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

INTRODUCTION: 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.

Evaluation of trypan blue stain in the TC20 automated cell counter as a point-of-care for the enumeration of viable cryptococcal cells in cerebrospinal fluid.

Cerebrospinal fluid (CSF) culture can determine a quantitative viability of Cryptococcus yeasts; however, culture has a long turnaround-time. The TC20 automated cell counter (Bio-Rad) is a benchtop instrument used to count cells in 30 seconds. In vitro studies suggest trypan blue staining can distinguish between viable and dead cryptococcal yeasts. We hypothesized that trypan blue staining with automated cell counting may provide rapid quantification of viable CSF Cryptococcus yeasts. In sum, 96 HIV-infected participants with cryptococcal meningitis were enrolled and provided 194 CSF specimens in Kampala, Uganda. Cryptococcosis was diagnosed by CSF cryptococcal antigen (CRAG). CSF was stained with trypan blue and quantified yeasts with the TC20 cell counter. We compared the log10 transformed cell counter readings with gating of 4-10 µm versus log10 quantitative Cryptococcus cultures/ml. TC20 showed more positive results (95.4%) overall than culture (78.4%) with reference to CSF CRAG. TC20 had higher readings compared to culture in most cases with only a 25% level of agreement between the two methods. TC20 had a poor correlation to culture throughout the 14 days of antifungal therapy. The median of log10 transformed counts were 5.22 (IQR = 4.79-5.44) for the TC20 and 3.99 (IQR = 2.59-5.14) for culture. Overall, a linear regression showed no significant relationship between the TC20 and culture (r = -0.0025; P = .92). TC20 automated cell counting with trypan blue staining was poorly predictive of the quantitative CSF culture and could not be used as a substitute for quantitative culture.

Effect of HIV Self-Testing on PrEP Adherence Among Gender-Diverse Sex Workers in Uganda: A Randomized Trial.

BACKGROUND: HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) are complementary tools that could empower sex workers to control their HIV protection, but few studies have jointly evaluated PrEP and HIVST in any setting. METHODS: The Empower Study was an open-label randomized trial in Uganda. Sex workers were offered F/tenofovir disoproxil fumarate and randomized 1:1 to monthly HIVST and quarterly in-clinic testing (intervention) or quarterly in-clinic HIV testing alone (standard of care) and followed up for 12 months. PrEP adherence was measured using electronic adherence monitoring and tenofovir diphosphate (TFV-DP) levels in dried blood spots. Adherence outcomes and sexual behaviors were compared by arm using generalized estimating equation models. RESULTS: We enrolled 110 sex workers: 84 cisgender women, 14 transgender women, 10 men who have sex with men, and 2 transgender men. The median age was 23 years. The 12-month retention was 75%. Nearly all (99.4%) used ≥1 HIVST kit. The proportion with TFV-DP levels ≥700 fmol/punch in the HIVST and standard of care arms at the 3-, 6-, 9-, and 12-month visits was 2.4%, 2.3%, 0%, and 0% and 7.9%, 0%, 0%, and 0%, respectively, with no differences by randomization arm (P > 0.2). Self-reported condomless sex acts with paying partners was similar by arm [adjusted incidence rate ratio 0.70; 95% confidence interval (CI): 0.42 to 1.17; P = 0.18]. One seroconversion occurred (HIV incidence, 0.9/100 person-years); TFV-DP was not detected at any visit. CONCLUSIONS: A gender-diverse sample of sex workers in Uganda used HIVST but not daily oral PrEP for HIV protection. Alternate approaches to promote PrEP use, including long-acting formulations, should be considered in this population.

Prevalence and predictors of asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae in a Ugandan population most at risk of HIV transmission.

The aim of this study was to establish the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in key populations at increased risk of transmission of HIV. Additionally, we aimed to identify the associated risk factors for asymptomatic sexually transmitted infections (STIs) and evaluate the acceptability of self-collected samples. Asymptomatic people living with HIV (PLHIV) in the following categories were offered testing: discordant couples, young adults, pregnant patients and those attending the 'most-at-risk-population' clinic. Patients provided first-pass urine, self-collected vaginal swabs or both to test for NG and CT by polymerase chain reaction using BD ProbeTec™. Patients also completed an acceptability questionnaire, including the negative partner of an HIV-positive participant. Three hundred and sixty-three PLHIV had an STI screen. Asymptomatic STIs were only diagnosed in women (prevalence 5.7%), overall prevalence 3.9% (n = 14). Factors independently associated with an STI in women were being under 25 years (OR 9.63 95% CI 1.56-59.5) and having more than one sexual partner (OR 8.06 95% CI 1.07-60.6). Four hundred and seven completed the acceptability questionnaire. More than 95% of patients found self-sampling easy and comfortable and 83.8% would believe the results. Women significantly preferred the option of self-sampling, 56.9% versus 29.3% of men (p < 0.001). Acceptability of self-sampling was high. Young women with or at risk of HIV are an important target for STI testing regardless of symptoms. There is need for diagnostic tests that are inexpensive, rapid and accurate especially in resource-limited settings.

