Richard Lester

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

BACKGROUND Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. METHODS WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. FINDINGS Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). INTERPRETATION Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. FUNDING US Presidents Emergency Plan for AIDS Relief.

Use of, effectiveness of, and attitudes regarding influenza vaccine among house staff.

OBJECTIVE To determine influenza vaccination rates, vaccine effectiveness, and factors influencing vaccination decisions among house staff. DESIGN Cross-sectional survey. SETTING AND PARTICIPANTS All residents registered at the University of Toronto were surveyed after the 1999-2000 influenza season. Of the 1,159 questionnaires mailed, 670 (58%) could be evaluated. RESULTS Influenza-like illnesses were reported by 36% of house staff. The vaccination rate was 51% among respondents, being highest for community and occupational medicine and pediatric staff (77% and 75%) and lowest for psychiatry, surgery, and radiology staff (32%, 36%, and 36%). Vaccinees reported significantly fewer episodes of illness (42 vs 54 per 100 subjects; P = .03) and fewer days of illness (272 vs 374 per 100 subjects; P = .02); absenteeism was not different (63 vs 69 per 100 subjects; P = .69). Self-protection was the most common reason for vaccination. Vaccinees believed the vaccine was more effective than did non-vaccinees (P < .01). Non-vaccinees considered influenza-like symptoms the most important side effect of the vaccine. Busy schedules and inconvenience were the most common reasons for not getting vaccinated. Overall, 44% of house staff believed the influenza vaccine should be mandatory. CONCLUSIONS Influenza-like illness was common among house staff. They tended to work through their illnesses, potentially putting patients at risk. They were motivated mostly by self-protection and did report a benefit. Despite busy schedules and an unfounded fear of getting influenza symptoms from the vaccine, many thought the vaccine should be mandatory.

HIV Status in Discordant Couples in Sub-Saharan Africa : A Systematic Review and Meta-Analysis

BACKGROUND Most couples affected by HIV/AIDS in sub-Saharan Africa live in discordant relationships. Men are thought to be the index case in most relationships, and most social marketing and awareness campaigns are focused on men. We investigated serodiscordance in stable relationships to establish the gender balance of index-case infections. METHODS We did a systematic review, random-effects meta-analysis, and meta-regression of published and unpublished studies enrolling discordant couples and assessed the proportion of men and women that were index cases. We repeated the analysis with data from demographic and health surveys (DHS) from the 14 countries that have documented the HIV status of couples. Our primary outcome was the total number of HIV discordant couples, including the proportion of HIV-positive women. FINDINGS We included data from 27 cohorts of 13,061 couples and DHS data from 14 countries of 1145 couples. The proportion of HIV-positive women in stable heterosexual serodiscordant relationships was 47% (95% CI 43-52), which shows that women are as likely as men to be the index partner in a discordant couple. DHS data (46%, 41-51) and our sensitivity analysis (47%, 43-52) showed similar findings. Meta-regression showed that urban versus rural residence (odds ratio 0.31, 95% CI 0.22-0.39), latitude (β coefficient 0.02, 0.023-0.034), gender equality (β coefficient -0.42, -0.56 to -0.27), HIV prevalence (β coefficient -0.037, -0.04 to -0.030), and older age (β coefficient 0.20, 0.08-0.32) were associated with the proportion of female index cases. INTERPRETATION Our study shows the need to focus on both sexes in HIV prevention strategies, such as promotion of condom use and mitigation of risk behaviours. FUNDING None.

The Cameroon Mobile Phone SMS (CAMPS) Trial: A Randomized Trial of Text Messaging versus Usual Care for Adherence to Antiretroviral Therapy

Background Mobile phone technology is a novel way of delivering health care and improving health outcomes. This trial investigates the use of motivational mobile phone text messages (SMS) to improve adherence to antiretroviral therapy (ART) over six months. Methodology/Principal Findings CAMPS was a single-site randomized two-arm parallel design trial in Yaoundé, Cameroon. We enrolled and randomized HIV-positive adults on ART, aged 21 years and above to receive a weekly standardized motivational text message versus usual care alone. The primary outcome was adherence measured using a visual analogue scale (VAS), number of doses missed (in the week preceding the interview) and pharmacy refill data. Outcomes were measured at 3 and 6 months. Service providers and outcome assessors were blinded to allocation. Analysis was by intention-to-treat. Between November and December 2010, 200 participants were randomized, with 101 in the intervention group and 99 in the control group. At 6 months, overall retention was 81.5%. We found no significant effect on adherence by VAS>95% (risk ratio [RR] 1.06, 95% confidence interval [CI] 0.89, 1.29; p = 0.542; reported missed doses (RR 1.01, 95% CI 0.87, 1.16; p>0.999) or number of pharmacy refills (mean difference [MD] 0.1, 95% CI: 0.23, 0.43; p = 0.617. One participant in the intervention arm reported a possible disclosure of status. Conclusions/Significance Standardized motivational mobile phone text messages did not significantly improve adherence to ART in this study. Other types of messaging or longer term studies are recommended. Registration 1. Pan-African Clinical Trials Registry; PACTR201011000261458 2. Clinicaltrials.gov; NCT01247181

Toll-like receptor expression and responsiveness are increased in viraemic HIV-1 infection

Objectives:Toll-like receptors (TLR) are important in pathogen recognition and may play a role in HIV disease. We evaluated the effect of chronic untreated and treated HIV-1 infection on systemic TLR expression and TLR signalling. Methods:Two hundred HIV-infected and uninfected women from a Kenya cohort participated in the studies. TLR1 to TLR10 messenger RNA expression was determined by quantitative reverse transcriptase polymerase chain reaction in peripheral blood mononuclear cells (PBMC). TLR ligand responsiveness was determined in or using ex-vivo PBMC by cytokine production in culture supernatants. Results:Chronic, untreated HIV-1 infection was significantly associated with increased mRNA expression of TLR6, TLR7, and TLR8 and when analysis was limited to those with advanced disease (CD4 cell count < 200 cells/ml) TLR2, TLR3, and TLR4 were additionally elevated. TLR expression correlated with the plasma HIV-RNA load, which was significant for TLR6 and TLR7. In vitro HIV single-stranded RNA alone could enhance TLR mRNA expression. PBMC of HIV-infected subjects also demonstrated profoundly increased proinflammatory responsiveness to TLR ligands, suggesting sensitization of TLR signalling in HIV. Finally, viral suppression by HAART was associated with a normalization of TLR levels. Conclusion:Together, these data indicate that chronic viraemic HIV-1 is associated with increased TLR expression and responsiveness, which may perpetuate innate immune dysfunction and activation that underlies HIV pathogenesis, and thus reveal potential new targets for therapy.

Mobile phone text messages for improving adherence to antiretroviral therapy (ART): a protocol for an individual patient data meta-analysis of randomised trials

Objectives Our objectives were to analyse the effects of text messaging versus usual care in improving adherence to antiretroviral therapy (ART) in people living with HIV using individual patient data meta-analysis. Adjusted, sensitivity and subgroup analyses were conducted. Setting 3 randomised controlled trials conducted between 2010 and 2012 in rural and urban centres in Cameroon and Kenya (two studies) were used. Participants A total of 1166 participants were included in this analysis (Cameroon=200; Kenya=428 and 538). Primary and secondary outcomes The primary outcome was adherence to ART >95%. The secondary outcomes were mortality, losses to follow-up, transfers and withdrawals. Results Text messaging improved adherence to ART (OR 1.38; 95% CIs 1.08 to 1.78; p=0.012), even after adjustment for baseline covariates (OR 1.46; 95% CI 1.13 to 1.88; p=0.004). Primary education (compared with no formal education) was associated with a greater intervention effect on adherence (OR 1.65; 95% CI 1.10 to 2.48; p=0.016) and also showed a significant subgroup effect (p=0.039). In sensitivity analysis, our findings were robust to a modified threshold of adherence, multiple imputation for missing data and aggregate level data pooling, but not to fixed-effects meta-analyses using generalised estimation equations. There was a significant subgroup effect for long weekly (p=0.037), short weekly text messages (p=0.014) and interactive messaging (p=0.010). Text messaging did not significantly affect any of the secondary outcomes. Conclusions Text messaging has a significant effect on adherence to ART, and this effect is influenced by level of education, gender, timing (weekly vs daily) and interactivity. We recommend the use of interactive weekly text messaging to improve adherence to ART, which is most effective in those with at least a primary level of education.

Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: A systematic review and meta-analysis

Background:HIV/AIDS has historically had a sex and gender-focused approach to prevention and care. Some evidence suggests that HIV-positive men have worse treatment outcomes than their women counterparts in Africa. Methods:We conducted a systematic review and meta-analysis of the effect of sex on the risk of death among participants enrolled in antiretroviral therapy (ART) programs in Africa since the rapid scale-up of ART. We included all cohort studies evaluating the effect of sex (male, female) on the risk of death among participants enrolled in regional and national ART programs in Africa. We identified these studies by searching MedLine, EMBASE, and Cochrane CENTRAL. We used a DerSimonian-Laird random-effects method to pool the proportions of men receiving ART and the hazard ratios for death by sex. Results:Twenty-three cohort studies, including 216 008 participants (79 892 men) contributed to our analysis. The pooled proportion of men receiving ART was 35% [95% confidence interval (CI): 33–38%]. The pooled hazard ratio estimate indicated a significant increase in the risk of death for men when compared to women [hazard ratio: 1.37 (95% CI: 1.28–1.47)]. This was consistent across sensitivity analyses. Interpretation:The proportion of men enrolled in ART programs in Africa is lower than women. Additionally, there is an increased risk of death for men enrolled in ART programs. Solutions that aid in reducing these sex inequities are needed.

M-health for health behaviour change in resource-limited settings: applications to HIV care and beyond

Of the new advanced information and communication technologies, cellular telecommunication networks and mobile phones have reached far more people than any other, especially in de -veloping countries. Although internet use has also increased substantially in recent years, in 2011 26% of the people in developing countries had internet access, whereas 79% had mobile or cellular phone subscriptions.

How complexity science can inform scale-up and spread in health care: understanding the role of self-organization in variation across local contexts.

Health care systems struggle to scale-up and spread effective practices across diverse settings. Failures in scale-up and spread (SUS) are often attributed to a lack of consideration for variation in local contexts among different health care delivery settings. We argue that SUS occurs within complex systems and that self-organization plays an important role in the success, or failure, of SUS. Self-organization is a process whereby local interactions give rise to patterns of organizing. These patterns may be stable or unstable, and they evolve over time. Self-organization is a major contributor to local variations across health care delivery settings. Thus, better understanding of self-organization in the context of SUS is needed. We re-examine two cases of successful SUS: 1) the application of a mobile phone short message service intervention to improve adherence to medications during HIV treatment scale up in resource-limited settings, and 2) MRSA prevention in hospital inpatient settings in the United States. Based on insights from these cases, we discuss the role of interdependencies and sensemaking in leveraging self-organization in SUS initiatives. We argue that self-organization, while not completely controllable, can be influenced, and that improving interdependencies and sensemaking among SUS stakeholders is a strategy for facilitating self-organization processes that increase the probability of spreading effective practices across diverse settings.

HIV-1 RNA Dysregulates the Natural TLR Response to Subclinical Endotoxemia in Kenyan Female Sex-Workers

Background Subclinical endotoxemia has been reported in HIV-1 infected persons and may drive systemic immune activation and pathogenesis. Proinflammatory responsiveness to endotoxin (LPS) is mediated by Toll-like receptor 4 (TLR4). We therefore examined the association between plasma LPS levels, HIV RNA, and TLR4 expression and cytokine responses in the blood of HIV infected and uninfected participants in a cohort of female sex-workers in Kenya. Methodology/Principal Findings Ex vivo plasma and peripheral blood mononuclear cells (PBMC) were assessed for LPS and TLR mRNA, respectively. The effects of HIV single stranded RNA, a TLR8 ligand, on TLR4 and LPS signaling were further assessed in short term PBMC culture. Both HIV uninfected and infected subjects frequently had low detectable LPS levels in their plasmas. Significantly increased LPS levels were associated with chronic HIV-1 infection, both treated and untreated, but not with other acute or semi-chronic conditions reported. In HIV-uninfected subjects, TLR4 mRNA expression levels correlated inversely with plasma LPS levels, suggesting chronic endotoxin ‘tolerance’ in vivo. A similar effect of reduced TLR4 mRNA was seen in short term PBMC culture after stimulation with LPS. Interestingly, the apparent in vivo tolerance effect was diminished in subjects with HIV infection. Additionally, pre-stimulation of PBMC with LPS lead to proinflammatory (TNF-α) tolerance to subsequent LPS stimulation; however, pre-treatment of PBMC with HIV single-stranded RNA40, could enhance TLR4-mediated LPS responsiveness in vitro. Conclusions/Significance Thus, dysregulation of endotoxin tolerance by HIV-1 RNA may exacerbate HIV chronic immune activation and pathogenesis.