"Our hands are tied up": current state of safer conception services suggests the need for an integrated care model.

We conducted in-depth interviews with a variety of health care providers (n = 33) in Uganda to identify current services that could support and act as barriers to the provision of safer conception counseling (SCC). Consistent with their training and expertise, providers of all types reported provision of services for people living with a diagnosis of HIV or AIDS who desire a child. Important barriers, including a lack of service integration, poor communication between stakeholders, and the absence of policy guidelines, were identified. Drawing on these data, we propose a model of integrated care that includes both SCC services and prevention of unplanned pregnancies.

"I may not say we really have a method, it is gambling work": knowledge and acceptability of safer conception methods among providers and HIV clients in Uganda.

In this qualitative study, researchers assessed knowledge, acceptability, and feasibility of safer conception methods (SCM; timed unprotected intercourse [TUI], manual self-insemination, and sperm washing) among various health care providers (n = 33) and 48 HIV clients with recent or current childbearing intentions in Uganda. While several clients and providers had heard of SCM (especially TUI), few fully understood how to use the methods. All provider types expressed a desire to incorporate SCM into their practice; however, this will require training and counseling protocols, sensitization to overcome cultural norms that pose obstacles to these methods, and partner engagement (particularly by men) in safer conception counseling.

Rates of virological failure in patients treated in a home-based versus a facility-based HIV-care model in Jinja, southeast Uganda: a cluster-randomised equivalence trial.

BACKGROUND: Identification of new ways to increase access to antiretroviral therapy in Africa is an urgent priority. We assessed whether home-based HIV care was as effective as was facility-based care. METHODS: We undertook a cluster-randomised equivalence trial in Jinja, Uganda. 44 geographical areas in nine strata, defined according to ratio of urban and rural participants and distance from the clinic, were randomised to home-based or facility-based care by drawing sealed cards from a box. The trial was integrated into normal service delivery. All patients with WHO stage IV or late stage III disease or CD4-cell counts fewer than 200 cells per microL who started antiretroviral therapy between Feb 15, 2005, and Dec 19, 2006, were eligible, apart from those living on islands. Follow-up continued until Jan 31, 2009. The primary endpoint was virological failure, defined as RNA more than 500 copies per mL after 6 months of treatment. The margin of equivalence was 9% (equivalence limits 0.69-1.45). Analyses were by intention to treat and adjusted for baseline CD4-cell count and study stratum. This trial is registered at http://isrctn.org, number ISRCTN 17184129. FINDINGS: 859 patients (22 clusters) were randomly assigned to home and 594 (22 clusters) to facility care. During the first year, 93 (11%) receiving home care and 66 (11%) receiving facility care died, 29 (3%) receiving home and 36 (6%) receiving facility care withdrew, and 8 (1%) receiving home and 9 (2%) receiving facility care were lost to follow-up. 117 of 729 (16%) in home care had virological failure versus 80 of 483 (17%) in facility care: rates per 100 person-years were 8.19 (95% CI 6.84-9.82) for home and 8.67 (6.96-10.79) for facility care (rate ratio [RR] 1.04, 0.78-1.40; equivalence shown). Two patients from each group were immediately lost to follow-up. Mortality rates were similar between groups (0.95 [0.71-1.28]). 97 of 857 (11%) patients in home and 75 of 592 (13%) in facility care were admitted at least once (0.91, 0.64-1.28). INTERPRETATION: This home-based HIV-care strategy is as effective as is a clinic-based strategy, and therefore could enable improved and equitable access to HIV treatment, especially in areas with poor infrastructure and access to clinic care.

Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda.

BACKGROUND: In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4-12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates. METHODS: HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4-6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression. RESULTS: 4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport. CONCLUSION: About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.

Integrating research into routine service delivery in an antiretroviral treatment programme: lessons learnt from a cluster randomized trial comparing strategies of HIV care in Jinja, Uganda.

Trials integrated into normal health service delivery are designed to evaluate the effectiveness of interventions under real-life conditions. However, integrating research into service delivery creates many operational challenges and raises ethical dilemmas. Here we discuss the operational and ethical issues arising from such trials using the example of a cluster randomized trial evaluating two strategies of ART delivery in Jinja, south-east Uganda.

Use of WHO clinical stage for assessing patient eligibility to antiretroviral therapy in a routine health service setting in Jinja, Uganda.

