Correction of estimates of retention in care among a cohort of HIV-positive patients in Uganda in the period before starting ART: a sampling-based approach.

OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics

Low prevalence of Plasmodium falciparum antigenaemia among asymptomatic HAART-treated adults in an urban cohort in Uganda

<p>Abstract</p> <p>Background</p> <p>Presumptive treatment of malaria is common practice in malaria endemic resource-limited settings. With the changing epidemiology of malaria and the introduction of artemisinin-based combination therapy (ACT), there is increasing need for parasite-based malaria case management to prevent unnecessary use of anti-malarial medicines, improve patient care in parasite-positive patients and identify parasite-negative patients in whom another diagnosis must be sought. Although parasitological confirmation by microscopy or alternatively by malaria rapid diagnostic tests (RDTs) is recommended in all patients suspected of malaria before treatment, gaps remain in the implementation of this policy in resource-limited settings. There is need to evaluate the use of RDTs among highly active anti-retroviral therapy (HAART)-treated people living with HIV (PLHIV).</p> <p>Methods</p> <p>Within an urban prospective observational research cohort of 559 PLHIV initiated on HAART and cotrimoxazole prophylaxis between April, 2004 and April, 2005, 128 patients with sustained HIV-RNA viral load < 400 copies/ml for four years were evaluated, in a cross-sectional study, for asymptomatic malaria infection using a histidine-rich protein-2 (HRP-2) RDT to detect <it>Plasmodium falciparum </it>antigen in peripheral blood. Patients with positive RDT results had microscopy performed to determine the parasite densities and were followed for clinical signs and symptoms during the subsequent six months.</p> <p>Results</p> <p>Of the 128 asymptomatic patients screened, only 5 (4%) had asymptomatic <it>P. falciparum </it>antigenaemia. All the patients with positive HRP2 RDT results showed malaria parasites on thick film with parasite densities ranging from 02-15 malaria parasites per high power field. None of the patients with positive RDT results reported signs and symptoms of malaria infection during the subsequent six months.</p> <p>Conclusions</p> <p>In an urban area of low to moderate stable malaria transmission, there was low HRP2 P. <it>falciparum </it>antigenaemia among PLHIV after long-term HAART and cotrimoxazole prophylaxis. Parasite-based malaria diagnosis (PMD) is recommended among PLHIV that are on long-term anti-retroviral therapy. RDTs should be utilized to expand PMD in similar settings where microscopy is unavailable.</p

Quantifying retention during pre-antiretroviral treatment in a large urban clinic in Uganda.

BACKGROUND: Retention studies are usually focused on patients on antiretroviral treatment (ART), however in Sub-Saharan Africa many patients get lost to program (LTP) in the pre-ART care period.. We investigated the proportion of patients not retained in care and factors associated with LTP (dead or lost to follow up ≥6 months) in the pre-ART care period. METHODS: We analyzed data from the Infectious Diseases Institute, Kampala, Uganda. We included all adult patients ≥18 years, ART naïve at program enrollment from 1(st)/Jan/2005. We described the number of patients not retained in care during the 3 steps of enrollment-to-treatment "cascade": Step 1) From enrollment to CD4 count testing, Step 2) ART eligibility assessment. Patients were initially considered eligible if CD4 count was 500 cell/μL in 2014), this could lead to an increase in program retention as more people fall under the recommended threshold and seek care

Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on Antiretroviral Therapy (ART) in sub-Saharan Africa: Frequency and clinical significance

<p>Abstract</p> <p>Background</p> <p>A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda</p> <p>Methods</p> <p>We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04–04/05. We described the patterns of SO-CD4 both in terms of:- I) magnitude of CD4 cell increase (a CD4 count increase < 50 CD4 cells/μl at 6 months, <100 cells/μl at 12 months; and <200 cells/μl at 24 months of ART) and II) failure to achieve a CD4 cell count above 200 cells/μl at 6,12 and 24 months of ART. Using criteria I) we used logistic regression to determine the predictors of SO-CD4. We compared the cumulative risk of clinical events (death and/or recurrent or new AIDS-defining illnesses) among patients with and without SO-CD4.</p> <p>Results</p> <p>Of 559 patients initiating ART, 386 (69%) were female. Median (IQR) age and baseline CD4 counts were 38 yrs (33–44) and 98 cells/μl (21–163) respectively; 414 (74%) started a d4T-based regimen (D4T+3TC+NVP) and 145 (26%) a ZDV-based regimen (ZDV+3TC+EFV). After 6, 12 and 24 months of ART, 380 (68%), 339 (61%) and 309 (55%) had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%), 151 (45%) and 166 (54%) respectively had SO-CD4 based on criteria I), and 165(43%), 143(42%) and 58(19%) respectively based on criteria II). With both criteria combined, 56 (15%) and 129 (38%) had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58%) of those that had SO-CD4 at 6 months (using criteria I) maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12–29)] and without SO-CD4 [23/100PYO (19–28)].</p> <p>Conclusion</p> <p>Using criteria I), the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T-cell functional recovery among patients with SO-CD4.</p

Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective study.

