HIV-infected ugandan adults taking antiretroviral therapy with CD4 counts >200 cells/µL who discontinue cotrimoxazole prophylaxis have increased risk of malaria and diarrhea.

BACKGROUND: Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/µL. However, this practice has not been evaluated in sub-Saharan Africa. METHODS: Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/µL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/µL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea. RESULTS: At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/µL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001). CONCLUSIONS: HIV-infected adults on ART with CD4 counts >200 cells/µL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.

CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study.

OBJECTIVE: To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART). DESIGN: Cost effectiveness study. SETTING: A randomised trial in a home based ART programme in Tororo, Uganda. PARTICIPANTS: People with HIV who were members of the AIDS Support Organisation and had CD4 cell counts <250 × 10(6) cells/L or World Health Organization stage 3 or 4 disease. MAIN OUTCOME MEASURES: Outcomes calculated for the study period and projected 15 years into the future included costs, disability adjusted life years (DALYs), and incremental cost effectiveness ratios (ICER; $ per DALY averted). Cost inputs were based on the trial and other sources. Clinical inputs derived from the trial; in the base case, we assumed that point estimates reflected true differences even if non-significant. We conducted univariate and multivariate sensitivity analyses. INTERVENTIONS: Three monitoring strategies: clinical monitoring with quarterly CD4 cell counts and viral load measurement (clinical/CD4/viral load); clinical monitoring and quarterly CD4 counts (clinical/CD4); and clinical monitoring alone. RESULTS: With the intention to treat (ITT) results per 100 individuals starting ART, we found that clinical/CD4 monitoring compared with clinical monitoring alone increases costs by $20,458 (£12,780, €14,707) and averts 117.3 DALYs (ICER = $174 per DALY). Clinical/CD4/viral load monitoring compared with clinical/CD4 monitoring adds $142,458, and averts 27.5 DALYs ($5181 per DALY). The superior ICER for clinical/CD4 monitoring is robust to uncertainties in input values, and that strategy is dominant (less expensive and more effective) compared with clinical/CD4/viral load monitoring in one quarter of simulations. If clinical inputs are based on the as treated analysis starting at 90 days (after laboratory monitoring was initiated), then clinical/CD4/viral load monitoring is dominated by other strategies. CONCLUSIONS: Based on this trial, compared with clinical monitoring alone, monitoring of routine CD4 cell count is considerably more cost effective than additionally including routine viral load testing in the monitoring strategy and is more cost effective than ART.

Determinants of early and late mortality among HIV-infected individuals receiving home-based antiretroviral therapy in rural Uganda.

BACKGROUND: Up to 20% of people initiating antiretroviral therapy (ART) in sub-Saharan Africa die during the first year of treatment. Understanding the clinical conditions associated with mortality could potentially lead to effective interventions to prevent these deaths. METHODS: We examined data from participants aged ≥18 years in the Home-Based AIDS Care project in Tororo, Uganda, to describe mortality over time and to determine clinical conditions associated with death. Survival analysis was used to examine variables associated with mortality at baseline and during follow-up. RESULTS: A total of 112 (9.4%) deaths occurred in 1132 subjects (73% women) during a median of 3.0 years of ART. Mortality was 15.9 per 100 person-years during the first 3 months and declined to 0.3 per 100 person-years beyond 24 months after ART initiation. Tuberculosis (TB) was the most common condition associated with death (21% of deaths), followed by Candida disease (15%). In 43% of deaths, no specific clinical diagnosis was identified. Deaths within 3 months after ART initiation were associated with World Health Organization clinical stage III or IV at baseline, diagnosis of TB at baseline, a diagnosis of a non-TB opportunistic infection in follow-up and a body mass index ≤17 kg/m² during follow-up. Mortality after 3 months of ART was associated with CD4 cell counts <200 cells per microliter, a diagnosis of TB or other opportunistic infection, adherence to therapy <95%, and low hemoglobin levels during follow-up. CONCLUSION: Potentially remediable conditions and preventable infections were associated with mortality while receiving ART in Uganda.

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial.

OBJECTIVE: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. DESIGN: Randomised clinical trial SETTING: A home based ART programme in rural Uganda. PARTICIPANTS: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 10(6)/L or World Health Organization stage 3 or 4 disease. INTERVENTIONS: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). MAIN OUTCOME MEASURES: Serious morbidity (newly diagnosed AIDS defining illness) and mortality. RESULTS: 1094 participants started ART; median CD4 count at baseline was 129 cells × 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31). CONCLUSION: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.