T cell subsets in HIV infected patients after successful combination antiretroviral therapy: impact on survival after 12 years

Objectives

Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up.

Methods

A cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was included in 1997–1998. T cell subsets were analyzed by flowcytometry after 18 months of cART. Relation to survival was calculated using Kaplan-Meier curves and multiple Cox regression.

Results

Seventeen patients died during the observation period. The leading causes of death were non-AIDS cancer and cardiovascular disease. Higher levels of CD8 memory T cells (CD8+,CD45RO+,CD45RA-) showed a significant beneficiary effect on survival, HR of 0.95 (95% confidence interval 0.91–0.99, P = 0.016) when adjusted for age, nadir CD4 count, CD4 count, and AIDS and hepatitis C status. T cell activation was not associated with increased risk of death.

Conclusions

Larger and longitudinal studies are needed to accurately establish prognostic factors, but overall results seem to suggest that prognostic information exists within the CD8 compartment.     

Late entry to HIV care limits the impact of anti-retroviral therapy in The Netherlands

Objective

To explain differences in survival in the first three years of combination anti-retroviral therapy (cART) between HIV treatment centres in the Netherlands.

Methodology/Principal Findings

We developed a mathematical simulation model, parameterised using data from the ATHENA cohort that describes patients entering care, being monitored and starting cART. Three scenarios were used to represent three treatment centres with widely varying mortality rates on cART that were differentiated by: (i) the distribution of CD4 counts of patients entering care; (ii) the age distribution of patients entering care; (iii) the average rate of monitoring the patients not on cART. At the level of the treatment centre, the fraction of Dutch MSM dying in the first three years of treatment ranged from 0% to 8%. The mathematical model captured the large variation in observed mortality between the three treatment centres. Manipulating the age-distribution of patients or the frequency of monitoring did not affect the model predictions. In contrast, when the same national average distribution of CD4 count at entry was used in all the scenarios, the variation in predicted mortality between all centres was diminished.

Conclusions/Significance

Patients entering care with low CD4 counts appears to be the main source of variation in the mortality rates between Dutch treatment centres. Recruiting HIV-infected individuals to care earlier could lead to substantial improvements in cART outcomes. For example, if patients were to present with at least 400 CD4 cells/mm³, as they do already in some centres, then our model predicts that the mortality in the first three years of cART could be reduced by approximately 20%.     

Randomized trial of time-limited interruptions of protease inhibitor-based antiretroviral therapy (ART) vs. continuous therapy for HIV-1 infection

Background

The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.

Methods

A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints.

Results

The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm.

Conclusion

We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00100646","term_id":"NCT00100646"}}NCT00100646     

Massage therapy for osteoarthritis of the knee: a randomized dose-finding trial

Background

In a previous trial of massage for osteoarthritis (OA) of the knee, we demonstrated feasibility, safety and possible efficacy, with benefits that persisted at least 8 weeks beyond treatment termination.

Methods

We performed a RCT to identify the optimal dose of massage within an 8-week treatment regimen and to further examine durability of response. Participants were 125 adults with OA of the knee, randomized to one of four 8-week regimens of a standardized Swedish massage regimen (30 or 60 min weekly or biweekly) or to a Usual Care control. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog pain scale, range of motion, and time to walk 50 feet, assessed at baseline, 8-, 16-, and 24-weeks.

Results

WOMAC Global scores improved significantly (24.0 points, 95% CI ranged from 15.3–32.7) in the 60-minute massage groups compared to Usual Care (6.3 points, 95% CI 0.1–12.8) at the primary endpoint of 8-weeks. WOMAC subscales of pain and functionality, as well as the visual analog pain scale also demonstrated significant improvements in the 60-minute doses compared to usual care. No significant differences were seen in range of motion at 8-weeks, and no significant effects were seen in any outcome measure at 24-weeks compared to usual care. A dose-response curve based on WOMAC Global scores shows increasing effect with greater total time of massage, but with a plateau at the 60-minute/week dose.

