MPT (daily oral tablets, monthly injections, and monthly vaginal ring) for one month. At the end of each month, participants rated how much they liked using the product on a 5-point Likert scale (5 = liked very much). We compared mean ratings using paired t-tests and examined sociodemographic-, attribute-, and behavior-related characteristics associated with ratings using multivariable linear regression and data from in-depth interviews. After use, mean ratings were significantly higher for injections [4.3 (SD = 1.0)] compared with tablets [3.0 (SD = 1.3)] and rings [3.3 (SD = 1.4)] (p < 0.001); mean ratings for rings were significantly higher than for tablets (p = 0.013). Mean ratings of a hypothetical active MPT increased for all products after the one-month period of use, with the greatest increase for rings, the least familiar product. In multivariable analysis, acceptability of key product attributes (e.g., product look) were associated with a significant increase of ≥ 1 point in the mean rating across all three products (p ≤ 0.001). Perceived ability to use the product without partner knowledge was associated with a higher mean rating for rings (b = 0.50; p = 0.006). The acceptability of product attributes contributed significantly to the rating of all products, highlighting the value of choice in pregnancy and HIV prevention to accommodate diverse users.

End-Users' Product Preference Across Three Multipurpose Prevention Technology Delivery Forms: Baseline Results from Young Women in Kenya and South Africa.

A multipurpose prevention technology (MPT) that combines HIV and pregnancy prevention is a promising women's health intervention, particularly for young women. However, little is known about the drivers of acceptability and product choice for MPTs in this population. This paper explores approval ratings and stated choice across three different MPT delivery forms among potential end-users. The Trio Study was a mixed-methods study in women ages 18-30 that examined acceptability of three MPT delivery forms: oral tablets, injections, and vaginal ring. Approval ratings and stated choice among the products was collected at baseline. Factors influencing stated product choice were explored using multivariable multinomial logistic regression. The majority (62%) of women in Trio stated they would choose injections, 27% would choose tablets and 11% would choose the ring. Significant predictors of choice included past experience with similar contraceptive delivery forms, age, and citing frequency of use as important. Ring choice was higher for older (25-30) women than for younger (18-24) women (aRR = 3.1; p < 0.05). These results highlight the importance of familiarity in MPT product choice of potential for variations in MPT preference by age.

Association between Smoking and Uveitis: Results from the Pacific Ocular Inflammation Study.

PURPOSE: To assess whether cigarette smoking is associated with the development of uveitis in a population-based setting. DESIGN: Retrospective, population-based, case-control study. PARTICIPANTS: Patients aged ≥ 18 years who were seen at a Kaiser Permanente Hawaii clinic between January 1, 2006, and December 31, 2007. Analysis included 100 confirmed incident uveitis cases, 522 randomly selected controls from the general Kaiser Hawaii population, and 528 randomly selected controls from the Kaiser Hawaii ophthalmology clinic. METHODS: International Classification of Diseases, 9th revision (ICD-9), diagnosis codes were used to identify possible uveitis cases. A uveitis fellowship-trained ophthalmologist then conducted individual chart review to confirm case status. Multivariate logistic regression models were used to evaluate the association between smoking and uveitis, adjusting for age, sex, race, and socioeconomic status. MAIN OUTCOME MEASURES: Development of uveitis. RESULTS: Current smokers had a 1.63 (95% confidence interval [CI], 0.88-3.00; P = 0.12) and 2.33 (95% CI, 1.22-4.45; P = 0.01) times greater odds of developing uveitis compared with those who never smoked using the general and ophthalmology control groups, respectively. The association was even stronger with noninfectious uveitis, which yielded odds ratios of 2.10 (95% CI, 1.10-3.99; P = 0.02) and 2.96 (95% CI, 1.52-5.77; P = 0.001) using the general and ophthalmology control groups, respectively. CONCLUSIONS: Cigarette smoking is significantly associated with new-onset uveitis within a population-based setting. The association was stronger for noninfectious uveitis. Given the well-established risks of smoking with regard to other inflammatory disorders, these results reaffirm the importance of encouraging patients to avoid or cease smoking.

