Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya.

Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2-35.7), 33.1% (95% CI 24.7-42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1-35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing.

Implementation and Operational Research: Effects of Antenatal Care and HIV Treatment Integration on Elements of the PMTCT Cascade: Results From the SHAIP Cluster-Randomized Controlled Trial in Kenya.

BACKGROUND: Integrating antenatal care (ANC) and HIV care may improve uptake and retention in services along the prevention of mother-to-child transmission (PMTCT) cascade. This study aimed to determine whether integration of HIV services into ANC settings improves PMTCT service utilization outcomes. METHODS: ANC clinics in rural Kenya were randomized to integrated (6 clinics, 569 women) or nonintegrated (6 clinics, 603 women) services. Intervention clinics provided all HIV services, including highly active antiretroviral therapy (HAART), whereas control clinics provided PMTCT services but referred women to HIV care clinics within the same facility. PMTCT utilization outcomes among HIV-infected women (maternal HIV care enrollment, HAART initiation, and 3-month infant HIV testing uptake) were compared using generalized estimating equations and Cox regression. RESULTS: HIV care enrollment was higher in intervention compared with control clinics [69% versus 36%; odds ratio = 3.94, 95% confidence interval (CI): 1.14 to 13.63]. Median time to enrollment was significantly shorter among intervention arm women (0 versus 8 days, hazard ratio = 2.20, 95% CI: 1.62 to 3.01). Eligible women in the intervention arm were more likely to initiate HAART (40% versus 17%; odds ratio = 3.22, 95% CI: 1.81 to 5.72). Infant testing was more common in the intervention arm (25% versus 18%), however, not statistically different. No significant differences were detected in postnatal service uptake or maternal retention. CONCLUSIONS: Service integration increased maternal HIV care enrollment and HAART uptake. However, PMTCT utilization outcomes were still suboptimal, and postnatal service utilization remained poor in both study arms. Further improvements in the PMTCT cascade will require additional research and interventions.

Implementation and Operational Research: Effect of Integration of HIV Care and Treatment Into Antenatal Care Clinics on Mother-to-Child HIV Transmission and Maternal Outcomes in Nyanza, Kenya: Results From the SHAIP Cluster Randomized Controlled Trial.

BACKGROUND: Many HIV-infected pregnant women identified during antenatal care (ANC) do not enroll in long-term HIV care, resulting in deterioration of maternal health and continued risk of HIV transmission to infants. METHODS: We performed a cluster randomized trial to evaluate the effect of integrating HIV care into ANC clinics in rural Kenya. Twelve facilities were randomized to provide either integrated services (ANC, prevention of mother-to-child transmission, and HIV care delivered in the ANC clinic; n = 6 intervention facilities) or standard ANC services (including prevention of mother-to-child transmission and referral to a separate clinic for HIV care; n = 6 control facilities). RESULTS: There were high patient attrition rates over the course of this study. Among study participants who enrolled in HIV care, there was 12-month follow-up data for 256 of 611 (41.8%) women and postpartum data for only 325 of 1172 (28%) women. By 9 months of age, 382 of 568 (67.3%) infants at intervention sites and 338 of 594 (57.0%) at control sites had tested for HIV [odds ratio (OR) 1.45, 95% confidence interval (CI): 0.71 to 2.82]; 7.3% of infants tested HIV positive at intervention sites compared with 8.0% of infants at control sites (OR 0.89, 95% CI: 0.56 to 1.43). The composite clinical/immunologic progression into AIDS was similar in both arms (4.9% vs. 5.1%, OR 0.83, 95% CI: 0.41 to 1.68). CONCLUSIONS: Despite the provision of integrated services, patient attrition was substantial in both arms, suggesting barriers beyond lack of service integration. Integration of HIV services into the ANC clinic was not associated with a reduced risk of HIV transmission to infants and did not appear to affect short-term maternal health outcomes.

Pregnancy desire and dual method contraceptive use among people living with HIV attending clinical care in Kenya, Namibia and Tanzania.

