Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa

Objective. To identify predictors of mortality in patients initiating antiretroviral therapy (ART) in Durban, South Africa. Design. We conducted a retrospective cohort study analysing data on patients who presented to McCord Hospital, Durban, and started ART between 1 January 1999 and 29 February 2004. We performed univariate and multivariate analysis and constructed Kaplan-Meier curves to assess predictors. Results. Three hundred and nine patients were included. Forty-nine (16%) had died by the conclusion of the study. In univariate analysis, the strongest predictors of mortality were a CD4 cell coun

The Survival Benefits of Antiretroviral Therapy in South Africa

Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa

HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

Background: We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods: We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results: For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10$54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At$150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions: Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV

Clinical Impact and Cost-Effectiveness of Expanded Voluntary HIV Testing in India

Background: Despite expanding access to antiretroviral therapy (ART), most of the estimated 2.3 to 2.5 million HIV-infected individuals in India remain undiagnosed. The questions of whom to test for HIV and at what frequency remain unclear. Methods: We used a simulation model of HIV testing and treatment to examine alternative HIV screening strategies: 1) current practice, 2) one-time, 3) every five years, and 4) annually; and we applied these strategies to three population scenarios: 1) the general Indian population (“national population”), i.e. base case (HIV prevalence 0.29%; incidence 0.032/100 person-years [PY]); 2) high-prevalence districts (HIV prevalence 0.8%; incidence 0.088/100 PY), and 3) high-risk groups (HIV prevalence 5.0%; incidence 0.552/100 PY). Cohort characteristics reflected Indians reporting for HIV testing, with a median age of 35 years, 66% men, and a mean CD4 count of 305 cells/µl. The cost of a rapid HIV test was $3.33. Outcomes included life expectancy, HIV-related direct medical costs, incremental cost-effectiveness ratios (ICERs), and secondary transmission benefits. The threshold for “cost-effective” was defined as 3x the annual per capita GDP of India ($3,900/year of life saved [YLS]), or for “very cost-effective” was <1x the annual per capita GDP ($1,300/YLS). Results: Compared to current practice, one-time screening was very cost-effective in the national population (ICER:$1,100/YLS), high-prevalence districts (ICER: $800/YLS), and high-risk groups (ICER:$800/YLS). Screening every five years in the national population (ICER: $1,900/YLS) and annual screening in high-prevalence districts (ICER:$1,900/YLS) and high-risk groups (ICER: $1,800/YLS) were also cost-effective. Results were most sensitive to costs of care and linkage-to-care. Conclusions: In India, voluntary HIV screening of the national population every five years offers substantial clinical benefit and is cost-effective. Annual screening is cost-effective among high-risk groups and in high-prevalence districts nationally. Routine HIV screening in India should be implemented

The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort.

HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients

Climate and predation dominate juvenile and adult recruitment in a turtle with temperature-dependent sex determination

Conditions experienced early in life can influence phenotypes in ecologically important ways, as exemplified by organisms with environmental sex determination. For organisms with temperature-dependent sex determination (TSD), variation in nest temperatures induces phenotypic variation that could impact population growth rates. In environments that vary over space and time, how does this variation influence key demographic parameters (cohort sex ratio and hatchling recruitment) in early life stages of populations exhibiting TSD? We leverage a 17-year data set on a population of painted turtles, Chrysemys picta, to investigate how spatial variation in nest vegetation cover and temporal variation in climate influence early life-history demography. We found that spatial variation in nest cover strongly influenced nest temperature and sex ratio, but was not correlated with clutch size, nest predation, total nest failure, or hatching success. Temporal variation in climate influenced percentage of total nest failure and cohort sex ratio, but not depredation rate, mean clutch size, or mean hatching success. Total hatchling recruitment in a year was influenced primarily by temporal variation in climate-independent factors, number of nests constructed, and depredation rate. Recruitment of female hatchlings was determined by stochastic variation in nest depredation and annual climate and also by the total nest production. Overall population demography depends more strongly on annual variation in climate and predation than it does on the intricacies of nest-specific biology. Finally, we demonstrate that recruitment of female hatchlings translates into recruitment of breeding females into the population, thus linking climate (and other) effects on early life stages to adult demographics

Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa

Abstract Background: Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality. Methods: We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality. Results: Among 726 HIV-infected adults with median CD4 of 205 cells/mm3 (interquartile range, 79–350 cells/mm3), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20–5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26–6.73) MHR for all participants and a 4.55 (95% CI, 1.71–12.1) MHR for participants with CD4 ≤100 cell/mm3. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease. Conclusions: Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative

What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured

What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured