Safety, Adherence and Acceptability of Intermittent Tenofovir/Emtricitabine as HIV Pre-Exposure Prophylaxis (PrEP) among HIV-Uninfected Ugandan Volunteers Living in HIV-Serodiscordant Relationships: A Randomized, Clinical Trial

Background: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens. Design: Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment. Methods: Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT. Results: Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen. Conclusions: Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing. Registration Clinicaltrials.gov number NCT0093134

Willingness to pay for an mHealth anti-retroviral therapy adherence and information tool: Transitioning to sustainability, Call for life randomised study experience in Uganda.

Funder: Johnson & Johnson Corporate Citizenship TrustINTRODUCTION: Evidence shows benefit of digital technology for people living with human immunodeficiency virus on antiretroviral therapy adherence and retention in care, however, scalability and sustainability have scarcely been evaluated. We assessed participants' willingness to pay a fee for mHealth "Call for life Uganda" support, a mobile-phone based tool with the objective to assess sustainability and scalability. METHODS: "Call for Life study", approved by Makerere University, School of Public Health research & ethics committee, at 2 sites in Uganda, evaluated a MoTech based software "CONNECT FOR LIFE™" mHealth tool termed "Call for life Uganda". It provides short messages service or Interactive Voice Response functionalities, with a web-based interface, allows a computer to interact with humans through use of voice and tones input via keypad. Participants were randomized at 1:1 ratio to Standard of Care or standard of care plus Call for life Uganda. This sends pill reminders, visit reminders, voice messages and self-reported symptom support. At study visits 18 and 24 months, through mixed method approach we assessed mHealth sustainability and scalability. Participants were interviewed on desire to have or continue adherence support and willingness to pay a nominal fee for tool. We computed proportions willing to pay (± 95% confidence interval), stratified by study arm and predictors of willingness to continue and to pay using multivariate logistic regression model backed up by themes from qualitative interviews. RESULTS: 95% of participants were willing to continue using C4LU with 77.8% willing to pay for the service. Persons receiving care at the peri-urban clinic (OR 3.12, 95% CI 1.43-9.11.86) and those with exposure to the C4LU intervention (OR 4.2, 95% CI 1.55-11.84) were more likely to continue and pay for the service. Qualitative interviews revealed mixed feelings regarding amounts to pay, those willing to pay, argued that since they have been paying for personal phone calls/messages, they should not fail to pay for Call for life. CONCLUSIONS: Payment for the service offers opportunities to scale up and sustain mHealth interventions which may not be priorities for government funding. A co-pay model could be acceptable to PLHIV to access mHealth services in low resource settings. Clinical Trial Number NCT02953080

HIV Incidence and Risk Factors for Acquisition in HIV Discordant Couples in Masaka, Uganda: An HIV Vaccine Preparedness Study

To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1-6]; and 4.3 [2.8-6.4] and 4.4 [2.5-8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18-24 (aRR = 4.1, 95% CI 1.6-10.8) and 25-34 (aRR = 2.7, 95% CI 1.2-5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1-6); and reported genital discharge (aRR = 3.4, 95% CI 1.6-7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2-0.8); always (aRR = 0.1, 95% CI 0.02-0.9)]. In the follow-up risk analysis, young age [18-24 (aRR = 6.2, 95% CI 2.2-17.3) and 25-34 (aRR = 2.3, 95% CI 1.1-5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1-5.5), serological syphilis (aRR 3.2, 95% CI 1.3-7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4-16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population

CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa

BACKGROUND: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. METHODS AND FINDINGS: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. CONCLUSIONS: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa

Perceptions and Attitudes Toward an Interactive Voice Response Tool (Call for Life Uganda) Providing Adherence Support and Health Information to HIV-Positive Ugandans: Qualitative Study

BackgroundThe continuing decline in AIDS-related deaths in the African region is largely driven by the steady scale-up of antiretroviral therapy. However, there are challenges to retaining people living with HIV on treatment. Call for Life Uganda (CFLU) is an interactive voice response tool using simple analogue phones. CFLU supports patients with daily pill reminders, preappointment reminders, symptom reporting and management, and weekly health promotion tips. Mobile health tools are being increasingly used in resource-limited settings but are often adopted without rigorous evaluation.ObjectiveThis qualitative study conducted at 12 months after enrollment assessed patients' experiences, perceptions, and attitudes regarding CLFU.MethodsWe conducted a qualitative substudy within an open-label randomized controlled trial titled "Improving outcomes in HIV patients using mobile phone based interactive software support." Data were collected through 6 focus group discussions with participants sampled based on proportion of calls responded to-<25%, between 25% and 50%, and >50%-conducted at the Infectious Diseases Institute, Mulago, and the Kasangati Health Centre IV. NVivo (version 11; QSR International) was used in the management of the data and in the coding of the emerging themes. The data were then analyzed using content thematic analysis.ResultsThere was consensus across all groups that they had more positive than negative experiences with the CFLU system. Participants who responded to >50% of the calls reported more frequent use of the specific elements of the CFLU tool and, consequently, experienced more benefits from the system than those who responded to calls less frequently. Irrespective of calls responded to, participants identified pill reminders as the most important aspect in improved quality of life, followed by health promotion tips. The most common challenge faced was difficulty with the secret personal identification number.ConclusionsFindings showed participants' appreciation, high willingness, and interest in the intervention, CFLU, that demonstrated great perceived potential to improve their access to health care; adherence to treatment; health awareness; and, consequently, quality of life.Trial registrationClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080

