Changes in Population HIV RNA Levels in Mbarara, Uganda, During Scale-up of HIV Antiretroviral Therapy Access

In a rural Ugandan community scaling up antiretroviral therapy (ART), we sought to determine if population based HIV RNA levels (population viral load) decreased from 2011-2012

Biomarker-Measured Unhealthy Alcohol Use in Relation to CD4 Count Among Individuals Starting ART in Sub-Saharan Africa.

Individuals are initiating antiretroviral therapy (ART) at earlier HIV disease stages. Unhealthy alcohol use is a known barrier to successful HIV treatment outcomes, yet it is unclear whether the problem varies by disease stage. We measured alcohol use with an objective biomarker (phosphatidylethanol [PEth]), comparing individuals (n = 401) with early (CD4 > 350 cells/mL, WHO Stage 1) versus late (CD4 < 200 cells/mL) ART initiation in HIV care in Uganda and South Africa (SA). We examined the association between CD4 count and biomarker results using multivariable regression modeling, and compared PEth results to self-report to assess underreporting. Overall, 32.2% (n = 129) had unhealthy alcohol use (PEth ≥ 50 ng/ml). Early ART initiation was significantly associated with unhealthy alcohol use in Uganda (AOR 2.65; 95% CI: 1.05-6.72), but not SA (AOR 1.00; 95% CI: 0.46-2.17). In Uganda, 23.2% underreported unhealthy alcohol use versus 11.6% in SA (χ2 = 9.30; p < 0.01). Addressing unhealthy alcohol use is important as patients initiate ART earlier, yet challenging due to underreporting

Timing of Antiretroviral Therapy and Systemic Inflammation in Sub-Saharan Africa: Results From the META Longitudinal Cohort Study

Chronic inflammation predicts complications in persons with human immunodeficiency virus infection. We compared D-dimer, soluble CD14, and interleukin 6 levels before and 12 months after antiretroviral therapy (ART) initiation, among individuals starting ART during earlier-stage (CD4 T-cell count \u3e350/μL) or late-stage disease (CD4 T-cell count \u3c200/ μL). Female sex, older age, viral load, and late-stage disease were associated with pre-ART biomarkers (n = 661; P \u3c .05). However, there were no differences in biomarkers by disease stage after 12 months of ART (n = 438; P \u3e .05), owing to loss from observation and greater declines in biomarkers in latestage initiators (P \u3c .001). Earlier initiation of ART is associated with decreased inflammation, but levels seem to converge between earlier and later initiators surviving to 12 months

Adherence to HIV Antiretroviral Therapy Among Pregnant and Postpartum Women During the Option B+ Era: 12-month Cohort Study in Urban South Africa and Rural Uganda

Introduction: We conducted a cohort study to understand patterns of anti-retroviral therapy (ART) adherence during pregnancy, postpartum and non-pregnancy follow-up among women initiating ART in public clinics offering Option B+ in rural Uganda and urban South Africa. Methods: We collected survey data, continuously monitored ART adherence (Wisepill), HIV-RNA and pregnancy tests at zero, six and twelve months from women initiating ART in Uganda and South Africa, 2015 to 2017. The primary predictor of interest was follow-up time categorized as pregnant (pregnancy diagnosis to pregnancy end), postpartum (pregnancy end to study exit) or non-pregnancy-related (neither pregnant nor postpartum). Fractional regression models included demographics and socio-behavioural factors informed by the Behavioral Model for Vulnerable Populations. We evaluated HIV-RNA at 12 months by ever- versus never-pregnant status. Results: In Uganda, 247 women contributed 676, 900 and 1274 months of pregnancy, postpartum and non-pregnancy-related follow-up. Median ART adherence was consistently ≥ 90%: pregnancy, 94% (interquartile range [IQR] 78,98); postpartum, 90% (IQR 70,97) and non-pregnancy, 90% (IQR 80,98). Poorer adherence was associated with younger age (0.98% [95% CI 0.33%, 1.62%] average increase per year of age) and higher CD4 cell count (1.01% [0.08%, 1.94%] average decrease per 50 cells/ mm3). HIV-RNA was suppressed among 91% (N = 135) ever-pregnant and 86% (N = 85) never-pregnant women. In South Africa, 190 women contributed 259, 624 and 1247 months of pregnancy, postpartum and non-pregnancy-related follow-up. Median adherence was low during pregnancy, 74% (IQR 31,96); postpartum, 40% (IQR 4,65) and non-pregnancy, 77% (IQR 47,92). Poorer adherence was associated with postpartum status (22.3% [95% CI 8.6%, 35.4%] average decrease compared to non-pregnancy-related follow-up) and less emotional support (1.4% [0.22%, 2.58%] average increase per unit increase). HIVRNA was suppressed among 57% (N = 47) ever-pregnant and 86% (N = 93) never-pregnant women. Conclusions: Women in rural Uganda maintained high adherence with 91% of ever-pregnant and 86% of never-pregnant women suppressing HIV-RNA at 12 months. Women in urban South Africa struggled with adherence, particularly during postpartum follow-up with median adherence of 40% and 57% of women with HIV-RNA suppression at one year, suggesting a crisis for postpartum women with HIV in South Africa. Findings suggest that effective interventions should promote emotional support

