Marta Ackers

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.

Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

Objectives:To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. Design:Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). Methods:Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. Results:Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. Conclusions:Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States.

Objective:To evaluate for changes in sexual behaviors associated with daily pill use among men who have sex with men (MSM) participating in a preexposure prophylaxis trial. Design:Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to receive tenofovir disoproxil fumarate or placebo at enrollment or after a 9-month delay and followed for 24 months. Methods:Four hundred HIV-negative MSM reporting anal sex with a man in the past 12 months and meeting other eligibility criteria enrolled in San Francisco, Atlanta, and Boston. Sexual risk was assessed at baseline and quarterly visits using Audio Computer-Assisted Self-Interview. The association of pill taking with sexual behavior was evaluated using logistic and negative-binomial regressions for repeated measures. Results:Overall indices of behavioral risk declined or remained stable during follow-up. Mean number of partners and proportion reporting unprotected anal sex declined during follow-up (P < 0.05), and mean unprotected anal sex episodes remained stable. During the initial 9 months, changes in risk practices were similar in the group that began pills immediately vs. those in the delayed arm. These indices of risk did not differ significantly after initiation of pill use in the delayed arm or continuation of study medication in the immediate arm. Use of poppers, amphetamines, and sexual performance–enhancing drugs were independently associated with one or more indices of sexual risk. Conclusions:There was no evidence of risk compensation among HIV-uninfected MSM in this clinical trial. Monitoring for risk compensation should continue now that preexposure prophylaxis has been shown to be efficacious in MSM and other populations and will be provided in open-label trials and other contexts.

Screening for chronic hepatitis B and C virus infections in an urban sexually transmitted disease clinic: rationale for integrating services.

Background and Objectives Clients attending sexually transmitted disease (STD) clinics are at risk for multiple infections (e.g., STDs, HIV, and infectious viral hepatitis). Risk assessment and serosurveys can document the need for hepatitis screening and vaccination services. Goal To determine hepatitis C and B virus seroprevalence, identify predictive risk factors, and provide a rationale for integrating hepatitis services in an STD clinic. Methods During various periods in 1998, consecutive clients completed a self-administered risk assessment and were offered screening for markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (HBV core antibody and anti-HCV [enzyme-linked immunosorbent assay 3.0, confirmed by recombinant immunoblot assay 2.0]). Results Sixteen percent of 300 clients tested for an anti-HBV core were positive, with injecting-drug users (IDUs) and men who have sex with men (MSM) having higher prevalences (50% and 37%, respectively). Of 615 clients tested for anti-HCV, 21 (3.4%) were positive. Injecting-drug users (n = 34) had a 38% anti-HCV prevalence compared with 1.1% for non-IDUs. Of 66 non-IDU MSM tested, none was HCV infected. IDUs had a high prevalence of past STDs (> 50%) and unsafe sexual behavior. Conclusions Injecting drug users and MSM are at high risk for STDs, HIV, and hepatitis infections and could benefit from a “one-stop” STD clinic that included hepatitis prevention services.

HIV-1 Virologic and Immunologic Progression and Initiation of Antiretroviral Therapy among HIV-1–Infected Subjects in a Trial of the Efficacy of Recombinant Glycoprotein 120 Vaccine

The first trial of the efficacy of a human immunodeficiency virus (HIV)-1 vaccine was conducted in North America and The Netherlands between 1998 and 2003. This multicenter, randomized, placebo-controlled trial of a recombinant glycoprotein 120 vaccine included 5403 initially HIV-negative volunteers who were monitored for 3 years. The 368 subjects who acquired HIV-1 infection were monitored for 2 years by use of the following postinfection end points: plasma HIV-1 RNA level (viral load), CD4+ lymphocyte count, initiation of antiretroviral therapy (ART), and HIV-1-related clinical outcomes. This article reports the study results that pertain to the effect of vaccination on the postinfection end points. The time until initiation of ART and the time until virologic failure or initiation of ART were similar in the vaccine arm and the placebo arm. The pre-ART viral load and CD4+ lymphocyte count trajectories were also comparable between the groups. Evidently, the vaccine did not affect HIV-1 disease progression.

The adult population impact of HIV care and antiretroviral therapy in a resource poor setting 2003-2008.