Setting: Government health centres and hospitals (six urban and 20 rural) providing tuberculosis (TB) treatment for people living with the human immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To identify and quantify modifiable factors that limit TB treatment success among PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine Uganda National Tuberculosis and Leprosy Programme clinic registers and patient files of HIV-positive patients who received anti-tuberculosis treatment in 2014. Results: Of 191 rural patients, 66.7% achieved treatment success compared to 81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P < 0.01, generalised estimating equation model). Loss to follow-up was higher and follow-up sputum smear results were less frequently recorded in TB clinic registers among rural patients. Patients receiving treatment at higher-level facilities in rural settings had greater odds of treatment success, while patients receiving treatment at facilities where drug stock-outs had occurred had lower odds of treatment success. Conclusion: Lower reported treatment success in rural settings is mainly attributed to clinic-centred factors such as treatment monitoring procedures. We recommend strengthening treatment monitoring and delivery

Evaluation of WHO Criteria for Viral Failure in Patients on Antiretroviral Treatment in Resource-Limited Settings

Our objective was to evaluate outcomes in patients with sustained viral suppression compared to those with episodes of viremia. Methods. In a prospective cohort of patients started on ART in Uganda and followed for 48 months, patients were categorized according to viral load (VL): (1) sustained-suppression: (VL ≤1,000 copies/mL) (2) VL 1,001–10,000, or (3) VL >10,000. Results. Fifty-Three (11.2%) and 84 (17.8%) patients had a first episode of intermediate and high viremia, respectively. Patients with sustained suppression had better CD4+ T cell count increases over time compared to viremic patients (P < .001). The majority of patients with viremia achieved viral suppression when the measurement was repeated. Only 39.6% of patients with intermediate and 19.1% with high viremia eventually needed to be switched to second line (P = .008). Conclusions. The use of at least one repeat measurement rather than a single VL measurement could avert from 60% to 80% of unnecessary switches

Describing Point of Entry into Care and Being Lost to Program in a Cohort of HIV Positive Pregnant Women in a Large Urban Centre in Uganda.

Introduction. We aim to describe the time of entry into care and factors associated with being lost to program (LTP) in pregnant women on Option B Plus in an integrated HIV and antenatal care (ANC) clinic in Uganda. Methods. We included all pregnant women enrolled into the integrated HIV-ANC clinic from January 2012 to 31st July 2014, while the follow up period extended up to October 30th 2015. LTP was defined as being out of care for ≥3 months. Results. Overall 856 women were included. Only 36.4% (86/236) of the women were enrolled in the first trimester. Overall 69 (8.1%) were LTP. In the multivariate analysis older women (HR: 0.80 per five-year increase, CI: 0.64–1.0, and P=0.060) and women on ART at the time of pregnancy (0.58, CI: 0.34–0.98, and P=0.040) were more likely not to be LTP. Among women already on ART at the time of pregnancy no factor was associated with LTP. Conclusion. Our results suggest the need for interventions to enhance prompt linkage of HIV positive women to HIV services for ART initiation and for increased retention particularly in young and ART naive women

CD4 trajectory adjusting for dropout among HIV-positive patients receiving combination antiretroviral therapy in an East African HIV care centre

Objective: Estimates of CD4 response to antiretroviral therapy (ART) obtained by averaging data from patients in care, overestimate population CD4 response and treatment program effectiveness because they do not consider data from patients who are deceased or not in care. We use mathematical methods to assess and adjust for this bias based on patient characteristics. Design: We examined data from 25,261 HIV-positive patients from the East Africa IeDEA Consortium. Methods: We used inverse probability of censoring weighting (IPCW) to represent patients not in care by patients in care with similar characteristics. We address two questions: What would the median CD4 be “had everyone starting ART remained on observation?” and “were everyone starting ART maintained on treatment?” Results: Routine CD4 count estimates were higher than adjusted estimates even under the best-case scenario of maintaining all patients on treatment. Two years after starting ART, differences between estimates diverged from 30 cells/µL, assuming similar mortality and treatment access among dropouts as patients in care, to over 100 cells/µL assuming 20% lower survival and 50% lower treatment access among dropouts. When considering only patients in care, the proportion of patients with CD4 above 350 cells/µL was 50% adjusted to below 30% when accounting for patients not in care. One-year mortality diverged 6–14% from the naïve estimates depending on assumptions about access to care among lost patients. Conclusions: Ignoring mortality and loss to care results in over-estimation of ART response for patients starting treatment and exaggerates the efficacy of treatment programs administering it

Comparison of different cardiovascular risk tools used in HIV patient cohorts in sub-Saharan Africa; do we need to include laboratory tests?

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death globally, representing 31% of all global deaths. HIV and long term anti-retroviral therapy (ART) are risk factors for development of CVD in populations of people living with HIV (PLHIV). CVD risk assessment tools are currently being applied to SSA populations, but there are questions about accuracy as well as implementation challenges of these tools in lower resource setting populations. We aimed to assess the level of agreement between the various cardiovascular screening tools (Data collection on Adverse effects of anti-HIV Drugs (D:A:D), Framingham risk score, WHO risk score and The Atherosclerotic Cardiovascular Disease Score) when applied to an HIV ART experienced population in Sub-Saharan Africa. METHODS: This study was undertaken in an Anti-Retroviral Long Term (ALT) Cohort of 1000 PLHIV in care who have been on ART for at least 10 years in urban Uganda. A systematic review was undertaken to find the most frequently used screening tools from SSA PLHIV populations; these were applied to the ALT cohort. Levels of agreement between the resulting scores (those including lipids and non-lipids based, as well as HIV-specific and non-HIV specific) as applied to our cohort were compared. Prevalence Bias Adjusted Kappa was used to evaluate agreement between tools. RESULTS: Overall, PLHIV in ALT cohort had a median score of 1.1-1.4% risk of a CVD event over 5 years and 1.7-2.5% risk of a CVD event over 10 years. There was no statistical difference in the risk scores obtained for this population when comparing the different tools, including comparisons of those with lipids and non-lipids, and HIV specific vs non-HIV specific. CONCLUSION: The various tools yielded similar results, but those not including lipids are more feasible to apply in our setting. Long-term cohorts of PLHIV in SSA should in future provide longitudinal data to evaluate existing CVD risk prediction tools for these populations. Inclusion of HIV and ART history factors to existing scoring systems may improve accuracy without adding the expense and technical difficulty of lipid testing