In a routine service delivery setting in Uganda, we assessed the ability of the WHO clinical stage to accurately identify HIV-infected patients in whom antiretroviral therapy should be started. Among 4302 subjects screened for ART, the sensitivity and specificity (95% CI) of WHO stage III, IV against a CD4 count < 200 x 106/l were 52% (50, 54%) and 68% (66, 70%) respectively. Plasma viral load was tested in a subset of 1453 subjects in whom ART was initiated. Among 938 subjects with plasma viral load of 100,000 copies or more, 391 (42%, 95% CI 39, 45%) were at WHO stage I or II. In this setting, a large number of individuals could have been denied access to antiretroviral therapy if eligibility to ART was assessed on the basis of WHO clinical stage. There is an urgent need for greater CD4 count testing and evaluation of the utility of plasma viral load prior to initiation of ART to accompany the roll-out of ART.

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda.

OBJECTIVE: To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda. DESIGN: Prospective cohort study. SETTING: Gulu District, northern Uganda. PARTICIPANTS: 1625 adults (aged over 14 years) receiving combination antiretroviral therapy. PRIMARY OUTCOME: all cause mortality. SECONDARY OUTCOMES: impact of covariates (sex, age, CD4 count at start, adherence, tuberculosis at start, duration of treatment, and internally displaced person status) on mortality. RESULTS: Sixty nine (4.2%) patients died during follow-up. The mortality incidence rate was 3.48 (95% confidence interval 2.66 to 4.31) per 100 person years. Patients started treatment with a median CD4 count of 157 (interquartile range 90-220) cells/mul; most (1009; 63%) had World Health Organization stage 2 defined illness. Sixty two patients had pulmonary tuberculosis at the start of treatment. Of the 1521 patients with adherence data, 118 (7.8%) had adherence of less than 95% and 1403 (92.2%) had adherence of 95% or above. CONCLUSION: Patients receiving combination antiretroviral therapy in conflict affected northern Uganda had a mortality comparable to that of patients in peaceful, low income settings and better adherence than patients in higher income settings. These favourable findings highlight the need to expand access to combination antiretroviral therapy in populations affected by armed conflict.

Clinical and immunological outcomes of a national paediatric cohort receiving combination antiretroviral therapy in Uganda.

OBJECTIVE: We aimed to evaluate clinical and immunological outcomes of paediatric patients receiving combination antiretroviral therapy (cART) enrolled in The AIDS Support Organization (TASO) Uganda national HIV/AIDS programme. DESIGN: Observational study of patients (age <14 years) enrolled in 10 clinics across Uganda for which TASO has data. METHODS: We extracted patient demographic, immunological and clinical outcomes from the TASO databases regarding age, sex, cART regimen, CD4 cell count and WHO stage at initiation, tuberculosis, mortality and adherence. Outcomes were analysed using Pearson's rank-order correlations, Wilcoxon's rank sum tests, Cox proportional hazard model and survivor functions. RESULTS: Of the total 770 HIV children on cART, median age was 9 years (interquartile range, 5-13 years), and median follow-up time was 377 days (interquartile range, 173-624 days). Seven hundred and fifty-one children (97.5%) initiated nonnucleoside reverse transcriptase inhibitor-based regimens. Three hundred and sixty-five children (47.5%) initiated cART with severe immune suppression (CD4 cell percentage <15). Of the 18 (2.3%) children that died, mortality was associated with lower CD4 cell percentage at initiation (B coefficient -0.144, standard error 0.06, P = 0.02). Of the total, 229 (30%) were single or double orphans and more likely to initiate cART at an older age (mean age, 9.25 vs. 8.35 years, P = 0.02) and have a lower CD4 cell count (median, 268 vs. 422 cells/microl, P < or = 0.0001) and CD4 cell percentage (median 12.8 vs. 15.5%, P = 0.02) at initiation. Pulmonary tuberculosis was present in 43 (5.6%) patients at initiation and 21 (2.3%) after cART. Almost all patients (94.9%) demonstrated more than 95% adherence. CONCLUSION: Children on cART in Uganda demonstrate positive clinical outcomes. However, additional support is required to ensure timely cART access among orphans and young children.

A cluster-randomised trial to compare home-based with health facility-based antiretroviral treatment in Uganda: study design and baseline findings.

The scale-up of antiretroviral therapy is progressing rapidly in Africa but with a limited evidence-base. We report the baseline results from a large pragmatic cluster-randomised trial comparing different strategies of ART delivery. The trial is integrated in normal health service delivery. 1453 subjects were recruited into the study. Significantly more women (71%) than men (29%) were recruited. The WHO HIV clinical stage at presentation did not differ significantly between men and women: 58% and 53% respectively were at WHO stage III or IV (p=0.9). Median CD4 counts (IQR) x 106 cells/l were 98 (28, 160) among men and 111 (36, 166) among women. Sixty-four percent of women and 61% men had plasma viral load > or =100,000 copies. Baseline characteristics did not change over time. Considerably fewer men than women presented for treatment. Both men and women presented at an advanced stage with very low median CD4 count and high plasma viral load.