Kara Wools-Kaloustian

Task-shifting of antiretroviral delivery from health care workers to persons living with HIV/AIDS: clinical outcomes of a community-based program in Kenya.

Objectives:To assess whether community-based care delivered by people living with HIV/AIDS (PLWAs) could replace clinic-based HIV care. Design:Prospective cluster randomized controlled clinical trial. Setting:Villages surrounding 1 rural clinic in western Kenya. Subjects:HIV-infected adults clinically stable on antiretroviral therapy (ART). Intervention:The intervention group received monthly Personal Digital Assistant supported home assessments by PLWAs with clinic appointments every 3 months. The control group received standard of care monthly clinic visits. Main Outcomes Measured:Viral load, CD4 count, Karnofsky score, stability of ART regimen, opportunistic infections, pregnancies, and number of clinic visits. Results:After 1 year, there were no significant intervention-control differences with regard to detectable viral load, mean CD4 count, decline in Karnofsky score, change in ART regimen, new opportunistic infection, or pregnancy rate. Intervention patients made half as many clinic visits as did controls (P < 0.001). Conclusions:Community-based care by PLWAs resulted in similar clinical outcomes as usual care but with half the number of clinic visits. This pilot study suggests that task-shifting and mobile technologies can deliver safe and effective community-based care to PLWAs, expediting ART rollout and increasing access to treatment while expanding the capacity of health care institutions in resource-constrained environments.

Cohort Profile: The international epidemiological databases to evaluate AIDS (IeDEA) in sub-Saharan Africa

In response to the HIV/AIDS pandemic in sub-Saharan Africa the African networks of IeDEA (International epidemiologic databases to Evaluate AIDS) aim to inform the scale-up of ART in the region through clinical and epidemiologic research. Funded by the National Institutes of Allergy and Infectious Diseases (NIAID) the objectives across the four African IeDEA regions (West Africa Central Africa East Africa and Southern Africa) are similar and cover all populations including pregnant women infants children adolescents and adult patients. They can be summarized as follows: (1) To prove robust evaluation of the delivery of ART in children adolescents and adults in sub-Saharan Africa with a focus on long-term program effectiveness and outcomes; (2) to describe the long-term temporal trends in regimen durability and tolerability and to examine monitoring strategies; (3) to describe important comorbidities and co-infections of HIV infection including malaria tuberculosis and cancer; (4) to examine the pregnancy- and HIV-related outcomes of women initiating ART during pregnancy and of infants exposed to HIV or ART in utero; (5) to develop and apply novel statistical methods to deal with missing data loss to follow-up competing risks and time-dependent confounding; (6) to establish procedures to link the HIV cohort data with other databases at local or national level. The present report provides an indicative summary of some of the major research themes and key findings as well as a discussion of the program’s strengths and weaknesses.

Clinical Practice Guideline for the Management of Chronic Kidney Disease in Patients Infected With HIV: 2014 Update by the HIV Medicine Association of the Infectious Diseases Society of America

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patients individual circumstances.

Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P=0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National Institute of Allergy and Infectious Diseases and the National Research Center; ClinicalTrials.gov number, NCT00089505.).

An electronic medical record system for ambulatory care of HIV-infected patients in Kenya

Administering and monitoring therapy is crucial to the battle against HIV/AIDS in sub-Saharan Africa. Electronic medical records (EMRs) can aid in documenting care, monitoring drug adherence and response to therapy, and providing data for quality improvement and research. Faculty at Moi University in Kenya and Indiana and University in the USA opened adult and pediatric HIV clinics in a national referral hospital, a district hospital, and six rural health centers in western Kenya using a newly developed EMR to support comprehensive outpatient HIV/AIDS care. Demographic, clinical, and HIV risk data, diagnostic test results, and treatment information are recorded on paper encounter forms and hand-entered into a central database that prints summary flowsheets and reminders for appropriate testing and treatment. There are separate modules for monitoring the Antenatal Clinic and Pharmacy. The EMR was designed with input from clinicians who understand the local community and constraints of providing care in resource poor settings. To date, the EMR contains more than 30,000 visit records for more than 4000 patients, almost half taking antiretroviral drugs. We describe the development and structure of this EMR and plans for future development that include wireless connections, tablet computers, and migration to a Web-based platform.