Conclusion

Given the superior convenience of a once-weekly protocol, cost savings, and consistency with a typical real-world massage protocol, the 60-minute once weekly dose was determined to be optimal, establishing a standard for future trials.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00970008","term_id":"NCT00970008"}}NCT00970008     

Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption

Background

Long-term benefits of combination antiretroviral therapy (cART) initiation during primary HIV-1 infection are debated.

Methods

The evolution of plasma HIV-RNA (432 measurements) and cell-associated HIV-DNA (325 measurements) after cessation of cART (median exposure 18 months) was described for 33 participants from the Zurich Primary HIV Infection Study using linear regression and compared with 545 measurements from 79 untreated controls with clinically diagnosed primary HIV infection, respectively a known date for seroconversion.

Results

On average, early treated individuals were followed for 37 months (median) after cART cessation; controls had 34 months of pre-cART follow-up. HIV-RNA levels one year after cART interruption were −0.8 log₁₀ copies/mL [95% confidence interval −1.2;−0.4] lower in early treated patients compared with controls, but this difference was no longer statistically significant by year three of follow-up (−0.3 [−0.9; 0.3]). Mean HIV-DNA levels rebounded from 2 log₁₀ copies [1.8; 2.3] on cART to a stable plateau of 2.7 log₁₀ copies [2.5; 3.0] attained 1 year after therapy stop, which was not significantly different from cross-sectional measurements of 9 untreated members of the control group (2.8 log₁₀ copies [2.5; 3.1]).

Conclusions

The rebound dynamics of viral markers after therapy cessation suggest that early cART may indeed limit reservoir size of latently infected cells, but that much of the initial benefits are only transient. Owing to the non-randomized study design the observed treatment effects must be interpreted with caution.     

Survival of HIV-infected adolescents on antiretroviral therapy in Uganda: findings from a nationally representative cohort in Uganda

Background

Adolescents have been identified as a high-risk group for poor adherence to and defaulting from combination antiretroviral therapy (cART) care. However, data on outcomes for adolescents on cART in resource-limited settings remain scarce.

Methods

We developed an observational study of patients who started cART at The AIDS Service Organization (TASO) in Uganda between 2004 and 2009. Age was stratified into three groups: children (≤10 years), adolescents (11–19 years), and adults (≥20 years). Kaplan-Meier survival curves were generated to describe time to mortality and loss to follow-up, and Cox regression used to model associations between age and mortality and loss to follow-up. To address loss to follow up, we applied a weighted analysis that assumes 50% of lost patients had died.

Findings

A total of 23,367 patients were included in this analysis, including 810 (3.5%) children, 575 (2.5%) adolescents, and 21 982 (94.0%) adults. A lower percentage of children (5.4%) died during their cART treatment compared to adolescents (8.5%) and adults (10%). After adjusting for confounding, other features predicted mortality than age alone. Mortality was higher among males (p<0.001), patients with a low initial CD4 cell count (p<0.001), patients with advanced WHO clinical disease stage (p<0.001), and shorter duration of time receiving cART (p<0.001). The crude mortality rate was lower for children (22.8 per 1000 person-years; 95% CI: 16.1, 29.5), than adolescents (36.5 per 1000 person-years; 95% CI: 26.3, 46.8) and adults (37.5 per 1000 person-years; 95% CI: 35.9, 39.1).

Interpretation

This study is the largest assessment of adolescents receiving cART in Africa. Adolescents did not have cART mortality outcomes different from adults or children.     

Impact of drug stock-outs on death and retention to care among HIV-infected patients on combination antiretroviral therapy in Abidjan, Côte d'Ivoire

Background

To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Côte d''Ivoire.

Methods and Findings

We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25–6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46–3.16).

Conclusions

cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs.     