AIM: To describe factors associated with pregnancy desire and dual method use among people living with HIV in clinical care in sub-Saharan Africa. DESIGN: Sexually active HIV-positive adults were enrolled in 18 HIV clinics in Kenya, Namibia and Tanzania. Demographic, clinical and reproductive health data were captured by interview and medical record abstraction. Correlates of desiring a pregnancy within the next 6 months, and dual method use [defined as consistent condom use together with a highly effective method of contraception (hormonal, intrauterine device (IUD), permanent)], among those not desiring pregnancy, were identified using logistic regression. RESULTS: Among 3375 participants (median age 37 years, 42% male, 64% on antiretroviral treatment), 565 (17%) desired a pregnancy within the next 6 months. Of those with no short-term fertility desire (n=2542), 686 (27%) reported dual method use, 250 (10%) highly effective contraceptive use only, 1332 (52%) condom use only, and 274 (11%) no protection. Respondents were more likely to desire a pregnancy if they were from Namibia and Tanzania, male, had a primary education, were married/cohabitating, and had fewer children. Factors associated with increased likelihood of dual method use included being female, being comfortable asking a partner to use a condom, and communication with a health care provider about family planning. Participants who perceived that their partner wanted a pregnancy were less likely to report dual method use. CONCLUSIONS: There was low dual method use and low use of highly effective contraception. Contraceptive protection was predominantly through condom-only use. These findings demonstrate the importance of integrating reproductive health services into routine HIV care.

The impact of home-based HIV counseling and testing on care-seeking and incidence of common infectious disease syndromes in rural western Kenya.

BACKGROUND: In much of Africa, most individuals living with HIV do not know their status. Home-based counseling and testing (HBCT) leads to more HIV-infected people learning their HIV status. However, there is little data on whether knowing one's HIV-positive status necessarily leads to uptake of HIV care, which could in turn, lead to a reduction in the prevalence of common infectious disease syndromes. METHODS: In 2008, Kenya Medical Research Institute (KEMRI) in collaboration with the Centers for Disease Control and Prevention (CDC) offered HBCT to individuals (aged ≥13 years) under active surveillance for infectious disease syndromes in Lwak in rural western Kenya. HIV test results were linked to morbidity and healthcare-seeking data collected by field workers through bi-weekly home visits. We analyzed changes in healthcare seeking behaviors using proportions, and incidence (expressed as episodes per person-year) of acute respiratory illness (ARI), severe acute respiratory illness (SARI), acute febrile illness (AFI) and diarrhea among first-time HIV testers in the year before and after HBCT, stratified by their test result and if HIV-positive, whether they sought care at HIV Patient Support Centers (PSCs). RESULTS: Of 9,613 individuals offered HBCT, 6,366 (66%) were first-time testers, 698 (11%) of whom were HIV-infected. One year after HBCT, 50% of HIV-infected persons had enrolled at PSCs - 92% of whom had started cotrimoxazole and 37% of those eligible for antiretroviral treatment had initiated therapy. Among HIV-infected persons enrolled in PSCs, AFI and diarrhea incidence decreased in the year after HBCT (rate ratio [RR] 0.84; 95% confidence interval [CI] 0.77 - 0.91 and RR 0.84, 95% CI 0.73 - 0.98, respectively). Among HIV-infected persons not attending PSCs and among HIV-uninfected persons, decreases in incidence were significantly lower. While decreases also occurred in rates of respiratory illnesses among HIV-positive persons in care, there were similar decreases in the other two groups. CONCLUSIONS: Large scale HBCT enabled a large number of newly diagnosed HIV-infected persons to know their HIV status, leading to a change in care seeking behavior and ultimately a decrease in incidence of common infectious disease syndromes through appropriate treatment and care.

Health care utilization and access to human immunodeficiency virus (HIV) testing and care and treatment services in a rural area with high HIV prevalence, Nyanza Province, Kenya, 2007.

We present health and demographic surveillance system data to assess associations with health care utilization and human immunodeficiency virus (HIV) service receipt in a high HIV prevalence area of western Kenya. Eighty-six percent of 15,302 residents indicated a facility/clinician for routine medical services; 60% reported active (within the past year) attendance. Only 34% reported a previous HIV test, and self-reported HIV prevalence was 6%. Active attendees lived only slightly closer to their reported service site (2.8 versus 3.1 km; P < 0.001) compared with inactive attendees. Multivariate analysis showed that younger respondents (< 30 years of age) and active and inactive attendees were more likely to report an HIV test compared with non-attendees; men were less likely to report HIV testing. Despite traveling farther for HIV services (median distance = 4.4 km), 77% of those disclosing HIV infection reported HIV care enrollment. Men and younger respondents were less likely to enroll in HIV care. Socioeconomic status was not associated with HIV service use. Distance did not appear to be the major barrier to service receipt. The health and demographic surveillance system data identified patterns of service use that are useful for future program planning.

HIV prevention in care and treatment settings: baseline risk behaviors among HIV patients in Kenya, Namibia, and Tanzania.

