Publications
Trends in the clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009.
BACKGROUND: East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described. METHODS: We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors. RESULTS: Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis. CONCLUSIONS: Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed. AbstractBACKGROUND:East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described.METHODS:We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors.RESULTS:Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis.CONCLUSIONS:Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed.
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, chi 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 > or = 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. AbstractOBJECTIVES: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, chi 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 > or = 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.
Influence of gender on loss to follow-up in a large HIV treatment programme in western Kenya.
OBJECTIVE: To determine the incidence of loss to follow-up in a treatment programme for people living with human immunodeficiency virus (HIV) infection in Kenya and to investigate how loss to follow-up is affected by gender. METHODS: Between November 2001 and November 2007, 50 275 HIV-positive individuals aged ≥ 14 years (69% female; median age: 36.2 years) were enrolled in the study. An individual was lost to follow-up when absent from the HIV treatment clinic for > 3 months if on combination antiretroviral therapy (cART) or for > 6 months if not. The incidence of loss to follow-up was calculated using Kaplan-Meier methods and factors associated with loss to follow-up were identified by logistic and Cox multivariate regression analysis. FINDINGS: Overall, 8% of individuals attended no follow-up visits, and 54% of them were lost to follow-up. The overall incidence of loss to follow-up was 25.1 per 100 person-years. Among the 92% who attended at least one follow-up visit, the incidence of loss to follow-up before and after starting cART was 27.2 and 14.0 per 100 person-years, respectively. Baseline factors associated with loss to follow-up included younger age, a long travel time to the clinic, patient disclosure of positive HIV status, high CD4+ lymphocyte count, advanced-stage HIV disease, and rural clinic location. Men were at an increased risk overall and before and after starting cART. CONCLUSION: The risk of being lost to follow-up was high, particularly before starting cART. Men were more likely to become lost to follow-up, even after adjusting for baseline sociodemographic and clinical characteristics. Interventions designed for men and women separately could improve retention. AbstractOBJECTIVE:To determine the incidence of loss to follow-up in a treatment programme for people living with human immunodeficiency virus (HIV) infection in Kenya and to investigate how loss to follow-up is affected by gender.METHODS:Between November 2001 and November 2007, 50 275 HIV-positive individuals aged ≥ 14 years (69% female; median age: 36.2 years) were enrolled in the study. An individual was lost to follow-up when absent from the HIV treatment clinic for > 3 months if on combination antiretroviral therapy (cART) or for > 6 months if not. The incidence of loss to follow-up was calculated using Kaplan-Meier methods and factors associated with loss to follow-up were identified by logistic and Cox multivariate regression analysis.FINDINGS:Overall, 8% of individuals attended no follow-up visits, and 54% of them were lost to follow-up. The overall incidence of loss to follow-up was 25.1 per 100 person-years. Among the 92% who attended at least one follow-up visit, the incidence of loss to follow-up before and after starting cART was 27.2 and 14.0 per 100 person-years, respectively. Baseline factors associated with loss to follow-up included younger age, a long travel time to the clinic, patient disclosure of positive HIV status, high CD4+ lymphocyte count, advanced-stage HIV disease, and rural clinic location. Men were at an increased risk overall and before and after starting cART.CONCLUSION:The risk of being lost to follow-up was high, particularly before starting cART. Men were more likely to become lost to follow-up, even after adjusting for baseline sociodemographic and clinical characteristics. Interventions designed for men and women separately could improve retention.
Cross-Sectional Analysis of Late HAART Initiation in Latin America and the Caribbean: Late Testers and Late Presenters.
