"test-and-treat" approach to reduce HIV transmission.

HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1-4.2 log(10)) and combination antiretroviral therapy-initiating cohorts (5.1-5.3 log(10)) by about one log(10). The proportion of individuals with high (> or = 50,000 (4.7 log(10)) copies/ml) HIV-1 RNA levels ranged from 24%-28% in the general HIV-positive population cohorts to 65%-83% in combination antiretroviral therapy-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, the authors estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and antiretroviral treatment. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%-50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion and the median duration of high viral load period was 350 (269; 428) days post seroconversion. They found that it would be possible to identify all HIV-infected individuals with viral load > or = 50,000 (4.7 log(10)) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate combination antiretroviral therapy after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%-82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified "test-and-treat" strategy targeting such individuals by repeated HIV testing (followed by initiation of combination antiretroviral therapy) might be a useful public health strategy for mitigating the HIV epidemic in some communities.

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Editors’ note: Viral load studies in sub-type B infection have shown that for most people the initial peak of viral load resolves to a steady-state setpoint in 4 to 6 months, with higher viral setpoint associated with an increased risk of disease progression and onward HIV transmission. Although we do not know what the threshold for HIV transmission is, it is assumed to be between 10,000 and 100,000 copies/ml, with 50,000 copies/ml used in most studies. This study of over 4000 people with sub-type C infection participating in 7 cohort studies in Botswana found that 24-28% of people in the general population studies and 65-83% in the populations staring on antiretroviral therapy had viral loads over 50,000. In the acute infection cohort, the mean and median duration of high viral load was about 12 months, with around 33% of people maintaining high viral loads. Modelling to determine the optimal testing frequency to identify these individuals and offer them immediate treatment revealed that more HIV transmission could be prevented (77%) with 6-monthly viral load testing than with an annual test. Clearly, people in need of life-prolonging treatment should be prioritised for access to therapy. Thereafter, strategies such as offering treatment to people who are not eligible for treatment based on CD4 count but who are most likely to transmit to others could be considered.