Effectiveness of early antiretroviral therapy initiation to improve survival among HIV-infected adults with tuberculosis: a retrospective cohort study

Background

Randomized clinical trials examining the optimal time to initiate combination antiretroviral therapy (cART) in HIV-infected adults with sputum smear-positive tuberculosis (TB) disease have demonstrated improved survival among those who initiate cART earlier during TB treatment. Since these trials incorporated rigorous diagnostic criteria, it is unclear whether these results are generalizable to the vast majority of HIV-infected patients with TB, for whom standard diagnostic tools are unavailable. We aimed to examine whether early cART initiation improved survival among HIV-infected adults who were diagnosed with TB in a clinical setting.

Methods and Findings

We retrospectively reviewed charts for 308 HIV-infected adults in Rwanda with a CD4 count≤350 cells/µl and a TB diagnosis. We estimated the effect of cART on survival using marginal structural models and simulated 2-y survival curves for the cohort under different cART strategies:start cART 15, 30, 60, or 180 d after TB treatment or never start cART. We conducted secondary analyses with composite endpoints of (1) death, default, or lost to follow-up and (2) death, hospitalization, or serious opportunistic infection. Early cART initiation led to a survival benefit that was most marked for individuals with low CD4 counts. For individuals with CD4 counts of 50 or 100 cells/µl, cART initiation at day 15 yielded 2-y survival probabilities of 0.82 (95% confidence interval: [0.76, 0.89]) and 0.86 (95% confidence interval: [0.80, 0.92]), respectively. These were significantly higher than the probabilities computed under later start times. Results were similar for the endpoint of death, hospitalization, or serious opportunistic infection. cART initiation at day 15 versus later times was protective against death, default, or loss to follow-up, regardless of CD4 count. As with any observational study, the validity of these findings assumes that biases from residual confounding by unmeasured factors and from model misspecification are small.

Conclusions

Early cART reduced mortality among individuals with low CD4 counts and improved retention in care, regardless of CD4 count. Please see later in the article for the Editors'' Summary     

The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008

Aim

To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PI_boosted, comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.

Methods

Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).

Results

cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PI_boosted with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685–£12,937) compared with £10,478 (95%CI £10,376–£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).

Conclusion

PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK.     

Survival outcomes and effect of early vs. deferred cART among HIV-infected patients diagnosed at the time of an AIDS-defining event: a cohort analysis

Objectives

We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART).

Methods

Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997–2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (<30 days after AIDS event) or deferred (30–270 days after AIDS event) cART.

Results

The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/µL and 5.2 (4.5, 5.7) log₁₀ copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p = 0.20).

Conclusions

Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting.     

Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion

Objective

Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.

Design

Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.

Methods

Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.

Results

A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).

Conclusions

The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.     

A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy

Background

Immune activation is a strong predictor of disease progression in HIV infection. Combinatorial plasma biomarker signatures that represent surrogate markers of immune activation in both viremic and aviremic HIV patients on combination antiretroviral therapy (cART) have not been defined. Here, we identify a plasma inflammatory biomarker signature that distinguishes between both viremic and aviremic HIV patients on cART and healthy controls and examine relationships of this signature to markers of disease progression.

Methods

Multiplex profiling and ELISA were used to detect 15 cytokines/chemokines, soluble IL-2R (sIL-2R), and soluble CD14 (sCD14) in plasma from 57 HIV patients with CD4 nadir <300 cells/µl and 29 healthy controls. Supervised and unsupervised analyses were used to identify biomarkers explaining variance between groups defined by HIV status or drug abuse. Relationships between biomarkers and disease markers were examined by Spearman correlation.

