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Background: Daily suppression of herpes simplex virus type 2 (HSV-2) reduces plasma HIV-1 concentrations and modestly delayed HIV-1 disease progression in one clinical trial. We investigated the effect of daily suppressive aciclovir on HIV-1 disease progression in Rakai, Uganda., Methods: We did a single site, parallel, randomised, controlled trial of HIV-1, HSV-2 dually infected adults with CD4 cell counts of 300-400 cells per μL. We excluded individuals who had an AIDS-defining illness or active genital ulcer disease, and those that were taking antiretroviral therapy. Participants were randomly assigned (1:1) with computer-generated random numbers in blocks of four to receive either aciclovir 400 mg orally twice daily or placebo; participants were followed up for 24 months. All study staff and participants were masked to treatment, except for the two statisticians. The primary outcome was CD4 cell count less than 250 cells per μL or initiation of antiretroviral therapy for WHO stage 4 disease. Our intention-to-treat analysis used Cox proportional hazards models, adjusting for baseline log(10) viral load, CD4 cell count, sex, and age to assess the risk of disease progression. We also investigated the effect of suppressive HSV-2 treatment stratified by baseline HIV viral load with a Cox proportional hazards model. This trial is registered with ClinicalTrials.gov, number NCT00405821., Findings: 440 participants were randomly assigned, 220 to each group. 110 participants in the placebo group and 95 participants in the treatment group reached the primary endpoint (adjusted hazard ratio [HR] 0·75, 95% CI 0·58-0·99; p=0·040). 24 participants in the placebo group and 22 in the treatment group were censored, but all contributed data for the final analysis. In a subanalysis stratified by baseline HIV viral load, participants with a baseline viral load of 50,000 copies mL or more in the treatment group had a reduced HIV disease progression compared with those in the placebo group (0·62, 0·43-0·96; p=0·03). No significant difference in HIV disease progression existed between participants in the treatment group and those in the placebo group who had baseline HIV viral loads of less than 50,000 copies per mL (0·90, 0·54-1·5; p=0·688). No safety issues related to aciclovir treatment were identified., Interpretation: Aciclovir reduces the rate of disease progression, with the greatest effect in individuals with a high baseline viral load. Suppressive aciclovir might be warranted for individuals dually infected with HSV-2 and HIV-1 with viral loads of 50,000 copies per mL or more before initiation of antiretroviral treatment., Funding: National Institute of Allergy and Infectious Diseases, National Cancer Institute (National Institutes of Health, USA)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In many resource-poor countries, CD4 count thresholds of eligibility for antiretroviral treatment (ART) were initially low (<200 cells/mm3) but are now being increased to improve patient survival and to reduce HIV transmission. There are few quantitative data on the effect of such increases on the demand for ART. The objective of this study was to measure HIV prevalence and the proportion of HIV-positives eligible for antiretroviral therapy at different CD4 cut-off levels among users of public health care services in Kampala, Uganda. We recruited 1200 adults from three primary care clinics in Kampala, including equal numbers of family planning (FP) clients, pregnant women, adult patients with any complaint, and persons seeking HIV counseling and testing. All participants were screened for HIV and those positive had a CD4 count done. HIV prevalence in all patients was 16.9% (203/1200). ART eligibility based on CD4 counts significantly increased from 36% at a 200 cells/mm3 cut-off to 44% at 250 cells and to 57% at 350 cells cut-off (p for χ2 trend<0.001). We concluded that changing cut-off levels to higher CD4 counts will significantly increase patient load in Kampala's primary care clinics, but a phased implementation should minimize negative effects on quality of care. [ABSTRACT FROM AUTHOR]