BACKGROUND: Starting HAART in a very advanced stage of disease is assumed to be the most prevalent form of initiation in HIV-infected subjects in developing countries. Data from Latin America and the Caribbean is still lacking. Our main objective was to determine the frequency, risk factors and trends in time for being late HAART initiator (LHI) in this region. METHODOLOGY: Cross-sectional analysis from 9817 HIV-infected treatment-naïve patients initiating HAART at 6 sites (Argentina, Chile, Haiti, Honduras, Peru and Mexico) from October 1999 to July 2010. LHI had CD4(+) count ≤200 cells/mm(3) prior to HAART. Late testers (LT) were those LHI who initiated HAART within 6 months of HIV diagnosis. Late presenters (LP) initiated after 6 months of diagnosis. Prevalence, risk factors and trends over time were analyzed. PRINCIPAL FINDINGS: Among subjects starting HAART (n = 9817) who had baseline CD4(+) available (n = 8515), 76% were LHI: Argentina (56%[95%CI:52-59]), Chile (80%[95%CI:77-82]), Haiti (76%[95%CI:74-77]), Honduras (91%[95%CI:87-94]), Mexico (79%[95%CI:75-83]), Peru (86%[95%CI:84-88]). The proportion of LHI statistically changed over time (except in Honduras) (p≤0.02; Honduras p = 0.7), with a tendency towards lower rates in recent years. Males had increased risk of LHI in Chile, Haiti, Peru, and in the combined site analyses (CSA). Older patients were more likely LHI in Argentina and Peru (OR 1.21 per +10-year of age, 95%CI:1.02-1.45; OR 1.20, 95%CI:1.02-1.43; respectively), but not in CSA (OR 1.07, 95%CI:0.94-1.21). Higher education was associated with decreased risk for LHI in Chile (OR 0.92 per +1-year of education, 95%CI:0.87-0.98) (similar trends in Mexico, Peru, and CSA). LHI with date of HIV-diagnosis available, 55% were LT and 45% LP. CONCLUSION: LHI was highly prevalent in CCASAnet sites, mostly due to LT; the main risk factors associated were being male and older age. Earlier HIV-diagnosis and earlier treatment initiation are needed to maximize benefits from HAART in the region.
Risk factors for tuberculosis after highly active antiretroviral therapy initiation in the United States and Canada: implications for tuberculosis screening.
BACKGROUND: Screening for tuberculosis prior to highly active antiretroviral therapy (HAART) initiation is not routinely performed in low-incidence settings. Identifying factors associated with developing tuberculosis after HAART initiation could focus screening efforts. METHODS: Sixteen cohorts in the United States and Canada contributed data on persons infected with human immunodeficiency virus (HIV) who initiated HAART December 1995-August 2009. Parametric survival models identified factors associated with tuberculosis occurrence. RESULTS: Of 37845 persons in the study, 145 were diagnosed with tuberculosis after HAART initiation. Tuberculosis risk was highest in the first 3 months of HAART (20 cases; 215 cases per 100000 person-years; 95% confidence interval [CI]: 131-333 per 100000 person-years). In a multivariate Weibull proportional hazards model, baseline CD4+ lymphocyte count <200, black race, other nonwhite race, Hispanic ethnicity, and history of injection drug use were independently associated with tuberculosis risk. In addition, in a piece-wise Weibull model, increased baseline HIV-1 RNA was associated with increased tuberculosis risk in the first 3 months; male sex tended to be associated with increased risk. CONCLUSIONS: Screening for active tuberculosis prior to HAART initiation should be targeted to persons with baseline CD4 <200 lymphocytes/mm³ or increased HIV-1 RNA, persons of nonwhite race or Hispanic ethnicity, history of injection drug use, and possibly male sex.
Trends in Multidrug Treatment Failure and Subsequent Mortality among Antiretroviral Therapy-Experienced Patients with HIV Infection in North America
Background. Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined.Methods. Sixteen cohorts representing over 60 sites contributed data on all individuals who initiated combination antiretroviral therapy. We identified those individuals who experienced virologic failure (defined as a human immunodeficiency virus [HIV] RNA level 1000 copies/mL), received modified therapy, and subsequently had a second episode of virologic failure. Multivariate Cox regression was used to assess factors associated with time to second regimen failure and the time to death after the onset of second regimen failure.Results. Of the 42,790 individuals who received therapy, 7159 experienced a second virologic failure. The risk of second virologic failure decreased from 1996 (56 cases per 100 person-years) through 2005 (16 cases per 100 person-years; P.001). The cumulative mortality after onset of second virologic failure was 26\% at 5 years and decreased over time. A history of AIDS, a lower CD4+T cell count, and a higher plasma HIV RNA level were each independently associated with mortality. Similar trends were observed when analysis was limited to the subset of previously treatment-naive patientsConclusions. Although the rates of multiple regimen failure have decreased dramatically over the past decade, mortality rates for those who have experienced failure of at least 2 regimens have remained high. Plasma HIV RNA levels, CD4+T cell counts at time of treatment failure, and a history of AIDS remain independent risk factors for death, which emphasizes that these factors remain important targets for those in need of more-aggressive therapeutic interventions.