Results

The majority (91%) of HIV subjects were on cART, with 38% having undetectable viral loads (VL). Hierarchical clustering identified a biomarker cluster in plasma consisting of two interferon-stimulated gene products (CXCL9 and CXCL10), T cell activation marker (sIL-2R), and monocyte activation marker (sCD14) that distinguished both viremic and aviremic HIV patients on cART from controls (p<0.0001) and were top-ranked in variables important in projection plots. IL-12 and CCL4 were also elevated in viremic and aviremic patients compared to controls (p<0.05). IL-12 correlated with IFNα, IFNγ, CXCL9, and sIL-2R (p<0.05). CXCL10 correlated positively with plasma VL and percentage of CD16+ monocytes, and inversely with CD4 count (p = 0.001, <0.0001, and 0.04, respectively).

Conclusion

A plasma inflammatory biomarker signature consisting of CXCL9, CXCL10, sIL-2R, and sCD14 may be useful as a surrogate marker to monitor immune activation in both viremic and aviremic HIV patients on cART during disease progression and therapeutic responses.     

Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy

Background

HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death.

Methods

A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000–2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models.

Results

4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm³, baseline CD8+ T-cells <500 cells/mm³, time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death.

Conclusions

In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.     

Virologic,Immunologic and Clinical Responses in Foreign-Born versus US-Born HIV-1 Infected Adults Initiating Antiretroviral Therapy: An Observational Cohort Study

Introduction

Mortality rates within the first year of combination antiretroviral therapy (cART) initiation are several-fold higher in resource-limited countries than in resource-replete settings. However studies in western countries examining virologic, immunologic and clinical responses after cART initiation in indigenous versus non-indigenous populations have shown mixed results. This study aimed to determine whether there is a difference in these outcomes in a United States setting between foreign-born and US-born patients.

Methods

This retrospective observational cohort study of HIV-1 infected adults in one urban clinic in the United States compared virologic suppression, immune recovery and rates of AIDS defining events (ADEs) within the first year of cART using linear mixed effect models, log rank tests and Cox proportional hazard models. Data were analyzed for 94 foreign-born and 1242 US-born patients.

Results

Foreign-born patients were younger (31.7 years versus 38.5 years), more often female (38.3% versus 27.1%), less often injection drug users (3.2% versus 9.5%) or men who have sex with men (19.0% versus 54.5%), and had higher loss to follow-up rates (14.9% versus 6.2%). No significant differences were detected between the groups in suppression of plasma HIV-1 RNA, CD4+ cell recovery or development of ADEs.

Conclusions

During the first year on cART, virologic suppression, immune recovery and development of ADEs were comparable between foreign-born and US-born patients in care in a US clinic. Differential rates of loss to follow-up warrant further investigation in the foreign-born population.     

Density of healthcare providers and patient outcomes: evidence from a nationally representative multi-site HIV treatment program in Uganda

Objective

We examined the association between density of healthcare providers and patient outcomes using a large nationally representative cohort of patients receiving combination antiretroviral therapy (cART) in Uganda.

Design

We obtained data from The AIDS Support Organization (TASO) in Uganda. Patients 18 years of age and older who initiated cART at TASO between 2004 and 2008 contributed to this analysis. The number of healthcare providers per 100 patients, the number of patients lost to follow-up per 100 person years and number of deaths per 100 person years were calculated. Spearman correlation was used to identify associations between patient loss to follow-up and mortality with the healthcare provider-patient ratios.

Results

We found no significant associations between the number of patients lost to follow-up and physicians (p = 0.45), nurses (p = 0.93), clinical officers (p = 0.80), field officers (p = 0.56), and healthcare providers overall (p = 0.83). Similarly, no significant associations were observed between mortality and physicians (p = 0.65), nurses (p = 0.49), clinical officers (p = 0.73), field officers (p = 0.78), and healthcare providers overall (p = 0.73).

Conclusions

Patient outcomes, as measured by loss to follow-up and mortality, were not significantly associated with the number of doctors, nurses, clinical officers, field officers, or healthcare providers overall. This may suggest that that other factors, such as the presence of volunteer patient supporters or broader political or socioeconomic influences, may be more closely associated with outcomes of care among patients on cART in Uganda.