A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

OBJECTIVE: To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. DESIGN: Multicenter, block-randomized, observer-masked clinical trial. PARTICIPANTS: Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. INTERVENTION: Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. MAIN OUTCOME MEASURES: Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. RESULTS: Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). CONCLUSIONS: There was no statistically significant difference in corticosteroid-sparing control of inflammation between patients receiving methotrexate or mycophenolate mofetil. However, there was a 22% difference in treatment success favoring methotrexate.

Real World Outcomes in Patients With Metastatic, Castration-Resistant Prostate Cancer Treated With Radium-223 in Routine Clinical Practice in Sweden.

AIM: Estimate the effect of Radium-223 (Ra-223) on the incidence of bone fractures, prostate cancer death, and all-cause death compared with other standard treatments for metastatic, castration-resistant prostate cancer (mCRPC). METHODS: Using a cohort design, we estimated the effect of Ra-223 on the risk of bone fractures, all-cause and prostate cancer-specific mortality across different lines of treatment for mCRPC using Prostate Cancer data Base Sweden (2013-2018). The comparator group comprised other standard treatments for mCRPC. We used 36-month risk differences and hazard ratios (HRs) as effect estimates. RESULTS: The number of eligible individuals was 635, 453, 262, and 84 for the first-, second-, third-, and fourth-line cohorts, respectively. When compared Ra-223 to other standard treatments, the difference in the 36-month risk of fracture was 6% (95% confidence interval [CI], -7% to 18%) in the first-line cohort (n = 635) and 8% (95% CI, -7% to 18%) in the second-line cohort (n = 453). The number of fractures in the third-/fourth-line cohorts was too small for an adjusted comparison. The difference in 36-month mortality was higher in the first-line cohort 13% (95% CI, -3% to 31%), but lower in the second- and third-/fourth-line cohorts-8% (95% CI, -23% to 7%) and -14% (95% CI, -21% to 16%) respectively. Most deaths were due to prostate cancer. CONCLUSION: Results suggest that the difference in the risk of fractures is small, if any. A difference in the risk of mortality may be present in first-line treatment, but a decreased risk of mortality was observed in second and later lines of treatment. The results on mortality need to be considered in the context of potential unmeasured or residual confounding.

Young Women's Stated Preferences for Biomedical HIV Prevention: Results of a Discrete Choice Experiment in Kenya and South Africa.

BACKGROUND: Integrating end-user perspectives into the design of new biomedical HIV prevention products is recognized as vital to informing the product development pipeline. SETTING: Kisumu, Kenya; and Soshanguve, South Africa. METHODS: We conducted a discrete choice experiment survey with 536 women aged 18-30 years to assess preferences for hypothetical HIV prevention products characterized by the attributes of efficacy, pregnancy prevention, delivery form, dosing frequency, and side effects. Participants included product-experienced women from Tablet, Ring, Injection as Options TRIO, a cross-over clinical study evaluating 3 placebo delivery forms (oral tablets, vaginal rings, and injections), and a product-naive sample recruited from the same communities. Analyses used random parameters logit and latent class models. RESULTS: HIV prevention efficacy was a strong determinant of stated choice overall; however, in South Africa, delivery form was just as important, with an injection every 2-3 months most preferred and a daily oral tablet least preferred. In Kenya, product-experienced women preferred monthly injections and least preferred a monthly ring. Respondents indicated a preference for multipurpose prevention technologies that combine HIV and pregnancy protection. Latent class analyses confirmed these findings and delineated heterogeneity in preferences across subgroups defined by age, past experience with the delivery forms, and education. CONCLUSIONS: Despite an overall preference for products with high efficacy, we identified attributes salient to future uptake and use of HIV prevention products. Preferences for injectable products underscored interest in this pre-exposure prophylaxis delivery form. Likewise, the multipurpose prevention technology feature was valued in both Kenya and South Africa and most influenced interest in vaginal rings.

End-user preference for and choice of four vaginally delivered HIV prevention methods among young women in South Africa and Zimbabwe: the Quatro Clinical Crossover Study.

