Elvin Geng

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.

Sampling-based approach to determining outcomes of patients lost to follow-up in antiretroviral therapy scale-up programs in Africa.

Evaluating outcomes among the millions of HIV-infected patients starting antiretroviral therapy (ART) in settings with limited resources is key to understanding the effect of current treatment programs and guiding future strategies. Accurately assessing survival outcomes has been precluded by substantial numbers of patients not returning for care. One year after starting ART 15% to 30% of patients are lost to follow-up. Only by determining the outcomes of those lost can true survival and program impact be understood. We present a sampling-based strategy to address this. (excerpt)

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.

Correcting Mortality for Loss to Follow-Up: A Nomogram Applied to Antiretroviral Treatment Programmes in Sub-Saharan Africa

Matthias Egger and colleagues present a nomogram and a web-based calculator to correct estimates of program-level mortality for loss to follow-up, for use in antiretroviral treatment programs.

Toward an understanding of disengagement from HIV treatment and care in sub-Saharan Africa: a qualitative study.

Norma Ware and colleagues conducted a large qualitative study among patients in HIV treatment programs in sub-Saharan Africa to investigate reasons for missed visits and provide an explanation for disengagement from care.

Leveraging rapid community-based hiv testing campaigns for non-communicable diseases in rural uganda

Background The high burden of undiagnosed HIV in sub-Saharan Africa limits treatment and prevention efforts. Community-based HIV testing campaigns can address this challenge and provide an untapped opportunity to identify non-communicable diseases (NCDs). We tested the feasibility and diagnostic yield of integrating NCD and communicable diseases into a rapid HIV testing and referral campaign for all residents of a rural Ugandan parish. Methods A five-day, multi-disease campaign, offering diagnostic, preventive, treatment and referral services, was performed in May 2011. Services included point-of-care screening for HIV, malaria, TB, hypertension and diabetes. Finger-prick diagnostics eliminated the need for phlebotomy. HIV-infected adults met clinic staff and peer counselors on-site; those with CD4≤100/µL underwent intensive counseling and rapid referral for antiretroviral therapy (ART). Community participation, case-finding yield, and linkage to care three months post-campaign were analyzed. Results Of 6,300 residents, 2,323/3,150 (74%) adults and 2,020/3,150 (69%) children participated. An estimated 95% and 52% of adult female and male residents participated respectively. Adult HIV prevalence was 7.8%, with 46% of HIV-infected adults newly diagnosed. Thirty-nine percent of new HIV diagnoses linked to care. In a pilot subgroup with CD4≤100, 83% linked and started ART within 10 days. Malaria was identified in 10% of children, and hypertension and diabetes in 28% and 3.5% of adults screened, respectively. Sixty-five percent of hypertensives and 23% of diabetics were new diagnoses, of which 43% and 61% linked to care, respectively. Screening identified suspected TB in 87% of HIV-infected and 19% of HIV-uninfected adults; 52% percent of HIV-uninfected TB suspects linked to care. Conclusions In an integrated campaign engaging 74% of adult residents, we identified a high burden of undiagnosed HIV, hypertension and diabetes. Improving male attendance and optimizing linkage to care require new approaches. The campaign demonstrates the feasibility of integrating hypertension, diabetes and communicable diseases into HIV initiatives.

Failure to Initiate Antiretroviral Therapy, Loss to Follow-up and Mortality among HIV-infected Patients during the Pre-ART period in Uganda

Background:Delays and failures in initiation of antiretroviral therapy (ART) among treatment eligible patients may compromise the effectiveness of HIV care in Africa. An accurate understanding, however, of the pace and completeness of ART initiation and mortality during the waiting period is obscured by frequent losses to follow-up. Methods:We evaluated newly ART-eligible HIV-infected adults from 2007 to 2011 in a prototypical clinic in Mbarara, Uganda. A random sample of patients lost to follow-up was tracked in the community to determine vital status and ART initiation after leaving the original clinic. Outcomes among the tracked patients were incorporated using probability weights, and a competing risks approach was used in analyses. Results:Among 2633 ART-eligible patients, 490 were lost to follow-up, of whom a random sample of 132 was tracked and 111 (84.0%) had outcomes ascertained. After incorporating the outcomes among the lost, the cumulative incidence of ART initiation at 30, 90, and 365 days after eligibility was 16.0% [95% confidence interval (CI): 14.2 to 17.7], 64.5% (95% CI: 60.9 to 68.1), and 81.7% (95% CI: 77.7 to 85.6). Death before ART was 7.7% at 1 year. Male sex, higher CD4 count, and no education were associated with delayed ART initiation. Lower CD4 level, malnourishment, and travel time to clinic were associated with mortality. Conclusions:Using a sampling-based approach to account for losses to follow-up revealed that both the speed and the completeness of ART initiation were suboptimal in a prototypical large clinic in Uganda. Improving the kinetics of ART initiation in Africa is needed to make ART more in real-world populations.

