The number of new locally diagnosed HIV persons in-care increased from 46 in 2001 to 76 in 2010 with the corresponding incidence rate increasing from 4.4 to 5.8/100,000 (Table 2). The number of transfer patients previously diagnosed with HIV elsewhere but new to the population increased from 38 to 88 (incidence rate increasing from 3.6 to 6.7/100,000). Overall, the yearly number of new patients followed at the SAC (ie, either newly diagnosed or moved into the region) increased from 84 to 164 (incidence rate of HIV patients under care increasing from 8.0 to 12.5/100,000).
Churn and Community Viral Load in 2009
Table 4 shows the effects of churn on CVL for the year 2009. Patients enter the cohort either by having a new local HIV diagnoses (category 2), being diagnosed and treated outside the region and moving into the cohort (category 3), or former SAC patients who returned to HIV care after an absence (category 4). Patients leave the cohort by moving outside the region (category 5), disengaging in-care, or by being LTFU (category 6).
Continuous patients followed during the entire year (category 1) accounted for 78.7% of the population and 81% of all VL tests performed. They, however, only contributed 29.5% of the total CVL. The mean VL per patient was 10,575 copies per milliliter (SD = 0–277 copies per milliliter). Six-eight percent achieved mean undetectable VL throughout the year, and 81% were suppressed.
Individuals newly entering the population (ie, categories 2 and 3) account for 11.4% of all active patients but contribute 43% to the total CVL. New locally diagnosed patients (category 2), although 6.6% of the cohort population, account for 37.5% of the total CVL. The mean VL for these patients was 162,260 copies per milliliter (SD = 213,976); 95% of newly diagnosed patients had mean detectable VLs over the 12-month period in 2009. Patients presenting with a CD4 < 350 mm3 had higher mean VLs (329,856 copies per milliliter; SD = 316,779) than patients presenting with higher CD4 counts (81,886 copies per milliliter; SD = 77,456; data not shown).
Transfer patients (category 3) comprised 4.8% of all patients (43% of new patients) and contributed 5.5% to the total CVL. Thirty-nine percent of these patients had unsuppressed VLs for the year. The mean VL per patient was 34,509 copies per milliliter (SD = 27,458).
Former SAC patients returning to care (category 4), although only 4.2% of the population, contributed 16.6% of the CVL. Eighty-two percent of these patients were not suppressed. Their mean VL was 107,261 copies per milliliter (SD = 96,834). Seventy-five percent of the patients in this category had previously been listed at LTFU from SAC; >80% of the LTFU patients reported that they had remained in the community while they were discontinued from care. For patients who received some care elsewhere outside the region and then returned, 35% had mean VLs >200 copies per milliliter (mean VL = 38,837 copies per milliliter; SD = 25,345).
Patients can also leave the study population by moving or disengaging from care (LTFU). VLs for these patients were obtained before leaving. These patients comprise 5.7% of the total population but 10.9% of the total CVL. Patients who state they are moving and where they will be transferring to (category 5) had mean VLs of 25,337 copies per milliliter (SD = 34,259); however, 51% had unsuppressed mean VLs before leaving. Patients who became LTFU during 2009 (category 6) contributed only 3.1% toward population but 8.5% to the total CVL. When we examined their last VLs from 2008, we found that, before leaving care, they had a mean VL of 90,998 copies per milliliter (SD = 101,723) with 75% having detectable VLs highly suggestive of a major underestimate of LTFUs, true contribution to CVL.
Despite HAART use increasing in our population to 81%, and with the proportion of all patients with a suppressed VL increasing from 49% to 79%, total CVL (ie, in-care VL) did not significantly decrease over 10 years. No significant decline in new “local” HIV diagnoses was observed throughout the decade. Our results differ somewhat from those of other studies,12–19 but we suspect that the disparity may be due to the definition of community, different methods for determining CVL, variations on how new HIV diagnoses are reported, and the effects of churn.
Defining community remains problematic and contributes to the potential effect of selection and sampling basis as discussed by Miller et al.20 Most communities are neither isolated nor homogeneous entities. Communities have often been defined by lifestyle (eg, intravenous drug users17), or geographically by city,14,18 province, state, or country.15,16,19 Limiting a community as only those patients under continuous care may reduce some of the bias; however, it may mislead in measuring the preventative effects of HAART by reflecting neither the wider population living with HIV nor the population dynamics. For example, in our study, patients under continuous care (category 1) could be viewed as community, albeit not a homogeneous one. This community has a high proportion of patients on HAART (87%) with only 14% experiencing detectable viremia in 2009. Since 2005, the number of patients in this community increased from 768 to 1110, mean VL decreased from 16,219 to 12,737 copies per milliliter, and total CVL has been relatively stable (11,430,176 to 10,595,519 copies per milliliter; data not shown). However, if this community is used as the measure of successful treatment strategies, it does not account for why new HIV diagnoses have not decreased significantly.