HIV-1 Drug Resistance Mutations Among Antiretroviral-Naive HIV-1 - Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study
HIV-1 Drug Resistance Mutations Among Antiretroviral-Naive HIV-1–Infected Patients in Asia: Results From the TREAT Asia Studies to Evaluate Resistance-Monitoring Study
AIDS-defining illness diagnosed within 90 days after starting highly active antiretroviral therapy among patients from the TREAT Asia HIV Observational Database
Using data from TREAT Asia HIV Observational Database (TAHOD), this paper aims to assess the rate of, and factors associated with the diagnosis of new AIDS-defining illness (ADI) within 90 days after antiretroviral treatment. Patients starting three or more antiretroviral combinations and having subsequent follow-up were included. New ADI cases were checked for evidence of immune reconstitution syndrome (IRS). Among the 1185 patients included, 75 (6.3\%) were diagnosed with a new ADI within 90 days, giving a rate of 26.8/100 person-years, compared with a further 3.6\% cumulative incidence of new ADI between 90 days to one year (4.2/100 person-years). Of the 75 patients, 21 were judged as definitive or presumptive IRS, giving a rate of 7.3/100 person-years. Patients with new ADI generally had lower CD4 counts before treatment started (median, 43 cells/microL). Lower CD4 count, lower body mass index and starting treatment in the same year as the first HIV-positive test done were associated with developing a new ADI. The higher rate of new ADI within 90 days may be partly explained by IRS occurring shortly after treatment. Although it is difficult to identify IRS from observational data, it appears that in TAHOD setting IRS was relatively uncommon.
Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand
Objectives: To evaluate the prevalence and risk factors of anal squamous intraepithelial lesions (ASIL), the putative anal cancer precursor, in Asian HIV positive and HIV negative men who have sex with men (MSM).Methods: Men who underwent anal Pap smear reported clinical, sociodemographic and behavioural information collected through questionnaire and interview between January 2007 and April 2008. χ2 and logistic regression were used to evaluate ASIL prevalence and risk factors among HIV positive and HIV negative MSM.Results: Of the 174 MSM (mean age 32.1 years), 118 (67.8\%) were HIV positive. Overall, 27\% had abnormal anal cytology: 13.2\% had atypical squamous cells of undetermined significance (ASC-US), 11.5\% had low-grade squamous intraepithelial lesion (LSIL) and 2.3\% had high-grade squamous intraepithelial lesion (HSIL). Prevalence of ASIL was higher among HIV positive than HIV negative MSM (33.9\% vs 12.5\%; p = 0.003). Among HIV positive MSM, 16.1\% had ASC-US, 14.4\% had LSIL and 3.4\% had HSIL and 7.1\%, 5.4\% and 0\% in HIV negative MSM, respectively. Anal condyloma was detected in 22\% of HIV positive and 16.1\% (9/56) of HIV negative MSM (p = 0.5). In HIV positive MSM, anal condyloma (OR 3.42, 95\% CI 1.29 to 9.04; p = 0.01) was a significant risk factor for ASIL. Highly active antiretroviral therapy use and CD4+ T cell count were not associated with ASIL.Conclusions: One-third of HIV positive and 12.5\% of HIV negative MSM had ASIL. Thus, as greater numbers of HIV positive MSM live longer due to increasing access to HAART worldwide, effective strategies to screen and manage anal precancerous lesions are needed.