Perceptions and Attitudes Toward an Interactive Voice Response Tool (Call for Life Uganda) Providing Adherence Support and Health Information to HIV-Positive Ugandans: Qualitative Study

BackgroundThe continuing decline in AIDS-related deaths in the African region is largely driven by the steady scale-up of antiretroviral therapy. However, there are challenges to retaining people living with HIV on treatment. Call for Life Uganda (CFLU) is an interactive voice response tool using simple analogue phones. CFLU supports patients with daily pill reminders, preappointment reminders, symptom reporting and management, and weekly health promotion tips. Mobile health tools are being increasingly used in resource-limited settings but are often adopted without rigorous evaluation. ObjectiveThis qualitative study conducted at 12 months after enrollment assessed patients’ experiences, perceptions, and attitudes regarding CLFU. MethodsWe conducted a qualitative substudy within an open-label randomized controlled trial titled “Improving outcomes in HIV patients using mobile phone based interactive software support.” Data were collected through 6 focus group discussions with participants sampled based on proportion of calls responded to—50%—conducted at the Infectious Diseases Institute, Mulago, and the Kasangati Health Centre IV. NVivo (version 11; QSR International) was used in the management of the data and in the coding of the emerging themes. The data were then analyzed using content thematic analysis. ResultsThere was consensus across all groups that they had more positive than negative experiences with the CFLU system. Participants who responded to >50% of the calls reported more frequent use of the specific elements of the CFLU tool and, consequently, experienced more benefits from the system than those who responded to calls less frequently. Irrespective of calls responded to, participants identified pill reminders as the most important aspect in improved quality of life, followed by health promotion tips. The most common challenge faced was difficulty with the secret personal identification number. ConclusionsFindings showed participants’ appreciation, high willingness, and interest in the intervention, CFLU, that demonstrated great perceived potential to improve their access to health care; adherence to treatment; health awareness; and, consequently, quality of life. Trial RegistrationClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT0295308

Perceptions and Attitudes Toward an Interactive Voice Response Tool (Call for Life Uganda) Providing Adherence Support and Health Information to HIV-Positive Ugandans: Qualitative Study.

BACKGROUND: The continuing decline in AIDS-related deaths in the African region is largely driven by the steady scale-up of antiretroviral therapy. However, there are challenges to retaining people living with HIV on treatment. Call for Life Uganda (CFLU) is an interactive voice response tool using simple analogue phones. CFLU supports patients with daily pill reminders, preappointment reminders, symptom reporting and management, and weekly health promotion tips. Mobile health tools are being increasingly used in resource-limited settings but are often adopted without rigorous evaluation. OBJECTIVE: This qualitative study conducted at 12 months after enrollment assessed patients' experiences, perceptions, and attitudes regarding CLFU. METHODS: We conducted a qualitative substudy within an open-label randomized controlled trial titled "Improving outcomes in HIV patients using mobile phone based interactive software support." Data were collected through 6 focus group discussions with participants sampled based on proportion of calls responded to-50%-conducted at the Infectious Diseases Institute, Mulago, and the Kasangati Health Centre IV. NVivo (version 11; QSR International) was used in the management of the data and in the coding of the emerging themes. The data were then analyzed using content thematic analysis. RESULTS: There was consensus across all groups that they had more positive than negative experiences with the CFLU system. Participants who responded to >50% of the calls reported more frequent use of the specific elements of the CFLU tool and, consequently, experienced more benefits from the system than those who responded to calls less frequently. Irrespective of calls responded to, participants identified pill reminders as the most important aspect in improved quality of life, followed by health promotion tips. The most common challenge faced was difficulty with the secret personal identification number. CONCLUSIONS: Findings showed participants' appreciation, high willingness, and interest in the intervention, CFLU, that demonstrated great perceived potential to improve their access to health care; adherence to treatment; health awareness; and, consequently, quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080

Prevalence and incidence of HIV in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda.

BackgroundLocal HIV epidemiology data are critical in determining the suitability of a population for HIV vaccine efficacy trials. The objective of this study was to estimate the prevalence and incidence of, and determine risk factors for HIV transmission in a rural community-based HIV vaccine preparedness cohort in Masaka, Uganda.MethodsBetween February and July 2004, we conducted a house-to-house HIV sero-prevalence survey among consenting individuals aged 18-60 years. Participants were interviewed, counseled and asked to provide blood for HIV testing. We then enrolled the HIV uninfected participants in a 2-year HIV sero-incidence study. Medical evaluations, HIV counseling and testing, and sample collection for laboratory analysis were done quarterly. Sexual risk behaviour data was collected every 6 months.ResultsThe HIV point prevalence was 11.2%, and was higher among women than men (12.9% vs. 8.6%, P = 0.007). Risk factors associated with prevalent HIV infection for men were age ConclusionsWe found a high prevalence but low incidence of HIV in this cohort. HIV vaccine efficacy trials in this population may not be feasible due to the large sample sizes that would be required. HIV vaccine preparatory efforts in this setting should include identification of higher risk populations