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Durable Viral Suppression and Transmission Risk Potential Among Persons With Diagnosed HIV Infection: United States, 2012–2013

  1. H. Irene Hall1
  1. 1Division of HIV/AIDS Prevention, US Centers for Disease Control and Prevention
  2. 2ICF International, Atlanta, Georgia
  3. 3Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham
  1. Correspondence: N. Crepaz, Division of HIV/AIDS Prevention, The U.S. Centers for Disease Control and Prevention, 1600 Clifton Rd, Mailstop E-47, Atlanta, GA 30329 (ncrepaz{at}cdc.gov).

Abstract

Background. We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV)–diagnosed persons in care.

Methods. Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results <200 copies/mL) and examined viremia copy-years and time spent above VL levels that increase the risk of HIV transmission during 2012–2013.

Results. Of 265 264 persons in HIV care in 2011, 238 641 had at least 2 VLs in 2012–2013. The median number of VLs per individual during the 2-year period was 5. Approximately 62% had durable viral suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential.

Conclusions. Two-thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression.

Key words

Clinicians routinely order laboratory tests to monitor plasma viral load (VL) among human immunodeficiency virus (HIV)–infected patients [1]. Patients with suppressed VL have reduced risk for morbidity and mortality and are less likely to transmit HIV to others [26]. 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 a key priority of the National HIV/AIDS Strategy (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 [812]. This single VL measure, however, does not allow for a close examination of VL dynamics over time [4, 13, 14]. Several researchers have begun to evaluate longitudinal VL measures [4, 1315]. Data from 6 HIV clinics showed that use of 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 6 clinics, one study examined the amount of person-time spent above 1500 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 (NHSS) provide a means for conducting population-level assessments of longitudinal plasma HIV burden and transmission risk potential.

Estimation of 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) 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.

METHODS

Analysis Cohort

HIV infection is reportable in all 50 states, the District of Columbia, and 6 US dependent areas. However, not all areas have mandatory reporting of all HIV-related laboratory tests, including all values of CD4 cell counts (or percentages) and VL tests. We used the NHSS data reported to CDC through July 2015 from 17 jurisdictions (California, the District of Columbia, Hawaii, Illinois, Indiana, Iowa, Louisiana, Maryland, Michigan, Missouri, New Hampshire, New York, North Dakota, South Carolina, Texas, Utah, and West Virginia) with complete reporting of CD4 cell count and VL test results to NHSS for 2011–2013.

The analytic cohort included persons who were aged ≥13 years with HIV infection diagnosed before 2011, who resided in the 17 jurisdictions at time of diagnosis, were alive at the end of 2013, and had at least 1 VL test in 2011 (an indicator of at least 1 care visit) and at least 2 VL results during the 2-year observation period (2012–2013).

Durable Viral Suppression

To be consistent with the most recent surveillance and care continuum studies as well as the NHAS indicator definition, a cutpoint of <200 copies/mL was used to define viral suppression. Durable viral suppression was defined as all VL values <200 copies/mL over the 2-year period. We determined the viral suppression status for each patient and calculated the percentage who had durable viral suppression.

Viremia Copy-Years

Viremia copy-years were calculated to determine cumulative plasma HIV burden [4]. The 2-year observation period was first divided into smaller time intervals defined by pairs of consecutive VL tests. HIV plasma burden for each time interval between 2 consecutive VL values was calculated by multiplying the average of the 2 VL values by the time interval between the 2 VL measures. The viremia copy for each segment of a person's VL curve was then summed to calculate viremia copy-years for the 2-year period (2012–2013). For persons who did not have a VL at the beginning of the 2-year period (on 1 January 2012) or at the end of the 2-year period (on 31 December 2013), the last VL test result in 2011 and the first VL test in 2014 were used to proportionally interpolate the VL values on those dates when the VL tests were available. Otherwise, the first VL test result and the last VL test result in the 2-year period were used on those dates. The distribution of the viremia copy-years was highly skewed, with a few having had extreme values. To normalize the ranges of viremia copy-years, we used the geometric mean instead of the arithmetic mean.

Person-Time Above Selected Viral Load Levels

Using the method developed by Marks et al [15], we estimated the amount of time (in days) spent above 1500 copies/mL for each pair of VL results, summed the estimated number of days above the 1500 cutpoint to yield a single value per person, and then aggregated the amount of person-time above the cutpoint across the analytic cohort over the 2-year period. Given evidence suggesting a dose-response relationship between increasing plasma viremia and sexual transmission in serodiscordant couples [5], we also used a higher plasma level (10 000 copies/mL) to examine HIV transmission risk potential. In addition, we used the same method to calculate the amount of time a person spent above 200 copies/mL to better understand the length of time not maintaining viral suppression over a 2-year period. For persons who did not have a VL test at the beginning of the 2-year period (on 1 January 2012) or at the end of the 2-year period (on 31 December 2013), a similar linear proportional interpolation method to that described above for calculating viremia copy-years was used for calculating person-time above a cutpoint.

Statistical Analyses

We assessed the 3 VL measures by the following stratification variables: sex (male, female), race and ethnicity (black/African American, Hispanic/Latino, white, and other), age (based on the person's age at the end of 2010, with persons assigned to 1 of 5 groups: 13–24, 25–34, 35–44, 45–54, and ≥55 years), transmission category (based on a presumed hierarchical order of probability of infection by sex: for males, male-to-male sexual contact, injection drug use, male-to-male sexual contact and injection drug use, heterosexual contact; for females, heterosexual contact, injection drug use, year of diagnosis (diagnosed before 2008 or in 2008–2010), and gaps in care (had a gap [consecutive VL tests >12 months apart during the 2-year period] vs no gap).

We determined the numbers and percentages of persons in HIV care who had durable viral suppression over 2 years and estimated univariate and multivariate prevalence ratios with confidence intervals, derived from binomial regression models, to identify differences between groups. For viremia copy-years and person-time measures, we used t tests and multivariate regression models to examine group differences. Because the transmission categories were stratified by male and female, a separate sex variable (male vs female) was not included in the multivariate models. All analyses were conducted using SAS version 9.3 (SAS Institute Inc, Cary, North Carolina).

RESULTS

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 were alive at the end of 2013. More than half (425 264, 52.6%) resided in the 17 jurisdictions at the time of diagnosis. The demographic characteristics were similar among the persons from the 17 jurisdictions compared with all persons living with diagnosed HIV (Table 1). There were fewer black/African American and more Hispanic/Latino persons in the 17 jurisdictions compared with persons from the remaining 34 jurisdictions (39.4% vs 45.2%; 24.4% vs 15.4%, respectively). These were the only 2 differences that were >5%.

Table 1.

Characteristics of Persons Aged ≥13 Years With Human Immunodeficiency Virus (HIV) Infection Diagnosed Before 2011 and Alive Through 2013 From 17 US Jurisdictions With Complete Viral Load Reporting Compared With All HIV-Diagnosed Persons Aged ≥13 Years From 50 States and District of Columbia and From 34 Jurisdictions Without Complete Reporting

Sixty-two percent of the 425 264 persons in the 17 jurisdictions (n = 265 264) had at least 1 VL in 2011. The analytic cohort consisted of 238 641 persons with diagnosed HIV in care who had at least 1 VL in 2011 and at least 2 VLs in the 2-year observation period (2012–2013). The median number of VL tests per individual during the 2-year period was 5 (interquartile range, 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 (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).

Table 2.

Characteristics of Persons Aged ≥13 Years With Human Immunodeficiency Virus Infection Diagnosed Before 2011, Alive Through 2013, and in Care With Durable Viral Suppression, 17 US Jurisdictions, 2012–2013

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 of 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; the median was 907 copies/mL (range, 201–10 000 000 copies/mL). In the full analytic cohort, the geometric mean viremia copy-years was 345 and the mean number of days a person spent above 200, 1500, and 10 000 copies/mL were 173, 124, and 84, 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 2 years. By transmission categories, the percentage who had durable viral suppression was significantly higher among men who have sex with men compared with all 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 with 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 with their respective counterparts. There were no differences in univariate and multivariate results.

Table 3.

Cumulative Plasma Human Immunodeficiency Virus (HIV) Burden and Transmission Risk Potential During a 2-Year Observation Period Among Persons Aged ≥13 Years With HIV Infection Diagnosed Before 2011, Alive Through 2013, and in Care, by Selected Characteristics, 17 US Jurisdictions, 2012–2013

Table 4 lists 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 7261, 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, corresponding to 60% of the 2-year period. The mean number of days above 1500 copies and 10 000 copies/mL were 316 and 215, corresponding to 43.2% and 29.5% of the 2-year period. 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 >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 more days during the 2-year period having VLs above 1500 and 10 000 copies/mL.

Table 4.

Cumulative Plasma Human Immunodeficiency Virus (HIV) Burden and Transmission Risk Potential During a 2-Year Observation Period Among HIV-Diagnosed Persons in Care Without Durable Viral Suppression, by Selected Characteristics, 17 US Jurisdictions, 2012–2013

DISCUSSION

We used national HIV surveillance data to assess, for the first time, 3 longitudinal measures of VL dynamics at 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 2 years, indicating sustained treatment success. However, 38% of persons in care did not achieve durable viral suppression, and the viral levels >200 copies/mL were not simply blips but averaged 7261 copies/mL. Those who did not sustain durable viral suppression also spent an average of 60% of the 2-year period with VL above 200 copies/mL as well as a considerable length of time above 1500 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 (ie, no-shows without prior cancellation) were less likely to maintain suppressed VL [13]. To identify patients at risk of not maintaining viral suppression, clinicians might benefit from closer examination of a patient's historical context of clinic attendance, missed visits, and VL patterns (eg, instability, wide swings) in order 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 showed that HIV patients who were not virally suppressed were more likely to receive HIV and/or sexually transmitted disease prevention messages from a healthcare 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 been 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 infection [21] 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 for 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 of 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 period of time relative to estimates based on 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 1 VL test in 2011 as an indicator of at least 1 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 3 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 1 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 VLs 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.

Notes

Disclaimer. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention (CDC).

Financial support. This work was supported by the Division of Human immunodeficiency Virus/AIDS Prevention at the CDC and was not funded by any other organization.

Potential conflicts of interest. M. J. M. has received consulting fees for participation on scientific advisory boards for Bristol Myers Squibb and Gilead Sciences and received grant funding (to the University of Alabama) from Bristol Myers Squibb. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

  • Received April 27, 2016.
  • Accepted June 14, 2016.

References

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