Rethinking the "pre" in pre-therapy counseling: No benefit of additional visits prior to therapy on adherence or Viremia in Ugandans initiating ARVs

Background Many guidelines recommend adherence counseling prior to initiating antiretrovirals (ARVs), however the additional benefit of pre-therapy counseling visits on early adherence is not known. We sought to assess for a benefit of adherence counseling visits prior to ARV initiation versus adherence counseling during the early treatment period. Methods We performed a secondary analysis of data from a prospective cohort of HIV-infected patients in Mbarara, Uganda. Adults were enrolled upon initiation of ARVs. Our primary exposure of interest was ARV adherence counseling prior to initiating therapy (versus concurrent with initiation of therapy). Our outcomes of interest were: 1) average adherence >90% in first three months; 2) absence of treatment interruptions >72 hours in first three months; and 3) Viral load >400 copies/ml at the three month visit. We fit univariable and multivariable regression models, adjusted for predictors of ARV adherence, to estimate the association between additional pre-therapy counseling visits and our outcomes. Results 300 participants had records of counseling, of whom 231 (77%) completed visits prior to initiation of ARVs and 69 (23%) on or shortly after initiation. Median age was 33, 71% were female, and median CD4 was 133 cell/ml. Median 90-day adherence was 95%. Participants who completed pre-therapy counseling visits had longer delays from ARV eligibility to initiation (median 49 vs 14 days, p<0.01). In multivariable analyses, completing adherence counseling prior to ARV initiation was not associated with average adherence >90% (AOR 0.8, 95%CI 0.4–1.5), absence of treatment gaps (AOR 0.7, 95%CI 0.2–1.9), or HIV viremia (AOR 1.1, 95%CI 0.4–3.1). Conclusions Completion of adherence counseling visits prior to ARV therapy was not associated with higher adherence in this cohort of HIV-infected patients in Uganda. Because mortality and loss-to-follow-up remain high in the pre-ARV period, policy makers should reconsider whether counseling can be delivered with ARV initiation, especially in patients with advanced disease.

Retention in care and connection to care among HIV-infected patients on antiretroviral therapy in Africa: Estimation via a Sampling-Based approach

Introduction Current estimates of retention among HIV-infected patients on antiretroviral therapy (ART) in Africa consider patients who are lost to follow-up (LTF) as well as those who die shortly after their last clinic visit to be no longer in care and to represent limitations in access to care. Yet many lost patients may have “silently” transferred and deaths shortly after the last clinic visit more likely represent limitations in clinical care rather than access to care after initial linkage. Methods We evaluated HIV-infected adults initiating ART from 1/1/2004 to 9/30/2007 at a clinic in rural Uganda. A representative sample of lost patients was tracked in the community to obtain updated information about care at other ART sites. Updated outcomes were incorporated with probability weights to obtain “corrected” estimates of retention for the entire clinic population. We used the competing risks approach to estimate “connection to care”—the percentage of patients accessing care over time (including those who died while in care). Results Among 3,628 patients, 829 became lost, 128 were tracked and in 111, updated information was obtained. Of 111, 79 (71%) were alive and 35/48 (73%) of patients interviewed in person were in care and on ART. Patient retention for the clinic population assuming lost patients were not in care was 82.3%, 68.9%, and 60.1% at 1, 2 and 3 years. Incorporating updated care information from the sample of lost patients increased estimates of patient retention to 85.8% to 90.9%, 78.9% to 86.2% and 75.8% to 84.7% at the same time points. Conclusions Accounting for “silent transfers” and early deaths increased estimates of patient retention and connection to care substantially. Deaths soon after the last clinic visit (potentially reflecting limitations in clinical effectiveness) and disconnection from care among patient who were alive each accounted for approximately half of failures of retention.

Beyond Core Indicators of Retention in HIV Care: Missed Clinic Visits Are Independently Associated With All-Cause Mortality

BACKGROUND The continuum of care is at the forefront of the domestic human immunodeficiency virus (HIV) agenda, with the Institute of Medicine (IOM) and Department of Health and Human Services (DHHS) recently releasing clinical core indicators. Core indicators for retention in care are calculated based on attended HIV care clinic visits. Beyond these retention core indicators, we evaluated the additional prognostic value of missed clinic visits for all-cause mortality. METHODS We conducted a multisite cohort study of 3672 antiretroviral-naive patients initiating antiretroviral therapy (ART) during 2000-2010. Retention in care was measured by the IOM and DHHS core indicators (2 attended visits at defined intervals per 12-month period), and also as a count of missed primary HIV care visits (no show) during a 24-month measurement period following ART initiation. All-cause mortality was ascertained by query of the Social Security Death Index and/or National Death Index, with adjusted survival analyses starting at 24 months after ART initiation. RESULTS Among participants, 64% and 59% met the IOM and DHHS retention core indicators, respectively, at 24 months. Subsequently, 332 patients died during 16 102 person-years of follow-up. Failure to achieve the IOM and DHHS indicators through 24 months following ART initiation increased mortality (hazard ratio [HR] = 2.23; 95% confidence interval [CI], 1.79-2.80 and HR = 2.36; 95% CI, 1.89-2.96, respectively). Among patients classified as retained by the IOM or DHHS clinical core indicators, >2 missed visits further increased mortality risk (HR = 3.61; 95% CI, 2.35-5.55 and HR = 3.62; 95% CI, 2.30-5.68, respectively). CONCLUSIONS Beyond HIV retention core indicators, missed clinic visits were independently associated with all-cause mortality. Caution is warranted in relying solely upon retention in care core indicators for policy, clinical, and programmatic purposes.