Outcomes of HIV-infected orphaned and non-orphaned children on antiretroviral therapy in western Kenya

Objectives:Determine outcome differences between orphaned and non-orphaned children receiving antiretroviral therapy (ART). Design:Retrospective review of prospectively recorded electronic data. Setting:Nine HIV clinics in western Kenya. Population:279 children on ART enrolled between August 2002 and February 2005. Main Measures:Orphan status, CD4%, sex- and age-adjusted height (HAZ) and weight (WAZ) z scores, ART adherence, mortality. Results:Median follow-up was 34 months. Cohort included 51% males and 54% orphans. At ART initiation (baseline), 71% of children had CDC clinical stage B or C disease. Median CD4% was 9% and increased dramatically the first 30 weeks of therapy, then leveled off. Parents and guardians reported perfect adherence at every visit for 75% of children. Adherence and orphan status were not significantly associated with CD4% response. Adjusted for baseline age, follow-up was significantly shorter among orphaned children (median 33 vs. 41 weeks, P = 0.096). One-year mortality was 7.1% for orphaned and 6.6% for non-orphaned children (P = 0.836). HAZ and WAZ were significantly below norm in both groups. With ART, HAZ remained stable, while WAZ tended to increase toward the norm, especially among non-orphans. Orphans showed identical weight gains as non-orphans the first 70 weeks after start of ART but experienced reductions afterwards. Conclusions:Good ART adherence is possible in western rural Kenya. ART for HIV-infected children produced substantial and sustainable CD4% improvement. Orphan status was not associated with worse short-term outcomes but may be a factor for long-term therapy response. ART alone may not be sufficient to reverse significant developmental lags in the HIV-positive pediatric population.

Sampling-based approaches to improve estimation of mortality among patient dropouts: Experience from a large PEPFAR-funded program in Western Kenya

Background Monitoring and evaluation (M&E) of HIV care and treatment programs is impacted by losses to follow-up (LTFU) in the patient population. The severity of this effect is undeniable but its extent unknown. Tracing all lost patients addresses this but census methods are not feasible in programs involving rapid scale-up of HIV treatment in the developing world. Sampling-based approaches and statistical adjustment are the only scaleable methods permitting accurate estimation of M&E indices. Methodology/Principal Findings In a large antiretroviral therapy (ART) program in western Kenya, we assessed the impact of LTFU on estimating patient mortality among 8,977 adult clients of whom, 3,624 were LTFU. Overall, dropouts were more likely male (36.8% versus 33.7%; p = 0.003), and younger than non-dropouts (35.3 versus 35.7 years old; p = 0.020), with lower median CD4 count at enrollment (160 versus 189 cells/ml; p<0.001) and WHO stage 3–4 disease (47.5% versus 41.1%; p<0.001). Urban clinic clients were 75.0% of non-dropouts but 70.3% of dropouts (p<0.001). Of the 3,624 dropouts, 1,143 were sought and 621 had their vital status ascertained. Statistical techniques were used to adjust mortality estimates based on information obtained from located LTFU patients. Observed mortality estimates one year after enrollment were 1.7% (95% CI 1.3%–2.0%), revised to 2.8% (2.3%–3.1%) when deaths discovered through outreach were added and adjusted to 9.2% (7.8%–10.6%) and 9.9% (8.4%–11.5%) through statistical modeling depending on the method used. The estimates 12 months after ART initiation were 1.7% (1.3%–2.2%), 3.4% (2.9%–4.0%), 10.5% (8.7%–12.3%) and 10.7% (8.9%–12.6%) respectively. Conclusions/Significance Abstract Assessment of the impact of LTFU is critical in program M&E as estimated mortality based on passive monitoring may underestimate true mortality by up to 80%. This bias can be ameliorated by tracing a sample of dropouts and statistically adjust the mortality estimates to properly evaluate and guide large HIV care and treatment programs.

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle- and high-income countries

Objective:To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. Methods:Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. Results:In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/&mgr;L between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/&mgr;L (76% increase), 88 to 135 cells/&mgr;L (53%), and 209 to 274 cells/&mgr;L (31%). In 2009, compared with LIC, median counts were 13 cells/&mgr;L [95% confidence interval (CI): −56 to +30] lower in LMIC, 22 cells/&mgr;L (−62 to +18) lower in UMIC, and 112 cells/&mgr;L (+75 to +149) higher in HIC. They were 23 cells/&mgr;L (95% CI: +18 to +28 cells/&mgr;L) higher in women than men. Median counts were 88 cells/&mgr;L (95% CI: +35 to +141 cells/&mgr;L) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. Conclusions:Median CD4 cell counts at the start of cART increased 2000–2009 but remained below 200 cells/&mgr;L in LIC and MIC and below 300 cells/&mgr;L in HIC. Earlier start of cART will require substantial efforts and resources globally.

