Background
Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Sub-clinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with sub-clinical cryptococcosis and the efficacy of preemptive fluconazole.
Methods
609 ART-naïve adults with AIDS initiating ART in Kampala, Uganda had a serum CRAG prospectively measured during 2004–2006. The number needed to test/treat (NNT) with a positive CRAG was assessed for ≥30-month outcomes.
Results
In the overall cohort, 50 persons (8.2%) were serum CRAG positive when starting ART. Of 295 people with CD4+ ≤ 100cells/μL and without prior CM, 26 (8.8%: 95% CI: 5.8–12.6%) were CRAG positive of whom 21 were promptly treated with fluconazole (200–400mg) for 2–4 weeks. Clinical CM developed in 3 fluconazole-treated persons, and 30-month survival was 71% (95% CI: 48%–89%). In the 5 CRAG positive persons with CD4+≤ 100 cell/μL treated with ART but did not fluconazole, all died within 2 months of ART initiation.
The NNT with CRAG screening and fluconazole to prevent one CM case is 11.3 (95%CI: 7.9–17.1) at costs of $190 (95%CI: $132–$287). The NNT to save one life is 15.9 (95%CI: 11.1–24.0) at costs of $266 (95% CI: $185–$402). The cost per disability-adjusted life year (DALY) saved is $21 (95%CI: $15 to $32).
Conclusions
Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4+≤ 100 cells/μL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.
These data demonstrate the effectiveness of ART in a low-resource setting. Children and patients of all ages taking the d4T/3TC/NVP regimen were more likely to have viral failure. Our data suggest that viral failure occurring 6 months or more after the start of ART regimens commonly used in Uganda is likely to be associated with NNRTI- and 3TC-resistant virus.
We show a significant early mortality in our ART cohort in resource-limited settings that is driven by advanced human immunodeficiency virus disease and characterized by low CD4 cell counts. In our experience, the contribution of IRIS to this observed early mortality is limited.
BackgroundLifelong antiretroviral therapy for HIV infected pregnant and lactating women (Option B+) has been rapidly scaled up but there are concerns about poor retention of women initiating treatment. However, facility-based data could underestimate retention in the absence of measures to account for self-transfers to other facilities. We assessed retention-in-care among women on Option B+ in Uganda, using facility data and follow-up to ascertain transfers to other facilities.MethodsIn a 25-month retrospective cohort analysis of routine program data, women who initiated Option B+ between March 2013 and March 2015 were tracked and interviewed quantitatively and qualitatively (in-depth interviews). Kaplan Meier survival analysis was used to estimate time to loss-to-follow-up (LTFU) while multivariable Cox proportional hazards regression was applied to estimate the adjusted predictors of LTFU, based on facility data. Thematic analysis was done for qualitative data, using MAXQDA 12. Quantitative data were analyzed with STATA® 13.ResultsA total of 518 records were reviewed. The mean (SD) age was 26.4 (5.5) years, 289 women (55.6%) attended primary school, and 53% (276/518) had not disclosed their HIV status to their partners. At 25 months post-ART initiation, 278 (53.7%) were LTFU based on routine facility data, with mean time to LTFU of 15.6 months. Retention was 60.2 per 1000 months of observation (pmo) (95% CI: 55.9–64.3) at 12, and 46.3/1000pmo (95% CI: 42.0–50.5) at 25 months. Overall, 237 (55%) women were successfully tracked and interviewed and 43/118 (36.4%) of those who were classified as LTFU at facility level had self-transferred to another facility. The true 25 months post-ART initiation retention after tracking was 71.3% (169/237). Women < 25 years, aHR = 1.71 (95% CI: 1.28–2.30); those with no education, aHR = 5.55 (95% CI: 3.11–9.92), and those who had not disclosed their status to their partners, aHR = 1.59 (95% CI: 1.16–2.19) were more likely to be LTFU. Facilitators for Option B+ retention based on qualitative findings were adequate counselling, disclosure, and the desire to stay alive and raise HIV-free children. Drug side effects, inadequate counselling, stigma, and unsupportive spouses, were barriers to retention in care.ConclusionsRetention under Option B+ is suboptimal and is under-estimated at health facility level. There is need to institute mechanisms for tracking of women across facilities. Retention could be enhanced through strategies to enhance disclosure to partners, targeting the uneducated, and those < 25 years.
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