The OpenMRS Implementers Network
OBJECTIVE OpenMRS (www.openmrs.org) is a configurable open source electronic medical record application developed and maintained by a large network of open source developers coordinated by the Regenstrief Institute and Partners in Health and mainly used for HIV patient and treatment information management in Africa. Our objective is to develop an open Implementers Network for OpenMRS to provide regional support for the growing number of OpenMRS implementations in Africa and to include African developers and implementers in the future growth of OpenMRS. METHODS We have developed the OpenMRS Implementers Network using a dedicated Wiki site and e-mail server. We have also organized annual meetings in South Africa and regional training courses at African locations where OpenMRS is being implemented. An OpenMRS Internship program has been initiated and we have started collaborating with similar networks and projects working in Africa. To evaluate its potential, OpenMRS was implemented initially at one site in South Africa by a single implementer using a downloadable OpenMRS application and only the OpenMRS Implementers Network for support. RESULTS The OpenMRS Implementers Network Wiki and list server have grown into effective means of providing implementation support and forums for exchange of implementation experiences. The annual OpenMRS Implementers meeting has been held in South Africa for the past three years and is attracting successively larger numbers of participants with almost 200 implementers and developers attending the 2008 meeting in Durban, South Africa. Six African developers are presently registered on the first intake of the OpenMRS Internship program. Successful collaborations have been started with several African developer groups and projects initiated to develop interoperability between OpenMRS and various applications. The South African OpenMRS Implementer group successfully configured, installed and maintained an integrated HIV/TB OpenMRS application without significant programming support. Since then, this model has been replicated in several other African sites. The OpenMRS Implementers Network has contributed substantially to the growth and sustainability of OpenMRS in Africa and has become a useful way of including Africans in the development and implementation of OpenMRS in developing countries. The Network provides valuable support and enables a basic OpenMRS application to be implemented in the absence of onsite programmers.
Patterns of care in two HIV continuity clinics in Uganda, Africa: a time-motion study
The study objectives were to identify opportunities to improve the quality of care in resource-limited settings by examining the workflow and patient activities at two large outpatient HIV clinics in Uganda. Using time motion study techniques, we collected detailed data on all activities of patients and clinicians in two government-sponsored HIV clinics in Uganda. Processes measured included amount of time clinicians (physicians, nurse practitioners and clinical officers) spend in clinic, the daily patient census and patient visit-length. We also recorded the time spent on various activities by providers and patients. We found that the mean time in clinic per workday at Masaka was 5.5 hours and at Mbarara 4.9 hours, with about 60\% of this time spent in direct and indirect care of patients at both sites. Workday start-times varied by two hours in Masaka and one-and-a half hours in Mbarara and end-times by five and three hours respectively. One-hundred-and-nineteen patients (SD 34) visited Masaka each day and 107 (SD 45) visited Mbarara. The mean duration of the patient visit was 77 minutes at Masaka and 196 minutes at Mbarara, with 66\% and 62\% of the time spent at respective sites waiting for care. We conclude that clinicians in resource-poor settings spend limited amounts of time at the clinic site, with a large portion of the clinic-time taken up by tasks that do not require specialized patient-care skills. This study demonstrates that opportunities exist to improve clinic productivity and visit experience for patients, and provides a baseline for designing and evaluating the impact of process improvement interventions.
Retrospective analysis of the efficacy of gemcitabine for previously treated AIDS-associated Kaposi's sarcoma in western Kenya
OBJECTIVES Evaluation of outcomes in the use of single-agent gemcitabine for the treatment of AIDS-associated Kaposi's sarcoma (KS) in a western Kenyan cancer treatment program. METHODS Retrospective chart review of all patients with KS treated with single agent gemcitabine following failure of first-line Adriamycin, bleomycin, and vincristine (ABV). Baseline demographics were collected, and clinicians' assessments of response were utilized to fill out objective criteria for both response as well as symptom benefit assessment. RESULTS Twenty-three patients with KS who had previously failed first-line therapy with ABV were evaluated. Following treatment, 22 of the 23 patients responded positively to treatment with stable disease or better. Of the 18 patients who had completed therapy, with a median follow-up of 5 months, 12 patients had no documented progression. CONCLUSIONS Treatment options in the resource-constrained setting are limited, both by financial constraints as well as the need to avoid myelotoxicity, which is associated with high morbidity in this treatment setting. This work shows that gemcitabine has promising activity in KS, with both objective responses and clinical benefit observed in this care setting. Gemcitabine as a single agent merits further investigation for AIDS-associated KS.