An Interactive Voice Response Software to Improve the Quality of Life of People Living With HIV in Uganda: Randomized Controlled Trial.

BACKGROUND: Following the successful scale-up of antiretroviral therapy (ART), the focus is now on ensuring good quality of life (QoL) and sustained viral suppression in people living with HIV. The access to mobile technology in the most burdened countries is increasing rapidly, and therefore, mobile health (mHealth) technologies could be leveraged to improve QoL in people living with HIV. However, data on the impact of mHealth tools on the QoL in people living with HIV are limited to the evaluation of SMS text messaging; these are infeasible in high-illiteracy settings. OBJECTIVE: The primary and secondary outcomes were to determine the impact of interactive voice response (IVR) technology on Medical Outcomes Study HIV QoL scores and viral suppression at 12 months, respectively. METHODS: Within the Call for Life study, ART-experienced and ART-naïve people living with HIV commencing ART were randomized (1:1 ratio) to the control (no IVR support) or intervention arm (daily adherence and pre-appointment reminders, health information tips, and option to report symptoms). The software evaluated was Call for Life Uganda, an IVR technology that is based on the Mobile Technology for Community Health open-source software. Eligibility criteria for participation included access to a phone, fluency in local languages, and provision of consent. The differences in differences (DIDs) were computed, adjusting for baseline HIV RNA and CD4. RESULTS: Overall, 600 participants (413 female, 68.8%) were enrolled and followed-up for 12 months. In the intervention arm of 300 participants, 298 (99.3%) opted for IVR and 2 (0.7%) chose SMS text messaging as the mode of receiving reminders and health tips. At 12 months, there was no overall difference in the QoL between the intervention and control arms (DID=0.0; P=.99) or HIV RNA (DID=0.01; P=.94). At 12 months, 124 of the 256 (48.4%) active participants had picked up at least 50% of the calls. In the active intervention participants, high users (received >75% of reminders) had overall higher QoL compared to low users (received <25% of reminders) (92.2 versus 87.8, P=.02). Similarly, high users also had higher QoL scores in the mental health domain (93.1 versus 86.8, P=.008) and better appointment keeping. Similarly, participants with moderate use (51%-75%) had better viral suppression at 12 months (80/94, 85% versus 11/19, 58%, P=.006). CONCLUSIONS: Overall, there was high uptake and acceptability of the IVR tool. While we found no overall difference in the QoL and viral suppression between study arms, people living with HIV with higher usage of the tool showed greater improvements in QoL, viral suppression, and appointment keeping. With the declining resources available to HIV programs and the increasing number of people living with HIV accessing ART, IVR technology could be used to support patient care. The tool may be helpful in situations where physical consultations are infeasible, including the current COVID epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT02953080; https://clinicaltrials.gov/ct2/show/NCT02953080.

Significant rates of risky sexual behaviours among HIV-infected patients failing first-line ART: A sub-study of the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial.

There are limited data on the prevalence of risky sexual behaviours in individuals failing first-line antiretroviral therapy (ART) and changes in sexual behaviour after switch to second-line ART. We undertook a sexual behaviour sub-study of Ugandan adults enrolled in the Europe-Africa Research Network for the Evaluation of Second-line Therapy trial. A standardized questionnaire was used to collect sexual behaviour data and, in particular, risky sexual behaviours (defined as additional sexual partners to main sexual partner, inconsistent use of condoms, non-disclosure to sexual partners, and exchange of money for sex). Of the 79 participants enrolled in the sub-study, 62% were female, median age (IQR) was 37 (32-42) years, median CD4 cell count (IQR) was 79 (50-153) cells/µl, and median HIV viral load log was 4.9 copies/ml (IQR: 4.5-5.3) at enrolment. The majority were in long-term stable relationships; 69.6% had a main sexual partner and 87.3% of these had been sexually active in the preceding six months. At enrolment, around 20% reported other sexual partners, but this was higher among men than women (36% versus 6.7 %, p < 0.001). In 50% there was inconsistent condom use with their main sexual partner and a similar proportion with other sexual partners, both at baseline and follow-up. Forty-three per cent of participants had not disclosed their HIV status to their main sexual partner (73% with other sexual partners) at enrolment, which was similar in men and women. Overall, there was no significant change in these sexual behaviours over the 96 weeks following switch to second-line ART, but rate of non-disclosure of HIV status declined significantly (43.6% versus 19.6%, p <0.05). Among persons failing first-line ART, risky sexual behaviours were prevalent, which has implications for potential onward transmission of drug-resistant virus. There is need to intensify sexual risk reduction counselling and promotion of partner testing and disclosure, especially at diagnosis of treatment failure and following switch to second- or third-line ART.