UNLABELLED: 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.

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.

Early uptake of HIV clinical care after testing HIV-positive during home-based testing and counseling in western Kenya.

Home-based HIV testing and counseling (HBTC) has the potential to increase access to HIV testing. However, the extent to which HBTC programs successfully link HIV-positive individuals into clinical care remains unclear. To determine factors associated with early enrollment in HIV clinical care, adult residents (aged ≥13 years) in the Health and Demographic Surveillance System in Kisumu, Kenya were offered HBTC. All HIV-positive residents were referred to nearby HIV clinical care centers. Two to four months after HBTC, peer educators conducted home visits to consenting HIV-positive residents. Overall, 9,895 (82 %) of 12,035 residents accepted HBTC; 1,087 (11 %) were HIV-positive; and 737 (68 %) received home visits. Of those receiving home visits, 42 % reported HIV care attendance. Factors associated with care attendance included: having disclosed, living with someone attending HIV care, and wanting to seek care after diagnosis. Residents who reported their current health as excellent or who doubted their HBTC result were less likely to report care attendance. While findings indicate that HBTC was well-received in this setting, less than half of HIV-positive individuals reported current care attendance. Identification of effective strategies to increase early enrollment and retention in HIV clinical care is critical and will require coordination between testing and treatment program staff and systems.

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% (χ(2) for linear trend 30.4; p<0.001) and 61.5% among adolescent females (χ(2) 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 http://clinicaltrials.gov/ct2/show/NCT00931216.

High and persistent HIV seroincidence in men who have sex with men across 47 U.S. cities.

OBJECTIVE: To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion. METHODS: From 1998-2002, 4684 high-risk MSM, age 18-60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional hazard model with time-varying covariates. RESULTS: Overall, HIV incidence was 2.7/100 py and was relatively uniform across study sites and study years. HIV incidence was highest among young men and men reporting unprotected sex, recreational drug use, and a history of a sexually transmitted infection. Independent predictors of HIV seroconversion included: age 18-30 years (aHR = 2.4; 95% CI 1.4,4.0), having >10 partners (aHR = 2.4; 95% CI 1.7,3.3), having a known HIV-positive male sex partner (aHR = 1.6; 95% CI 1.2, 2.0), unprotected anal intercourse with HIV positive/unknown male partners (aHR = 1.7; 95% CI 1.3, 2.3), and amphetamine (aHR = 1.6; 95% CI 1.1, 2.1) and popper (aHR = 1.7; 95% CI 1.3, 2.2) use. CONCLUSIONS: HIV seroincidence was high among MSM despite repeated HIV counseling and reported declines in sexual risk behaviors. Continuing development of new HIV prevention strategies and intensification of existing efforts will be necessary to reduce the rate of new HIV infections, especially among young men.

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/µl. 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.

Tuberculosis among children in Kenya: epidemiology and impact of HIV in two provinces.

We collected clinical register data on children in two provinces of Kenya and conducted bivariate and multivariate analyses to assess characteristics associated with death. Among 987 children with tuberculosis (TB), pulmonary disease was diagnosed in 689 (70%) children. Final outcomes were known for 830 children, 40 (5%) of whom died during TB treatment. HIV test results were available for 670 (68%) children; 371 (55%) of whom tested positive. Only 63 of 134 (47%) of children <1 year were tested for HIV. There were no data on CD4 or anti-retroviral use. The relative risk for death for HIV-infected children compared to HIV-uninfected children was 9.3 for children <1 year [95% confidence interval (CI) 1.2-69.2], 3.9 for children aged 1-4 (95% CI 0.9-17.7) and 0.9 for children aged 5-14 (95% CI 0.3-2.6). In Kenya, HIV infection in children with TB is common, and our data suggest that HIV is particularly deadly in TB patients <1 year, the group with the lowest rate of testing. Poor data recording and reporting limit our understanding of TB in this age group. Expansion of HIV testing may improve survival, and more complete data recording and reporting will enhance our understanding of pediatric TB.

Knowing a sexual partner is HIV-1-uninfected is associated with higher condom use among HIV-1-infected adults in Kenya.

The relation between awareness of sexual partner's HIV serostatus and unprotected sex was examined in HIV clinic enrollees. Increased condom use was associated with knowing that a partner was HIV-negative (adjusted odds ratio = 5.99; P < 0.001) versus not knowing partner's status. Partner testing may increase condom use in discordant couples.

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 President's Emergency Plan for AIDS Relief.