The clinical burden of tuberculosis among human immunodeficiency virus-infected children in Western Kenya and the impact of combination antiretroviral treatment
CONTEXT The burden of tuberculosis (TB) disease in children, particularly in HIV-infected children, is poorly described because of a lack of effective diagnostic tests and the emphasis of public health programs on transmissible TB. OBJECTIVES The objectives of this study were to describe the observed incidence of and risk factors for TB diagnosis among HIV-infected children enrolled in a large network of HIV clinics in western Kenya. DESIGN Retrospective observational study. SETTING The USAID-Academic Model Providing Access to Healthcare (AMPATH) Partnership is Kenya's largest HIV/AIDS care system. Since 2001, the program has enrolled over 70,000 HIV-infected patients in 18 clinics throughout Western Kenya. PATIENTS This analysis included all HIV-infected children aged 0 to 13 years attending an AMPATH clinic. MAIN OUTCOME MEASURE The primary outcome was a diagnosis of any TB, defined either by a recorded diagnosis or by the initiation of anti-TB treatment. Diagnosis of TB is based on a modified Kenneth Jones scoring system and is consistent with WHO case definitions. RESULTS There were 6535 HIV-infected children aged 0 to 13 years, eligible for analysis, 50.1\% were female. Of these, 234 (3.6\%) were diagnosed with TB at enrollment. There were subsequently 765 new TB diagnoses in 4368.0 child-years of follow-up for an incidence rate of 17.5 diagnoses (16.3-18.8) per 100 child-years. The majority of these occurred in the first 6 months after enrollment (IR: 106.8 per 100 CY, 98.4-115.8). In multivariable analysis, being severely immune-suppressed at enrollment (Adjusted Hazard Ratio [AHR]: 4.44, 95\% CI: 3.62-5.44), having ever attended school AHR: 2.65, 95\% CI: 2.15-3.25), being an orphan (AHR: 1.57, 95\% CI: 1.28-1.92), being severely low weight-for-height at enrollment (AHR: 1.46, 95\% CI: 1.32-1.62), and attending an urban clinic (AHR: 1.39, 95\% CI: 1.16-1.67) were all independent risk factors for having an incident TB diagnosis. Children receiving combination antiretroviral treatment were dramatically less likely to be diagnosed with incident TB (AHR: 0.15, 95\% CI: 0.12-0.20). CONCLUSIONS These data suggest a high rate of TB diagnosis among HIV-infected children, with severe immune suppression, school attendance, orphan status, very low weight-for-height, and attending an urban clinic being key risk factors. The use of combination antiretroviral treatment reduced the probability of an HIV-infected child being diagnosed with incident TB by 85\%.
Evaluating a scalable model for implementing electronic health records in resource-limited settings
Current models for implementing electronic health records (EHRs) in resource-limited settings may not be scalable because they fail to address human-resource and cost constraints. This paper describes an implementation model which relies on shared responsibility between local sites and an external three-pronged support infrastructure consisting of: (1) a national technical expertise center, (2) an implementer's community, and (3) a developer's community. This model was used to implement an open-source EHR in three Ugandan HIV-clinics. Pre-post time-motion study at one site revealed that Primary Care Providers spent a third less time in direct and indirect care of patients (p0.001) and 40\% more time on personal activities (p=0.09) after EHRs implementation. Time spent by previously enrolled patients with non-clinician staff fell by half (p=0.004) and with pharmacy by 63\% (p0.001). Surveyed providers were highly satisfied with the EHRs and its support infrastructure. This model offers a viable approach for broadly implementing EHRs in resource-limited settings.
Late-disease stage at presentation to an HIV clinic in the era of free antiretroviral therapy in Sub-Saharan Africa
BACKGROUND Access to free antiretroviral therapy in sub-Saharan Africa has been steadily increasing, and the success of large-scale antiretroviral therapy programs depends on early initiation of HIV care. However, little is known about the stage at which those infected with HIV present for treatment in sub-Saharan Africa. METHODS We conducted a cross-sectional analysis of initial visits to the Immune Suppression Syndrome Clinic of the Mbarara University Teaching Hospital, including patients who had their initial visit between February 2007 and February 2008 (N = 2311). RESULTS The median age of the patients was 33 years (range 16-81 years), and 64\% were female. More than one third (40\%) were categorized as late presenters, that is, World Health Organization disease stage 3 or 4. Male gender, age 46-60 years (vs. younger), lower education level, being unemployed, living in a household with others, being unmarried, and lack of spousal HIV status disclosure were independently associated with late presentation, whereas being pregnant, having young children, and consuming alcohol in the prior year were associated with early presentation. CONCLUSIONS Targeted public health interventions to facilitate earlier entry into HIV care are needed, as well as additional study to determine whether late presentation is due to delays in testing vs. delays in accessing care.