‘Wamepotea’ (They have become lost): Outcomes of HIV-positive and HIV-exposed children lost to follow-up from a large HIV treatment program in western Kenya

Objective:The objective of this study was to identify the vital status and reasons for children becoming loss to follow-up (LTFU) from a large program in western Kenya. Methods:This was a prospective evaluation of a random sample of 30% of HIV-exposed and HIV-positive children LTFU from either an urban or rural HIV Academic Model Providing Access to Healthcare clinic. LTFU is defined as absence from clinic for >6 months if on combination antiretroviral therapy and > 12 months if not. Experienced community health workers were engaged to locate them. Results:There were 97 children sampled (78 urban, 19 rural). Of these, 82% were located (78% urban, 100% rural). Among the HIV positive, 16% of the children were deceased, and 16% had not returned to clinic because of disclosure issues/discrimination in the family or community. Among the HIV exposed, 30% never returned to care because their guardians either had not disclosed their own HIV status or were afraid of family/community stigma related to their HIV status or that of the child. Among children whose HIV status was unknown, 29% of those found had actually died, and disclosure/discrimination accounted for 14% of the reasons for becoming LTFU. Other reasons included believing the child was healed by faith or through the use of traditional medicine (7%), transport costs (6%), and transferring care to other programs or clinics (8%). Conclusion:After locating >80% of the children in our sample, we identified that mortality and disclosure issues including fear of family or community discrimination were the most important reasons why these children became LTFU.

Outcomes of HIV-exposed children in western Kenya: efficacy of prevention of mother to child transmission in a resource-constrained setting.

Objectives:To compare rates of mother to child transmission of HIV and infant survival in women-infant dyads receiving different interventions in a prevention of Mother to Child Transmission (pMTCT) program in western Kenya. Design:Retrospective cohort study using prospectively collected data stored in an electronic medical record system. Setting:Eighteen HIV clinics in western Kenya. Population:HIV-exposed infants enrolled between February 2002 and July 2007, at any of the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership clinics. Main outcome measures:Combined endpoint (CE) of infant HIV status and mortality at 3 and 18 months. Analysis:Descriptive statistics, χ2 Fisher exact test, and multivariable modeling. Results:Between February 2002 and July 2007, 2477 HIV-exposed children were registered for care by the United States Agency for International Development-Academic Model Providing Access To Healthcare partnership pMTCT program before 3 months of age. Median age at enrollment was 6.1 weeks; 50.4% infants were male. By 3 months, 31 of 2477 infants (1.3%) were dead and 183 (7.4%) were lost to follow-up. One thousand (40%) underwent HIV DNA Polymerase Chain Reaction virologic test at a median age of 8.3 weeks: 5% were HIV infected, 89% uninfected, and 6% were indeterminate. Of the 968 infants with specific test results or mortality data at 3 months, the CE of HIV infection or death was reached in 84 of 968 (8.7%) infants. The 3-month CE was significantly impacted (A) by maternal prophylaxis [51 of 752 (6.8%) combination antiretroviral therapy (cART); 8 of 69 (11.6%) single-dose nevirapine (sdNVP); and 25 of 147 (17%) no prophylaxis (P < 0.001)] and (B) by feeding method for the 889 of 968 (91.8%) mother-infant pairs for which feeding choice was documented [5 of 29 (17.2%) exclusive breastfeeding; 13 of 110 (11.8%) mixed feeding; and 54 of 750 (7.2%) formula feeding (P = 0.041)]. Of the 1201 infants ≥18 months of age: 41 (3.4%) were deceased and 329 (27.4%) were lost to follow-up. Of 621 of 831 (74.7%) infants tested, 65 (10.5%) were infected resulting in a CE of 103 of 659 (15.6%). CE differed significantly by maternal prophylaxis [52 of 441 (11.8%) for cART; 13 of 96 (13.5%) for sdNVP; and 38 of 122 (31.2%) no therapy group (P < 0.001)] but not by feeding method for the 638 of 659 (96.8%) children with documented feeding choice [7 of 35 (20%) exclusive breastfeeding, 14 of 63 (22.2%) mixed, and 74 of 540 (13.7%) formula (P = 0.131)]. On multivariate analysis, sdNVP (odds ratio: 0.4; 95% confidence interval: 0.2 to 0.8) and cART (odds ratio: 0.3; 95% confidence interval: 0.2 to 0.6) were associated with fewer CE. At 18 months, feeding method was not significantly associated with the CE. Conclusions:Though ascertainment bias is likely, results strongly suggest a benefit of antiretroviral prophylaxis in reducing infant death and HIV infection, but do not show a benefit at 18-months from the use of formula. There was a high rate of loss to follow up, and adherence to the HIV infant testing protocol was less than 50% indicating the need to address barriers related to infant HIV testing, and to improve outreach and follow-up services.