INTRODUCTION: Adherence to HIV prevention methods is a challenge, particularly for young women in Sub-Saharan Africa. End-user research during product development can inform modifiable factors to increase future uptake and adherence. METHODS: Preferences for four vaginally inserted placebo HIV prevention methods were assessed among Zimbabwean and South African young women using a crossover clinical design. For each of months 1 to 4, participants were asked to use a pre-coitally inserted film, insert (vaginal tablet) and gel once/week for a month, and a monthly ring in a randomly assigned sequence. Participants subsequently chose one preferred product to use as directed for the final study month. Women ranked the four products from most preferred to least preferred at enrolment and after trying all products. RESULTS: A total of 200 women aged 18 to 30 (mean 23) were enrolled; 178 (89%) completed follow-up. At baseline, 41% of participants selected the gel as their most preferred product and 61% selected the ring as least preferred. During the crossover period, most (82% to 85%) self-reported using each product at least once a week, although only half the time with sex. Objective biomarker data confirmed adequate use of all products. After trying each product, rankings changed with the film, ring, insert and gel being selected by 29%, 28%, 26% and 16% respectively. Choice varied significantly by country (p < 0.001): More Zimbabweans chose the film (45%), and more South Africans chose the insert (34%). Among women choosing the ring, 88% reported using it every time with sex. By contrast, self-reported adherence was lower for "on-demand" (coitally associated) products, with 40% to 55% using them every time during sex (p < 0.001). CONCLUSIONS: Preferences for these four dosage forms varied before and after use, and both within and across countries - there was no clear favourite - indicating the need for a range of options for end-users The ring's popularity increased the most with use, was the second most preferred delivery system, and per self-report, provided more coverage during sex. These end-user perspectives provide important information to product developers and funding agencies.

The Tablets, Ring, Injections as Options (TRIO) study: what young African women chose and used for future HIV and pregnancy prevention.

INTRODUCTION: Preventing HIV and unintended pregnancies are key global health priorities. To inform product rollout and to understand attributes of future multipurpose prevention technologies (MPT) associated with preference and use, we evaluated three placebo delivery forms: daily oral tablets, a monthly vaginal ring, and two monthly intramuscular injections in TRIO, a five-month study among young Kenyan and South African women. METHODS: HIV-negative, sexually active, non-pregnant women aged 18 to 30 were enrolled and randomized to use each placebo delivery form for one month (stage 1). Then, participants chose one product to use for two additional months (stage 2). We assessed safety, product ranking, choice, and use. We examined demographic and behavioural correlates of choice and, reciprocally, unwillingness to use in the future with logistic regression models. RESULTS: 277 women enrolled, 249 completed stage 1 and 246 completed stage 2. Median age was 23 years, 49% were Kenyan and 51% were South African. Three participants became pregnant during the study and one participant HIV-seroconverted. There were 18 product-related adverse events, six tablets-related, 11 ring-related, and one injection-related. After trying each product, 85% preferred a TRIO product over condoms. Injections were chosen most (64%, 95% confidence interval (CI) 58%, 70%; p < 0.001), and by more South Africans than Kenyans (odds ratio (OR) 2.01, 95% CI: 1.17, 3.43; p = 0.01). There was no significant difference in choosing tablets versus ring (21%, 95% CI: 16%, 26% vs. 15%, 95% CI: 11%, 20%; p = 0.11). Tablet and ring adherence, based on direct observations and self-reports, improved over time. However, participants' self-reported use of tablets did not match objective data from the electronic dose monitoring device. Participants were fully compliant with injections. CONCLUSION: In this population at risk for HIV and pregnancy, all participants agreed to choose and use a placebo MPT delivery form. A majority of participants preferred TRIO products to male condoms, an existing MPT. Injections were most liked and best used, however, they are years away from reaching the clinics. In the meantime, expanding the availability of tablets and giving access to rings can begin to fulfill the promise of choice for HIV prevention technologies and inform the development of suitable delivery forms as MPT.