Acceptability of routine HIV counselling and testing, and HIV seroprevalence in Ugandan hospitals

OBJECTIVE: Mulago and Mbarara hospitals are large tertiary hospitals in Uganda with a high HIV/AIDS burden. Until recently, HIV testing was available only upon request and payment. From November 2004, routine free HIV testing and counselling has been offered to improve testing coverage and the clinical management of patients. All patients in participating units who had not previously tested HIV-positive were offered HIV testing. Family members of patients seen at the hospitals were also offered testing. METHODS: Data collected at the 25 participating wards and clinics between 1 November 2004 and 28 February 2006 were analysed to determine the uptake rate of testing and the HIV seroprevalence among patients and their family members. FINDINGS: Of the 51 642 patients offered HIV testing, 50 649 (98%) accepted. In those who had not previously tested HIV-positive, the overall HIV prevalence was 25%, with 81% being tested for the first time. The highest prevalence was found in medical inpatients (35%) and the lowest, in surgical inpatients (12%). The prevalence of HIV was 28% in the 39 037 patients who had never been tested before and 9% in those who had previously tested negative. Of the 10 439 family members offered testing, 9720 (93%) accepted. The prevalence in family members was 20%. Among 1213 couples tested, 224 (19%) had a discordant HIV status. CONCLUSION: In two large Ugandan hospitals, routine HIV testing and counselling was highly acceptable and identified many previously undiagnosed HIV infections and HIV-discordant partnerships among patients and their family members

Client and Provider Perspectives of the Efficiency and Quality of Care in the Context of Rapid Scale-Up of Antiretroviral Therapy

Global scale-up of antiretroviral therapy (ART) has focused on clinical outcomes with little attention on its impact on existing health systems. In June–August 2008, we conducted a formative evaluation on ART scale-up and clinic operations at three clinics in Uganda to generate lessons for informing policy and larger public health care systems. Site visits and semistructured interviews with 10 ART clients and 6 providers at each clinic were used to examine efficiency of clinic operations (patient flow, staff allocation to appropriate duties, scheduling of clinic visits, record management) and quality of care (attending to both client and provider needs, and providing support for treatment adherence and retention). Clients reported long waiting times but otherwise general satisfaction with the quality of care. Providers reported good patient adherence and retention, and support mechanisms for clients. Like clients, providers mentioned long waiting times and high workload as major challenges to clinic expansion. Providers called for more human resources and stress-release mechanisms to prevent staff burnout. Both providers and clients perceive these clinics to be delivering good quality care, despite the recognition of congested clinics and long waiting times. These findings highlight the need to address clinic efficiency as well as support for providers in the context of rapid scale-up

Closing the gap: A novel metric of change in performance.

BackgroundInterventions to improve performance of global programs in the HIV cascade of care are widespread and increasing the focus of implementation science. At present, however, there is no clear consensus on how to conceptualize their improvement at the program level. The commonly used measures of association, based on ratios of probabilities (or odds), have well-known defects in public health applications. They yield large effect sizes even when the absolute effects, and therefore the public health impact, are small. On the other hand, risk differences create problems because settings with higher baseline values are penalized. We aim to examine ways of quantifying improvement in each health center of a cluster-randomized trial in Uganda to accelerate antiretroviral therapy initiation among HIV-infected adults.MethodsWe formalize the concept of the 'improvement index,' defined as the fraction of gaps closed as a metric of improvement, and suggest that it has unique features and strengths when compared to risk ratios and risk differences.ResultsOverall agreement between the different indices was not high, especially among health centers that were among the top 5 or 10. However, all ranking showed broad similarities at the far ends of the spectrum. On scatter plots, there was a positive linear relationship between the metrics, and the Bland Altman (B-A) plots were in agreement.ConclusionThe improvement index can be used as an alternative measure of association in implementation science interventions. It can be useful for public health purposes as it demonstrates how much can be covered from the baseline

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda.

Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up.Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing.Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of$529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by$100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel,$106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals.In a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions