Clinicians routinely order laboratory tests to monitor plasma viral load (VL) among HIV-infected patients.¹ Patients with suppressed VL have reduced risk for morbidity and mortality and are less likely to transmit HIV to others.^2–6 Viral suppression is the ultimate clinical biomarker for the health outcome and transmission risk of HIV-infected persons. Increasing the percentage of HIV-diagnosed persons in care who are virally suppressed to at least 90% by 2020 is one of key priorities of the National HIV/AIDS Strategies (NHAS).⁷

The most common measure of viral suppression in clinical and surveillance studies is the most recent VL < 200 copies/mL in the past 12 months.^8–12 This single VL measure, however, does not allow a close examination of VL dynamics over time.^4,13,14 Several studies have begun to evaluate longitudinal VL measures.^4,13–15 Data from six HIV clinics showed that using a single VL measure to estimate the percentage of HIV patients with durable viral suppression (all VLs < 200 copies m/L) overestimated by 16% (relative difference) over a 12-month period.¹³ Longitudinal VL measures capture an individual’s cumulative exposure to viral replication over time, serving as a putative proxy biomarker of inflammation and immune system activation. Viremia copy-years, a measure of cumulative plasma burden, predict mortality risk.⁴ Measurement of cumulative viral burden is also an important indicator of HIV transmission risk.⁴ Using data from six clinics, one study examined the amount of person-time spent above 1,500 copies/mL, a VL level at which HIV transmission risk begins to increase.¹⁵ While these findings are informative, clinical cohorts inherently have a degree of selection bias. In comparison, VL data available from the national HIV surveillance system provides a means for conducting population-level assessments of longitudinal plasma HIV burden and transmission risk potential.

Estimating the percentage of HIV-diagnosed persons with durable viral suppression, and examining cumulative plasma HIV burden and transmission risk potential can provide helpful indicators for monitoring NHAS priorities and guiding prevention and treatment efforts. In this analysis, we used data from the Centers for Disease Control and Prevention’s (CDC’s) National HIV Surveillance System (NHSS) to estimate the percentage of persons in HIV care who achieved durable viral suppression over a 2-year period. We also examined the cumulative plasma HIV burden and transmission risk potential among persons in care. These longitudinal measures were examined by sex, race and ethnicity, HIV transmission category, age, year of diagnosis, and gaps in care to identify subgroups of persons who may need more intensive clinical and behavioral interventions.

A total of 808,203 persons with HIV infection aged ≥13 years were diagnosed in the United States or the District of Columbia before 2011 and alive at the end of 2013. More than half (425,264 persons, 52.6%) resided in the 17 jurisdictions at time of diagnosis. The demographic characteristics were similar among the persons from the 17 jurisdictions compared to all persons living with diagnosed HIV (Table 1). There were fewer black/African American and more Hispanic/Latino persons in the 17 jurisdictions, when compared to the persons from the remaining 34 jurisdictions (39.4% vs. 45.2%; 24.4% vs 15.4%, respectively). These were the only two differences greater than 5%.

Sixty-two percent of the 425,264 persons in the 17 jurisdictions (n = 265,264) had at least one VL in 2011. The analytic cohort consisted of 238,641 persons with diagnosed HIV in care who had at least one VL in 2011 and at least two VLs in the two-year observation period (2012–2013). The median number of VL tests per individual during the 2-year period was five (IQR 3–6). The majority of the analytic cohort were male (76.1%), had infection attributed to male-to-male sexual contact (49.1%), and were aged 35 years and older (82.5%). Black/African American, white, Hispanic/Latino, and other races comprised 37.5%, 31.3%, 24.7% and 6.4%, respectively. Eighty-five percent were diagnosed prior to 2008, and 86.2% did not have gaps in care over the 2-year period (Table 2).

During the 2-year observation period, 82.9% of the analytic cohort had a suppressed VL on their latest test. However, only 61.8% had durable viral suppression during the same 2-year period. Regardless the number of VL test results an individual had, 28,777 persons had a single VL > 200 copies/mL during the 2-year observation period and the median was 907 copies/mL (range: 201 to 10,000,000 copies/mL). In the full analytic cohort, the geometric mean viremia copy-years was 345 and the mean numbers of days a person spent above 200, 1,500, and 10,000 copies/mL were 173, 124, and 84 days, corresponding to 23.7%, 17.0%, and 11.5% of the 2-year observation time. There were several significant group differences. Table 2 shows that the percentages of persons with durable viral suppression were lower among females (vs. males), and persons with gaps in care (vs. not). Compared with whites, significantly fewer Hispanic/Latino, other races, and blacks/African Americans had durable viral suppression over the two years. By transmission categories, the percentage who had durable viral suppression was significantly higher among MSM compared to all the other transmission groups. By age, the percentage of persons with durable viral suppression was lowest in the youngest age group (13–24 years) and the percentages increased with age. The only difference between univariate and multivariate results was observed in the year of diagnosis variable. This variable was affected by the age group in the multivariate model as higher percentages of younger age groups were diagnosed in 2008–2010 compared to older age groups.

Several group differences were also observed for cumulative plasma HIV burden and HIV transmission risk potential in the analyses of the full analytic cohort (Table 3). Women, racial/ethnic groups other than white, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, persons diagnosed in 2008–2010, and persons with a gap in care had significantly higher viremia copy-years and person-time above 200, 1500, and 10,000 copies/mL, compared to their respective counterparts. There were no differences in univariate and multivariate results.

