we developed an ordinary differential equation simulation model for hiv testing and treatment among msm in san francisco extending previous models [ 1 , 4 , 5 ] .
we tested 3 art expansion strategies : ( 1 ) treatment of all individuals currently receiving hiv care with cd4 cell counts < 500 cells / mm ; ( 2 ) treatment of all individuals receiving care ; and ( 3 ) intensified annual hiv testing combined with treatment of all hiv - infected persons ( the full test - and - treat strategy ) .
inputs to the model were based on comprehensive surveillance information on prevalence and incidence of hiv infection , testing rates , and treatment outcomes data available for san francisco from the local health department and electronic patient databases of the san francisco general hospital outpatient hiv treatment clinics that contain information on 95% of individuals known to be hiv infected in san francisco .
we stratified the population of msm according to risk groups , hiv status , cd4 cell count group , and treatment , as follows .
infected men , in turn , are classified according to the untreated nadir cd4 cell count into 1 of 4 stages : cd4 cell count > 500 cells / mm , cd4 cell count of 350500 cells / mm , cd4 cell count of 200350 cells / mm , and cd4 cell count < 200 cells / mm .
individuals in the model may ( 1 ) have unknown serostatus and not be receiving treatment ; ( 2 ) have known hiv infection but not receiving art ; ( 3 ) be receiving art but not yet achieved suppression ; or ( 4 ) be receiving long - term antiretroviral therapy .
eighty percent of individuals receiving long - term therapy were assumed to have achieved durable virological suppression .
untreated individuals progress forward through successive hiv stages according to rates estimated from previous studies .
individuals who have achieved virologic suppression proceed through nadir cd4 cell count stages at a slower rate ( zero in the baseline scenario ) .
individuals in either the short - term incomplete suppression classes have ongoing hiv progression through stages at a rate intermediate between the untreated and completely suppressed groups .
the mean time between initiation of therapy and achievement of full suppression was 3 months .
individuals with complete or incomplete suppression may stop therapy at rates estimated from observed fractions of therapy ( mean of 1% per year ) .
the rate of starting therapy ( or restarting therapy ) depends on the hiv stage .
individuals with a cd4 cell count < 200 are assumed to start therapy with a mean waiting time of 3 months .
the time to initiation of therapy for individuals in other stages is assumed to be 3 months when a test - and - treat program has been initiated and is longer otherwise .
the rate of stopping therapy was higher for individuals with incomplete suppression than for individuals with complete virological suppression .
finally , individuals undergo hiv testing at a rate of 1 test per 3 years in the absence of a treatment program ( and , thus , transition from unknown status to known status ) at this rate .
we assumed 2 risk groups ( high and low ) distinguished by more unprotected contacts per unit time .
eighty percent of the population was assumed to be in the low - risk group .
the transmission probability was assumed to be lower if the infected person was receiving treatment ; we assumed 20% relative transmission for infected persons with incomplete virological suppression and 1% for persons with complete virological suppression .
we assumed nonrandom mixing between the high- and low - risk groups , with a mixing parameter of 0.6 ( 0 for completely random mixing to 1 for completely positive assortative [ like only with like ] mixing ) .
the number of contacts per unit time and the mixing parameter were chosen to give a prevalence of 0.24 in 2007 , in agreement with data . finally , the total population at risk was assumed to be 67,000 and the mean sexually active residence time to be 30 years .
we performed sensitivity analyses on key variable inputs to assess model results variability by repeating model runs with inflated and deflated inputs for single variables chosen from the range of likely values as estimated from the literature and clinic databases .
change in model results were evaluated by calculating percent change in reduction in new hiv infections .
all 3 expanded art strategies resulted in reduction of predicted prevalence of hiv infection and new hiv infections , compared with the 20082009 standard of care of starting art for hiv - infected persons with cd4 cell counts < 350 cells / mm ( see table 1 ) .
significant reductions in new hiv infections were predicted in as early as 5 years from the implementation of expanded art for all 3 strategies .
the test - and - treat all strategy had the largest effect of the 3 expanded art strategies , eventually doubling the number of new hiv infections averted , compared with the least ambitious strategy .
however , significant gains in averting new hiv infections were seen for both of the expanded art strategies ( < 500 and treat all ) that involved changing art initiation practices without implementing additional hiv testing and linkage to care programs .
the model does not predict elimination of the hiv epidemic among msm in san francisco ( reduction of prevalence and incidence of hiv infection to negligible or zero levels ) .
however , at 20 years , the test - and - treat strategy predicts reduction in prevalence of hiv infection among msm in san francisco from 26.2% to 12.8% , greater than reducing the prevalence of hiv infection by half in the absence of changes in 20082009 art practices .
hiv infections averted and percent reduction in new infections are relative to 2009 model estimates .
the model was most sensitive to assumptions of the effectiveness of art in reducing hiv transmission probabilities .
a reduction in the effectiveness of art in reducing hiv transmission from 99% to 90% resulted in a > 30% reduction in the percentage of new hiv infections averted over 20 years .
the model was less sensitive to changes in the proportion of individuals who are able to achieve virological suppression , with a 10% decrease in the proportion achieving suppression resulting in a < 10% decrease in the percentage of new infections averted .
other model input parameters evaluated in sensitivity analyses ( treatment cessation rates , mortality rates , infectiousness with incomplete viral suppression , testing rates , and the proportion in the high - risk group ) demonstrated similar relative effects between the strategies over the range of likely values .
san francisco is one of the original epicenters of the hiv epidemic and remains the site of one of the largest concentrated epidemics of hiv infection in the united states , with a 24% prevalence among msm , exceeding levels reported in other concentrated epidemics , such as msm in new york city and african - american men in washington , dc . despite advancements in treatment and expanded outreach efforts , 600 incident hiv infections occurred in san francisco in 2008 .
new strategies of combination prevention that include both behavioral and biomedical interventions are thus needed .
our model demonstrates that expansion of art to those already in care with cd4 cell counts < 500 cells / mmor at any cd4 cell count is likely to significantly reduce the number of future hiv infections .
further reductions could be gained by the addition of routine annual testing and linkage to care .
these findings extend other models of san francisco and vancouver by anchoring the analysis to empirical data regarding engagement in care and the new department of health & human services ( dhhs ) guidelines for art initiation .
it is instructive to contrast our findings to those of a recent modeling analysis of the hiv epidemic in washington , dc .
our model predicts greater reductions in new hiv infections , compared with analysis from washington , dc .
although the deterministic model with its inherent limitations differed from the stochastic simulation model used by walensky et al may have contributed to these differences ,
the critical difference is that only 50% of persons in the dc model are linked to care after a positive hiv test result .
indeed , these authors and other modeling reports from south africa emphasize the importance of linkage to care as a limiting factor in art expansion strategies reducing incident hiv infections .
when the dc model includes nearly complete linkage to care , results of the models converge .
testing and linkage to care are appropriately one of the highest public health priorities in populations with high prevalence worldwide . in san francisco , with the high rates of hiv testing and linkage to care , we have the opportunity to reduce hiv transmission by expanding art to those already receiving care while we determine the most cost - effective approaches to further expand testing . of importance ,
realization of the prevention benefits of expanded art strategies depend on a number of components .
retention in care and expanded financial , clinical , social , and structural adherence and support measures for treatment , including specific support for psychiatric and substance use comorbid conditions , and addressing homelessness and marginal housing all need to be components of the strategy in a city such as san francisco . also of concern
is the potential for changes in behavior among msm leading to increased transmission risk , thereby offsetting any potential gains and the specter of drug - resistant strains of hiv .
however , these obstacles are not insurmountable , as evidenced by the recent public health commitment and movement to universal art and a comprehensive , multi - level hiv prevention strategy in san francisco .
it is possible that such strategies are comparatively cost - effective and should be evaluated as data become available . of note
, there is little observed evidence of significant increases in hiv transmission risk behavior , and contrary to recent modeling exercises , transmitted drug resistant hiv strains have remained stable or even decreased in san francisco and in similar cities , such as vancouver , where art has rapidly expanded [ 1719 ] .
modeling of complex phenomena , such as a local hiv epidemic and making cogent predictions about the future , are subject to numerous limitations .
in essence , modeling is a thought experiment , informed by data , but subject to the validity and completeness of the model 's internal structures .
the model presented here while able to recapitulate the observed hiv epidemic in san francisco from its beginning with high fidelity does not specifically model the impact of acutely hiv - infected persons , which may be a significant driver of new hiv infections or account for perturbations arising from hiv drug resistance which may affect virological suppression rates ; however , the sensitivity analyses performed indirectly address these issues by varying the reach of hiv testing and art effectiveness in producing viral suppression . in conclusion ,
our projections suggest that ensuring hiv - infected patients in san francisco already receiving care are offered art would significantly reduce the incidence of hiv infection in san francisco .
these predictions are supported by recent surveillance data from san francisco and vancouver that show decreasing rates of new hiv infections that correlate with art expansion and lower community viral load [ 20 , 21 ] . with new national and san francisco health department art guidelines supporting treatment for most hiv - infected persons for their individual health , secondary benefits of reducing hiv transmission
 modeling of expanding antiretroviral treatment to all hiv infected adults already in care in san francisco predicts reductions in new hiv infections at 5 years of 59% among men who have sex with men ( msm ) . 
 addition of annual hiv testing for msm to universal treatment decreases new infections by 76% . 
METHODS
RESULTS
DISCUSSION