Objective:To describe the population uptake of HIV care including antiretroviral therapy (ART) and its impact on adult mortality in a rural area of western Kenya with high HIV prevalence during a period of rapid HIV services scale-up. Design:Adult medical chart data were abstracted at health facilities providing HIV care/ART to residents of a Health and Demographic Surveillance System (HDSS) and linked with HDSS demographic and mortality data. Methods:We evaluated secular trends in patient characteristics across enrollment years and estimated proportions of HIV-positive adult residents receiving care. We evaluated adult (18–64 years) population mortality trends using verbal autopsy findings. Results:From 2003 to 2008, 5421 HDSS-resident adults enrolled in HIV care; 61.4% (n = 3331) were linked to HDSS follow-up data. As the number of facilities expanded from 1 (2003) to 17 (2008), receipt of HIV services by HIV-positive residents increased from less than 1 to 29.5%, and ART coverage reached 64.0% of adults with CD4 cell count less than 250 cells/&mgr;l. The proportion of patients with WHO stage 4 at enrollment decreased from 20.4 to 1.9%, and CD4 cell count testing at enrollment increased from 1.0 to 53.4%. Population-level mortality rates for adults declined 34% for all causes, 26% for AIDS/tuberculosis, and 47% for other infectious diseases; noninfectious disease mortality rates remained constant. Conclusion:The initial years of rapid HIV service expansion coincided with a drop in adult mortality by a third. Continued expansion of population access to HIV clinical services, including ART, and program quality improvements will be necessary to achieve further progress in reducing HIV-related morbidity and mortality.

Cholera and sliced fruit: Probable secondary transmission from an asymptomatic carrier in the United States

Abstract On September 8, 1995, two California residents developed diarrhea 15 hours after sharing a sliced cantaloupe. Stool culture from one person yielded toxigenic Vibrio cholerae O1, serotype Ogawa, biotype El Tor and the vibriocidal antibody titer was 10,240 for the second person, indicating recent infection with V. cholerae O1. A third person, who had sliced the cantaloupe, had recently returned from Guatemala but denied having gastrointestinal illness during or after the trip. Her vibriocidal antibody titer was 5120, also indicating recent infection with V. cholerae O1. This is the first reported incident of secondary transmission of cholera associated with an asymptomatic foodhandler. Encouraging good sanitary practices among foodhandlers and prompt refrigeration and consumption of sliced fruits may prevent further occurrences.

HIV Prevention in Care and Treatment Settings: Baseline Risk Behaviors among HIV Patients in Kenya, Namibia, and Tanzania

HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). Trial Registration ClinicalTrials.gov NCT01256463

Mortality Trends from 2003 to 2009 among Adolescents and Young Adults in Rural Western Kenya Using a Health and Demographic Surveillance System

Background Targeted global efforts to improve survival of young adults need information on mortality trends; contributions from health and demographic surveillance system (HDSS) are required. Methods and Findings This study aimed to explore changing trends in deaths among adolescents (15–19 years) and young adults (20–24 years), using census and verbal autopsy data in rural western Kenya using a HDSS. Mid-year population estimates were used to generate all-cause mortality rates per 100,000 population by age and gender, by communicable (CD) and non-communicable disease (NCD) causes. Linear trends from 2003 to 2009 were examined. In 2003, all-cause mortality rates of adolescents and young adults were 403 and 1,613 per 100,000 population, respectively, among females; and 217 and 716 per 100,000, respectively, among males. CD mortality rates among females and males 15–24 years were 500 and 191 per 100,000 (relative risk [RR] 2.6; 95% confidence intervals [CI] 1.7–4.0; p<0.001). NCD mortality rates in same aged females and males were similar (141 and 128 per 100,000, respectively; p = 0.76). By 2009, young adult female all-cause mortality rates fell 53% (χ2 for linear trend 30.4; p<0.001) and 61.5% among adolescent females (χ2 for linear trend 11.9; p<0.001). No significant CD mortality reductions occurred among males or for NCD mortality in either gender. By 2009, all-cause, CD, and NCD mortality rates were not significantly different between males and females, and among males, injuries equalled HIV as the top cause of death. Conclusions This study found significant reductions in adolescent and young adult female mortality rates, evidencing the effects of targeted public health programmes, however, all-cause and CD mortality rates among females remain alarmingly high. These data underscore the need to strengthen programmes and target strategies to reach both males and females, and to promote NCD as well as CD initiatives to reduce the mortality burden amongst both gender.

The study of HIV and antenatal care integration in pregnancy in Kenya: design, methods, and baseline results of a cluster-randomized controlled trial

Background Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma. Methodology/Principal Findings A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009– March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIV-free infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to socio-demographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines. Conclusions/Significance This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving to eliminate vertical transmission of HIV and improve maternal health. Trial Registration ClinicalTrials.gov NCT00931216 NCT00931216.