The HAART cell phone adherence trial (WelTel Kenya1): a randomized controlled trial protocol.

BACKGROUND: The objectives are to compare the effectiveness of cell phone-supported SMS messaging to standard care on adherence, quality of life, retention, and mortality in a population receiving antiretroviral therapy (ART) in Nairobi, Kenya. METHODS AND DESIGN: A multi-site randomized controlled open-label trial. A central randomization centre provided opaque envelopes to allocate treatments. Patients initiating ART at three comprehensive care clinics in Kenya will be randomized to receive either a structured weekly SMS ('short message system' or text message) slogan (the intervention) or current standard of care support mechanisms alone (the control). Our hypothesis is that using a structured mobile phone protocol to keep in touch with patients will improve adherence to ART and other patient outcomes. Participants are evaluated at baseline, and then at six and twelve months after initiating ART. The care providers keep a weekly study log of all phone based communications with study participants. Primary outcomes are self-reported adherence to ART and suppression of HIV viral load at twelve months scheduled follow-up. Secondary outcomes are improvements in health, quality of life, social and economic factors, and retention on ART. Primary analysis is by 'intention-to-treat'. Sensitivity analysis will be used to assess per-protocol effects. Analysis of covariates will be undertaken to determine factors that contribute or deter from expected and determined outcomes. DISCUSSION: This study protocol tests whether a novel structured mobile phone intervention can positively contribute to ART management in a resource-limited setting.

Modeling the impact of HIV chemoprophylaxis strategies among men who have sex with men in the United States: HIV infections prevented and cost-effectiveness.

BACKGROUND AND OBJECTIVE: HIV chemoprophylaxis may be a future prevention strategy to help control the global epidemic of HIV/AIDS. Safety and efficacy trials of two agents are currently underway. We assess the expected number of HIV cases prevented and cost-effectiveness of a hypothetical HIV chemoprophylaxis program among men who have sex with men in a large US city. DESIGN AND METHODS: We developed a stochastic compartmental mathematical model using HIV/AIDS surveillance data to simulate the HIV epidemic and the impact of a 5-year chemoprophylaxis program under varying assumptions for epidemiological, behavioral, programmatic and cost parameters. We estimated program effectiveness and costs from the perspective of the US healthcare system compared with current HIV prevention practices. The main outcome measures were number of HIV infections prevented and incremental cost per quality-adjusted life-years saved. RESULTS: A chemoprophylaxis program targeting 25% of high-risk men who have sex with men in New York City could prevent 780 (4%) to 4510 (23%) of the 19 510 HIV infections predicted to occur among all men who have sex with men in New York City in 5 years. More than half of prevented infections would be among those not taking chemoprophylaxis but who benefit from reduced HIV prevalence in the community. Under base-case assumptions, incremental cost was US$ 31 970 per quality-adjusted life-years saved. The program was cost-effective under most variations in efficacy, mechanism of protection and adherence. CONCLUSION: HIV chemoprophylaxis among high-risk men who have sex with men in a major US city could prevent a significant number of HIV infections and be cost-effective.

Mucosal HIV-binding antibody and neutralizing activity in high-risk HIV-uninfected female participants in a trial of HIV-vaccine efficacy.

BACKGROUND: This study investigated gp120-binding antibody and neutralizing activity, at the gingival- and cervical-mucosal levels, in response to a bivalent gp120 candidate vaccine. METHODS: Women who met the study's inclusion criteria for documented high-risk behaviors participated in a nested substudy of the multicenter phase 3 trial of human immunodeficiency virus (HIV)-vaccine efficacy, VAX004. Gingival, cervicovaginal lavage, and plasma specimens were collected at 6-month intervals for 3 years. Binding-antibody and neutralizing-activity assays quantified the presence of anti-HIV activity in mucosal specimens. RESULTS: Vaccine recipients were more likely than placebo recipients to have IgG binding antibodies in all 3 compartments tested and to have only IgA binding antibody in plasma (P<.0001). The relationship between vaccine and cervicovaginal IgG achieved significance (odds ratio [OR], 6.6 [P=.01]) but was weakened by the presence of cervicovaginal leukocytes. There was no relationship between immunization and the presence of neutralizing activity, in either bivariate or multivariate modeling (OR, 6.0 [P=.29]). CONCLUSIONS: Vaccination is associated with the presence of both gp120-binding IgG in all compartments and plasma IgA but not with neutralizing activity. There is a role for the measurement of mucosal immunity in response to candidate vaccines and, in particular, for a determination of HIV-specific neutralizing antibodies.