Incidence and Predictors of Death, Retention, and Switch to Second-Line Regimens in Antiretroviral-Treated Patients in Sub-Saharan African Sites with Comprehensive Monitoring Availability
ABSTRACT Antiretroviral treatment programs in sub-Saharan Africa have high rates of early mortality and loss to follow-up. Switching to second-line regimens is often delayed because of limited access to laboratory monitoring.
Retrospective analysis was performed of a cohort of adults who initiated a standard first-line antiretroviral treatment at 5 public sector sites in 3 African countries. Monitoring included routine CD4 cell counts, human immunodeficiency virus RNA measures, and records of whether appointments were kept. Incidence and predictors of death, loss to follow-up, and switch to second-line regimens were analyzed by time-to-event approaches.
A total of 3749 patients were analyzed; at baseline, 37.1% were classified as having World Health Organization disease stage 3 or 4, and the median CD4 cell count was 192 cells/mL. First-line regimens were nevirapine based in 96.5% of patients; 17.7% of patients attended <95% of their drug pickup appointments. During 4545 person-years of follow-up, mortality was 8.6 deaths per 100 person-years and was predicted by lower baseline CD4 cell count, lower hemoglobin level, and lower body mass index (calculated as weight in kilograms divided by the square of height in meters); more-advanced clinical stage of infection; male sex; and more missed drug pickup appointments. Dropouts (which accrued at a rate of 2.1 dropouts per 100 person-years) were predicted by a lower body mass index, more missed visits and missed drug pickup appointments, and later calendar year. Incidence of switches to second-line regimens was 4.9 per 100 person-years; increased hazards were observed with lower CD4 cell count and earlier calendar year at baseline. In patients who switched, virological failure was predicted by combined clinical and CD4 criteria with 74% sensitivity and 30% specificity.
In an antiretroviral treatment program employing comprehensive monitoring, the probability of switching to second-line therapy was limited. Regular pickup of medication was a predictor of survival and was also strongly predictive of patient retention.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods.Journal of the International AIDS Society 01/2015; 18(1):19463. · 4.21 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: In resource constrained settings, immunological assessment through CD4 count is used to assess response to first line Highly Active Antiretroviral Therapy (HAART). In this study, we aim to investigate factors associated with immunological treatment failure. A matched case-control study design was used. Cases were subjects who already experienced immunological treatment failure and controls were those without immunological failure after an exactly or approximately equivalent duration of first line treatment with cases. Data were analyzed using SPSS v16.0. Conditional logistic regression was carried out. A total of 134 cases and 134 controls were included in the study. At baseline, the mean age ±1 SD of cases was 37.5±9.7 years whereas it was 36.9±9.2 years among controls. The median baseline CD4 counts of cases and controls were 121.0 cells/µl (IQR: 47-183 cells/µl) and 122.0 cells/µl (IQR: 80.0-189.8 cells/µl), respectively. The median rate of CD4 cells increase was comparable for the two groups in the first six months of commencing HAART (P = 0.442). However, the median rate of CD4 increase was significantly different for the two groups in the next 6 months period (M6 to M12). The rate of increment was 8.8 (IQR: 0.5, 14.6) and 1.8 (IQR: 8.8, 11.3) cells/µl/month for controls and cases, respectively (Mann-Whitney U test, P = 0.003). In conditional logistic regressions grouped baseline CD4 count (P = 0.028), old age group and higher educational status (P<0.001) were significant predictors of immunological treatment failure. Subjects with immunological treatment failure have an optimal rate of immunological recovery in the first 6 months of treatment with first line HAART, but relative to the non-failing group the rate declines at a later period, notably between 6 and 12 months. Low baseline CD4 count, old age and higher educational status were associated with immunological treatment failure.PLoS ONE 12/2014; 9(12):e115125. DOI:10.1371/journal.pone.0115125 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The Academic Model Providing Access To Healthcare (AMPATH) program provides comprehensive HIV care and treatment services. Approximately 30% of patients have become lost to follow-up (LTFU). We sought to actively trace and identify outcomes for a sample of these patients. LTFU was defined as missing a scheduled visit by ≥ 3 months. A randomly selected sample of 17% of patients identified as LTFU between January 2009 and June 2011 was generated, with sample stratification on age, antiretroviral therapy (ART) status at last visit, and facility. Chart reviews were conducted followed by active tracing. Tracing was completed by trained HIV-positive outreach workers July 2011 to February 2012. Outcomes were compared between adults and children and by ART status. Of 14,811 LTFU patients, 2,540 were randomly selected for tracing (2,179 adults, 1,071 on ART). The chart reviews indicated that 326 (12.8%) patients were not actually LTFU. Outcomes for 71% of sampled patients were determined including 85% of those physically traced. Of those with known outcomes, 21% had died while 29% had disengaged from care for various reasons. The remaining patients had moved away (n=458, 25%) or were still receiving HIV care (n=443 total, 25%). Our findings demonstrate the feasibility of a large scale sampling-based approach. A significant proportion of patients were found not to be LTFU and further, high numbers of patients who were LTFU could not be located. Over a quarter of patients disengaged from care for various reasons including access challenges and familial influences.JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2014; 68(4). DOI:10.1097/QAI.0000000000000492 · 4.39 Impact Factor