The reporting of CVL also remains an important issue.20 We used the mean VL per patient as suggested by Das et al14 but wonder if this is the appropriate measurement. For example, if all VL measurements for all patients are used, it may better reflect the actual VL in the community but it creates statistical bias as some patients with repeated measurements contribute more to the total CVL than others. Using only the mean VL per patient, as we do here, may reduce bias but may not be representative of the actual VL within the population. Using only the highest VL, a patient reported during a time period (eg, Montaner et al15) may overrepresent CVL given fluctuating annual VLs in many patients. For example, we found that 1 in 5 patients with undetectable mean VLs had at least 1 detectable VL during the year. Miller et al20 point out that the type of CVL measurement selected can underestimate or overestimate the CVL, and which approach (ie, mean VL, most recent VL, and the highest VL) is the better reflection of total CVL remains uncertain.
A further issue is the definition of what exactly constitutes new HIV diagnoses. Ideally, only new locally diagnosed HIV infections should be included as they would reflect the local epidemic; however, new HIV infections and new HIV diagnoses are not necessarily the same. Changing numbers of diagnoses can be the result of greater or lesser HIV testing in the region; they may represent previously undiagnosed chronic HIV infections; or they may represent movement into the community by individuals who acquired HIV elsewhere but were not diagnosed. Conversely, individuals locally infected with HIV may leave the region without being diagnosed and hence are not captured as a new HIV infection. Defining exactly what constitutes a new HIV infection within a community is critical for assessing CVL as numbers can be quite different depending on how, where, and who reports new HIV diagnoses. We looked at all individuals with a new positive HIV test and reported to Public Health in 2009 to see who accessed HIV care. Nineteen of 102 individuals (18.2%) with positive tests did not access care before 2012. Using 102 rather than 83 new locally diagnosed HIV individuals would increase the incidence rate from 6.4 to 7.86/100,000. We do not however know if these were legitimate new diagnoses or previously diagnosed individuals living locally or even in transit taking an HIV test for unknown reasons.
Hence, we found that the number of new HIV infections in our population can vary significantly depending on which definition is used, and this, in turn, impacts CVL calculations. New locally diagnosed HIV patients, although comprising <7% of the total community, contributed 33% of the total CVL. It is well known that acute and early HIV infection is associated with greater transmissibility2,25 contributing a much larger percentage toward the total known CVL. Additionally, patients first diagnosed elsewhere who move into the region, and hence may be considered new HIV diagnoses for the purposes of CVL, contributed an additional 5% of the total CVL. Expanding or contracting the definition of new HIV diagnosis can either support or weaken (ie, underestimate or overestimate) CVL depending on the definition applied.
Churn seems to have a substantial impact on the calculation of CVL (Fig. 1). Migrating patients and patients who disengage from care tend to have a higher mean VL22 with fewer patients achieving suppressed VL levels. LTFU patients, for example, had high levels of detectable VL (82%) before leaving care. These individuals do not contribute significantly to the measured CVL in 2009 (3%) and their absence from care actually lowers the CVL, but if they remain in the community, they potentially can contribute significantly to new HIV infections. For instance, we found that 75% of the returning patients who were LTFU had detectable VLs upon returning to care and contributed more to the measured CVL than did patients moving into the region.
Our centralized care structure and geography allow us to examine many of the components of CVL in our population. We, however, like every other center, are limited in determining the “true” CVL in that we do not know who is HIV infected but undiagnosed. Studies26–30 have estimated that between 20% and 30% of all HIV-infected individuals remain undiagnosed. In addition, Kelley et al31 discuss the importance of determining the proportion of persons within the total population that are unsuppressed and how they contribute to CVL; however, how much these individuals are contributing to the CVL is not measurable (by definition as a VL test result is absent) but given that at least 82% of patients with an HIV-positive test accessed HIV care in our study, and that newly diagnosed patients contributed almost 33% of the total CVL that is known, inclusion of these individuals (ie, imputing of VL data) would most likely substantially increase the total CVL. As such, the data we present are an underestimation of the true CVL within the community. We also do not directly address the assumptions listed in Table 1, although testing these assumptions should be a priority before CVL is widely incorporated; the assumptions may or may not, by themselves, be supportable.
Over the past decade, despite increasing use of HAART, and fewer patients in-care with detectable VLs, there has been little or no change in either the total CVL (ie, in-care VL) or the number of new HIV diagnoses. These data may result from differential transmissibility of high-risk individuals as discussed by Miller et al,20 or may also in part reflect the aspects of the “churn” effect. Communities and social networks are not “closed” and are susceptible to movement between communities, however defined.
We strongly agree with more widespread and routine testing for HIV infection coupled with accession of care in a timely fashion. The provision of HAART to reduce VLs is important both for treatment of an individual and to reduce their infectivity to others.31,32 Retention in-care remains a critical issue.33,34 We feel however that, although CVL is an intriguing measurement, the use of CVL as a benchmark indicator of “success” is, at present, premature and must be used with caution. Our CVL results suggest that in developed world populations effort should be focused on finding undiagnosed patients and engaging them in lifelong care.
The authors wish to thank Karen Ko and Danette Mohagen at the Southern Alberta Clinic for their assistance in maintaining the SAC database. They thank Marcy Thompson and Dr. Judy MacDonald for providing surveillance data of HIV tests conducted in southern Alberta. They also thank the anonymous reviewers for their comments and suggestions.
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Keywords:© 2013 by Lippincott Williams & Wilkins
HIV/AIDS; community viral load; viral load testing; health policy; Canada