Understanding reasons for and outcomes of patients lost to follow-up in antiretroviral therapy programs in Africa through a sampling-based approach
OBJECTIVES Losses to follow-up after initiation of antiretroviral therapy (ART) are common in Africa and are a considerable obstacle to understanding the effectiveness of nascent treatment programs. We sought to characterize, through a sampling-based approach, reasons for and outcomes of patients who become lost to follow-up. DESIGN Cohort study. METHODS We searched for and interviewed a representative sample of lost patients or close informants in the community to determine reasons for and outcomes among lost patients. RESULTS Three thousand six hundred twenty-eight HIV-infected adults initiated ART between January 1, 2004 and September 30, 2007 in Mbarara, Uganda. Eight hundred twenty-nine became lost to follow-up (cumulative incidence at 1, 2, and 3 years of 16\%, 30\%, and 39\%). We sought a representative sample of 128 lost patients in the community and ascertained vital status in 111 (87\%). Top reasons for loss included lack of transportation or money and work/child care responsibilities. Among the 111 lost patients who had their vital status ascertained through tracking, 32 deaths occurred (cumulative 1-year incidence 36\%); mortality was highest shortly after the last clinic visit. Lower pre-ART CD4 T-cell count, older age, low blood pressure, and a central nervous system syndrome at the last clinic visit predicted deaths. Of patients directly interviewed, 83\% were in care at another clinic and 71\% were still using ART. CONCLUSIONS Sociostructural factors are the primary reasons for loss to follow-up. Outcomes among the lost are heterogeneous: both deaths and transfers to other clinics were common. Tracking a sample of lost patients is an efficient means for programs to understand site-specific reasons for and outcomes among patients lost to follow-up.
Diminishing availability of publicly funded slots for antiretroviral initiation among HIV-infected ART-eligible patients in Uganda
BACKGROUND The impact of flat-line funding in the global scale up of antiretroviral therapy (ART) for HIV-infected patients in Africa has not yet been well described. METHODS We evaluated ART-eligible patients and patients starting ART at a prototypical scale up ART clinic in Mbarara, Uganda between April 1, 2009 and May 14, 2010 where four stakeholders sponsor treatment - two PEPFAR implementing organizations, the Ugandan Ministry of Health - Global Fund (MOH-GF) and a private foundation named the Family Treatment Fund (FTF). We assessed temporal trends in the number of eligible patients, the number starting ART and tabulated the distribution of the stakeholders supporting ART initiation by month and quartile of time during this interval. We used survival analyses to assess changes in the rate of ART initiation over calendar time. FINDINGS A total of 1309 patients who were eligible for ART made visits over the 14 month period of the study and of these 819 started ART. The median number of ART eligible patients each month was 88 (IQR: 74 to 115). By quartile of calendar time, PEPFAR and MOH sponsored 290, 192, 180, and 49 ART initiations whereas the FTF started 1, 2, 1 and 104 patients respectively. By May of 2010 (the last calendar month of observation) FTF sponsored 88\% of all ART initiations. Becoming eligible for ART in the 3(rd) (HR = 0.58, 95\% 0.45-0.74) and 4(th) quartiles (HR = 0.49, 95\% CI: 0.36-0.65) was associated with delay in ART initiation compared to the first quartile in multivariable analyses. INTERPRETATION During a period of flat line funding from multinational donors for ART programs, reductions in the number of ART initiations by public programs (i.e., PEPFAR and MOH-GF) and delays in ART initiation became apparent at the a large prototypical scale-up ART clinic in Uganda.
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; p0.001) and WHO stage 3-4 disease (47.5\% versus 41.1\%; p0.001). Urban clinic clients were 75.0\% of non-dropouts but 70.3\% of dropouts (p0.001). 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.