INTRODUCTION: HIV RNA viral load (VL) has been shown to increase during opportunistic illnesses (OIs), suggesting active HIV replication in response to infection among patients not taking antiretroviral therapy (ART). We assessed the effects of OIs on HIV RNA VL and CD4+ T cell counts among patients on ART with initially suppressed VL. METHODS: Between 2003 and 2007, we enrolled and followed 1094 HIV-1-infected adults who initiated ART and had quarterly blood draws for VL and CD4+ T cell count. In VL/CD4+ T cell measurement intervals following undetectable VL, we compared the elevation in VL to detectable levels and CD4+ T cell count changes between intervals when participants had episodes of OIs and intervals when they did not have OIs. RESULTS: VL was more likely to be detectable if participants had OIs in the prior three months compared to when they did not (OR=4.0 (95% CI=1.9-8.6)). The CD4+ T cell counts declined 24.1 cells/microL per three months in intervals where the participants had OIs compared to an increase of 21.3 cells/microL per three months in intervals where they did not have OIs (adjusted difference in the rate of CD4+ T cell count change of 61.7 cells/microL per three months (95% CI=13.7-109.7), P value=0.012). The rate of CD4+ T cell count increase was 25.6 cells/microL per three months (95% CI=11.6-39.6) higher for females compared to males (p value=<0.001), 1.4 cells/microL per three months lower per one year increase in age (p value=0.046) and 4 cells/microL per three months lower per 10 cells/microL increase in the starting CD4+ T cell count value (p value=<0.001). CONCLUSION: Episodes of opportunistic infections among patients taking ART with undetectable VL were associated with elevation of HIV RNA VL to detectable levels and decline in CD4+ T cell counts. CLINICAL TRIAL NUMBER: NCT00119093.

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 x10(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 ( GBP 12,780, EUR 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.

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 x 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 x 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.

BACKGROUND: Long-term impact of antiretroviral therapy (ART) on sexual HIV-transmission risk in Africa is unknown. We assessed sexual behavior changes and estimated HIV transmission from HIV-infected adults on ART in Uganda. METHODS: Between 2003 and 2007, we enrolled and followed ART-naive HIV-infected adults in a home-based AIDS program with annual counseling and testing for cohabitating partners, participant transmission risk-reduction plans, condom distribution and prevention support for cohabitating discordant couples. We assessed participants' HIV plasma viral load and partner-specific sexual behaviors. We defined risky sex as intercourse with inconsistent/no condom use with HIV-negative or unknown serostatus partners in previous 3 months. We compared rates using Poisson regression models, estimated transmission risk using established viral load-specific transmission estimates, and documented sero-conversion rates among HIV-discordant couples. RESULTS: Of 928 participants, 755 (81%) had 36 months data: 94 (10%) died and 79 (9%) missing data. Sexual activity increased from 28% (baseline) to 41% [36 months (P < 0.001)]. Of sexually active participants, 22% reported risky sex at baseline, 8% at 6 months (P < 0.001), and 14% at 36 months (P = 0.018). Median viral load among those reporting risky sex was 122 500 [interquartile range (IQR) 45 100-353 000] copies/ml pre-ART at baseline and undetectable at follow-up. One sero-conversion occurred among 62 cohabitating sero-discordant partners (0.5 sero-conversions/100 person-years). At 36 months, consistent condom use was 74% with discordant partners, 55% with unknown and 46% with concordant partners. Estimated HIV transmission risk reduced 91%, from 47.3 to 4.2/1000 person-years. CONCLUSIONS: Despite increased sexual activity among HIV-infected Ugandans over 3 years on ART, risky sex and estimated risk of HIV transmission remained lower than baseline levels. Integrated prevention programs could reduce HIV transmission in Africa.