Table 4 reports results for 91,120 persons (38.2% of the analytic cohort) who did not achieve durable viral suppression during the 2-year period, the geometric mean viremia copy-years was 7,261, approximately 21 times higher than the mean observed in the full analytic cohort. As seen in Table 4, the mean number of days spent above 200 copies was 438 days, corresponding to 60% of the 2-year time. The mean numbers of days above 1,500 copies and 10,000 copies/mL were 316 days and 215 days, corresponding to 43.2% and 29.5% of the 2-year time. The patterns in cumulative plasma burden and HIV transmission risk potential among groups were, in general, similar to the patterns observed for the full analytic cohort. Both univariate and multivariate analyses showed that greater viral burden was observed among women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, persons diagnosed in 2008–2010, and persons with gaps in care. Three groups had viremia copy-years above 10,000 copies m/L, including persons aged 13–24, persons aged 25–34 years, and persons with gaps in care. The groups with higher copy-years, in general, also spent greater numbers of days during the 2-year period having VLs above 1,500 and 10,000 copies/mL.

We used national HIV surveillance data to assess, for the first time, three longitudinal measures of VL dynamics on the population level: durable viral suppression, cumulative plasma HIV burden, and transmission risk potential. Approximately 62% of persons in HIV care had durable viral suppression for two years, indicating sustained treatment success. However, 38% of persons in care did not achieve durable viral suppression and the viral levels above 200 copies/mL were not simply blips but averaged 7,261 copies/mL. Those who did not sustain durable viral suppression also spent an average of 60% of the 2-year time with VL above 200 copies/mL as well as a considerable length of time above 1,500 and 10,000 copies/mL, posing risk for further transmission.^5,15 The dynamic VL trajectories are easily overlooked with the cross-sectional assessment of last VL measure, which revealed 82.9% suppression in the analytic cohort. Clearly, these longitudinal measures of VL dynamics provide more granular data with implications for HIV treatment and prevention.

Our analyses have several important implications for clinical practices, disease monitoring, and care and prevention efforts. First, evidence shows that patients who missed clinic appointments (i.e., no-shows without prior cancellation) were less likely to maintain suppressed viral load.¹³ To identify patients at risk of not maintaining viral suppression, clinicians might benefit from a closer examination of a patient’s historical context of clinic attendance, missed visits, and VL patterns (e.g., instability, wide swings) to identify patients who may be at risk of not maintaining suppression, or not achieving durable VL suppression.

Second, brief counseling messages delivered by clinicians during routine HIV care visits have been found to reduce HIV transmission risk behaviors among HIV patients.¹⁶ Findings from the Medical Monitoring Project (MMP) showed that HIV patients who were not virally suppressed were more likely to receive HIV/STD prevention messages from a health care provider than those who were virally suppressed (49% vs. 42%).¹⁷ However, there is still considerable room to increase provider’s delivery of brief prevention messages, especially to those who are not durably suppressed as recommended by the prevention, treatment, and care guidelines.^{2,18, 19} Several integrated interventions that target multiple risk behaviors simultaneously have shown to improve risk reduction behaviors and care outcomes of HIV-infected person.²⁰ Those integrated interventions are additional resources for providers to consider when referring patients to more intensive interventions.

Third, we detected disparities in durable viral suppression, cumulative plasma burden, and transmission risk potential, similar to disparities in HIV infection, care engagement, and treatment outcomes that have been highlighted through HIV surveillance data in the United States.^2,12,21 Factors other than individual attributes related to sex, race and ethnicity, age, and care history may be contributing to these disparities. Social and structural factors such as income, employment, education, housing, health insurance coverage, and access to care have been shown to be associated with disparities in HIV infection²¹ and engagement in HIV-related medical care,^{7, 22} which may have affected viral burden and HIV transmission risk potential.

Fourth, as HIV surveillance laboratory results are being increasingly used to inform initiatives to enhance HIV care engagement,²³ our longitudinal indicators may be helpful for public health planning and guiding resource allocation. Beyond using the most recent VL value to estimate population-level viral suppression in a given jurisdiction when constructing an annual care continuum, the totality of VL measures reported to surveillance can be used to assess durable viral suppression longitudinally, as well as identify persons with particularly high cumulative viral burden and proportion time above VL levels that elevate the risk of HIV transmission for targeted outreach interventions.

Fifth, knowing the degree of cumulative viremia burden and the amount of time an individual patient spent above VL levels that increase the risk of HIV transmission can improve the accuracy of estimates of HIV clinical events and onward transmission. Along with risk behavior data, transmission risk modeling efforts can more accurately estimate how many partners are placed at high risk of infection during a window of time, relative to estimates based upon a single cross-sectional VL value.

Our analyses are subject to the following limitations. First, the analysis cohort consisted of persons who had at least one VL test in 2011 as an indicator of at least one care visit during that time. Persons who had no evidence of being in care in 2011 and not included in our analyses may have had unsuppressed VL and elevated HIV transmission risk during the observation period, unless they moved to another jurisdiction and entered care there. The absence of data on transmission potential from persons without a VL complicates the prediction of HIV transmission in the general population. Second, how the three longitudinal indicators examined here predict actual HIV transmission is beyond the scope of the present study; however, with additional jurisdictions implementing complete laboratory reporting such assessments may be feasible in the future. Third, findings are based on persons who had at least one VL in 2011 reported to NHSS. Having a VL test does not necessarily mean that the person actually received appropriate HIV medical care. Patient-level data on antiretroviral therapy are not available to verify individual treatment status. Fourth, we used data from 17 jurisdictions with complete reporting of VL data. For persons who moved to another jurisdiction outside of the 17 jurisdictions during 2012–2013, records may not be available on VL tests. Fifth, data on income and insurance status are not collected in NHSS for directly examining their relationship with viral burden and transmission risk potential.

In summary, about two-thirds of persons in HIV care had durable viral suppression over a 2-year period. The remaining one-third had high cumulative plasma HIV burden and spent a considerable amount of time with their viral loads at levels that increase the risk for transmitting HIV to others. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression.