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Epidemiology and Prevention

Attrition and Opportunities Along the HIV Care Continuum: Findings From a Population-Based Sample, North West Province, South Africa

Lippman, Sheri A. PhD, MPH*; Shade, Starley B. MPH, PhD*; El Ayadi, Alison M. ScD, MPH; Gilvydis, Jennifer M. MPH; Grignon, Jessica S. MPH‡,§; Liegler, Teri PhD; Morris, Jessica MA*; Naidoo, Evasen MSocSc§; Prach, Lisa M. PhD, MPH*; Puren, Adrian PhD¶,#; Barnhart, Scott MD, MPH‡,§

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1, 2016 - Volume 73 - Issue 1 - p 91-99
doi: 10.1097/QAI.0000000000001026

Abstract

BACKGROUND

South Africa has the largest HIV antiretroviral treatment (ART) program in the world,1 including decentralized ART distribution from primary health clinics and expanded ART eligibility.2,3 Despite notable progress, there are an estimated 200,000 AIDS-related deaths each year,4 and only half of those qualifying for ART are currently receiving treatment, which is provided free of charge through the public health system.5 The “cascade” of attrition along the HIV care continuum from diagnosis of infection through viral suppression6,7 in South Africa must be characterized to target programming and improve the proportion of people who know their status, engage in care, initiate and maintain treatment, and achieve viral suppression to stem further transmission.8–10

Currently, there are limited data providing a comprehensive characterization of the HIV care continuum in South Africa. National seroprevalence data from 2012 indicated that although 65.0% of the population had ever been tested for HIV, only 37.8% of HIV-positive men and 55.0% of HIV-positive women were aware of their HIV status.11 Available data on linkage to care and retention after HIV diagnosis come primarily from data on clinical cohorts. Systematic reviews of clinical cohort data across sub-Saharan Africa estimate that 59%–66% of people with known HIV status have been assessed for ART eligibility and of those eligible, less than half returned for follow-up care.7,12 Patient retention after ART initiation is estimated at 75% and 65% across sub-Saharan Africa after 1 and 3 years, respectively.13,14 Finally, little is known about population-based viral suppression rates in sub-Saharan Africa. Although data from the South African National Health Laboratory Service indicate that ∼75%–80% of ART-initiated patients achieve viral suppression, only 40% of ART patients have viral load data available.15

Population-based data are scarce but extremely important not only to understand where attrition occurs but also to estimate the complete population burden of disease and the gaps in engagement in clinical care among all people living with HIV. We conducted a population-based survey to characterize the HIV care continuum in a rural district of North West Province, South Africa, an area of the country with substantial burden of disease and little available data.

METHODS

Study Setting

Data were collected from January to March 2014 in Lekwa-Teemane and Greater Taung subdistricts of North West Province, Republic of South Africa. The area is largely rural, with >46.0% of the population living in poverty, compared with a national average of 39.9%.16 The province has the fourth highest HIV prevalence in South Africa, estimated at 20.3% among adults 15–49 years11 and 29.7% in the antenatal population.17

Sampling and Recruitment

We employed multistage cluster sampling. Twenty-three enumeration areas (EAs) in each subdistrict were selected proportionate to size by Statistics South Africa using 2011 census data. The sampling frame was developed in September 2013 through enumeration of dwelling units (DU) in each EA; fieldworkers recorded the names, ages, and sex of DU residents. According to census criteria, residence was defined as sleeping in the DU an average of ≥4 nights per week. Statistics South Africa then randomly selected 36 inhabited DUs from each EA (1561 DUs in total) for inclusion in the sample and randomly selected 1 adult (18–49 years) per DU for participation. When more than one DU resident met eligibility criteria (58% of DUs), a second individual was listed as a replacement. Replacement household members were only approached if the first participant was no longer eligible.

Local, trained fieldworkers approached each assigned DU up to 5 times to locate the selected individual for study participation. Eligibility criteria included being 18–49 years, residing in the home, and able to provide consent (not visibly high, drunk, or with a discernable cognitive impairment). When a participant was located, fieldworkers confirmed eligibility for the study, obtained written informed consent, and conducted a survey by computer-assisted personal interviewing in a private location at the participant's home in the participant's language of choice (English, Xhosa, Afrikaans, or Setswana). The survey included questions on demographic characteristics, HIV testing history, health services use, and health behaviors.

HIV and CD4 T-cell Testing and Dried Blood Spot Collection

After the survey, point-of-care HIV rapid antibody testing and pre- and posttest counseling were performed by trained community health workers. HIV serostatus was determined by HIV-1/2 antibody rapid testing using the Alere Determine HIV-1/2 rapid test with finger-stick capillary blood (Alere, Bedfordview, South Africa), and, if reactive or indeterminate, confirmed using the First Response HIV 1-2.0 Rapid Whole Blood Test (Premier Medical Corporation Ltd, Daman, India). Participants testing positive or indeterminate were offered point-of-care CD4 testing using the Alere Pima CD4 analyzer (Alere Inc., Waltham, MA) using 25 μL of capillary blood, following the manufacturer's instructions. The participant was provided with the test result, counseled on the result's meaning, and referred for care at the local health care facility if needed. Participants with HIV positive or indeterminate results were asked to provide finger-prick blood for dried blood spots (DBSs) using a Munktell filter card (Ahlstrom Munktell, Helsinki, Finland) for viral load testing. Participants who declined HIV rapid testing in their home were also asked to provide blood for DBS for laboratory HIV diagnosis (serology: enzyme-linked immunosorbent assay confirmed with Western blot) and viral load testing and offered a study number to call for the results. DBS cards were dried, stored with desiccant at ambient temperature, transported to the testing laboratory within 6 days of collection, and stored at −70°C. Viral load testing was performed using the COBAS AmpliPrep for sample preparation and COBAS TaqMan HIV-1 2.0 test (Roche Applied Science, Pleasanton, CA; lower limit of quantification 400 copies per milliliter).

Written informed consent was obtained for each study procedure; the survey was the only required component. Participants were compensated for their time with an airtime voucher worth ∼$5 USD after completion of all consented procedures. Study procedures were pilot tested in a neighboring subdistrict before data collection, including a quality assurance program for measurement of viral load using DBS.18 The protocol was approved by the Committee for Human Research at the University of California, San Francisco; the Human Subjects Division at University of Washington; the Human Sciences Research Council Research Ethics Committee in South Africa; the Policy, Planning, Research, Monitoring and Evaluation Committee for the North West Provincial Department of Health; and the Centers for Disease Control and Prevention's Center for Global Health, Human Research Protection.

Measures

Elements of the HIV Care Continuum were defined as follows:

  1. Undiagnosed or newly diagnosed: HIV-positive participants with no reported previous testing or reporting a previous negative test.
  2. Linked to care: reported ever seeing a nurse or doctor for HIV care.
  3. Ideal linkage: saw a care provider and completed CD4 testing within 3 months of diagnosis.
  4. Retained in care:
    • Participants clinically designated as ART eligible: reported being currently on ART and seeing an HIV care provider every 3 months in the past year.3
    • Participants not yet qualifying for ART: reporting seeing a care provider and receiving CD4 testing in the past year.19
  5. ART adherent: reported taking >90% of their prescribed antiretroviral medication in the past month with no lapse of ≥7 days within the past year.20–22
  6. Viral suppression: viral load of <5000 copies per milliliter. We used this conservative threshold as there is no definitive cut-point using DBS.23 We also examined thresholds of <1000 and <3000 copies per milliliter.

Previous HIV testing behavior was self-reported. Measured CD4 counts among those individuals identified by HIV rapid test as positive were dichotomized at 350 cells/μL, reflecting the 2013 South African ART guidelines, which were in effect during the data collection period.24

Analysis

All analyses were weighted to account for sample design. Weights were created using the inverse probability of selection at each stage (EA, DU, and person) and adjusted for nonresponse to reflect the municipality, age group, and sex distributions within the target population.25

We calculated weighted sample sizes, proportions, and 95% confidence intervals (CIs) to describe overall and sex-specific participant demographic characteristics, HIV testing, HIV prevalence, and HIV care engagement. Care continuum outcomes were estimated and presented in 2 ways: (1) among the complete HIV-positive population, to provide a comprehensive vision of the care continuum in this population-based sample, and (2) conditionally, including those previously diagnosed with HIV, with each step in the continuum dependent on achieving the previous step, to enable comparison with clinical cohort data. To evaluate sex-specific differences in the HIV care continuum, we estimated χ2 statistics using the second-order Rao and Scott correction for bivariate analyses,26F statistics for age group differences, and generalized linear regression modeling (glm). HIV prevalence, ART eligibility, and DBS (viral load) results were adjusted using multiple imputation to account for nonparticipation or missing data (see Supplemental Digital Content, http://links.lww.com/QAI/A816). All analyses were performed using Stata 12 (StataCorp, College Station, TX).

RESULTS

Sample Characteristics

Forty-six EAs were visited for enumeration (Fig. 1). Three EAs were excluded as fieldworkers were not granted access to the areas. Of the remaining 1527 DUs, 98.5% were approached during 7 weeks of recruitment. Contact was made at 91.7% of DUs, yielding 1146 eligible individuals, of whom 1048 (76.0% of contacted DUs; 91.0% of eligible participants) consented to take part in the study. Four individuals were incorrectly recruited, resulting in a total analytic sample of 1044. The most common reasons for ineligibility were no longer residing in the DU (85.4%) and being unable to provide consent (6.0%). Overall, those who were not located, not eligible, or declined participation were more likely to be male (51.6%) than female (48.4%).

FIGURE 1.
FIGURE 1.:
Participant recruitment, enrollment, and data collection, North West Province, South Africa.

The final weighted sample reflects the gender and age distribution of the subdistricts (Table 1). Almost all participants were South African citizens or permanent residents (99.4%), and just over half (53.9%) were employed in the past year. Two-thirds had not completed secondary school and about one-quarter of the sample experienced household food insecurity, defined as having gone to bed hungry some to most of the time in the past month.

TABLE 1.
TABLE 1.:
Participant Demographic Characteristics, North West Province, South Africa, 2014

HIV Prevalence, CD4, and HIV Testing

Among 745 respondents undergoing either rapid HIV testing or HIV testing using DBS (71.7% of the sample), 183 individuals tested positive. An additional 35 respondents who declined testing reported positive serostatus, resulting in a total of 218 HIV-positive participants. Point-of-care CD4 tests were performed on 158 (94.1%) participants with an HIV-positive rapid test result. DBS were collected from 157 (93.5%) participants who tested HIV positive or indeterminate in the field, 51 participants who declined rapid testing, and 1 was collected from an HIV-negative participant in error, resulting in a total of 209 DBS collected.

Overall 20.0% (95% CI: 13.7 to 26.2) of men and 26.7% (95% CI: 22.1 to 31.4) of women were HIV positive (Table 2); prevalence was higher among female than male participants in every age group. Prevalence in male participants increased with age, peaking at 40–49 years; prevalence in female participants peaked at 30–39 years. Although 68.9% of men (95% CI: 61.8 to 75.1) and 89.2% of women (95% CI: 84.2 to 92.7) reported having tested previously, there were a substantial number of new HIV diagnoses, particularly among men. Among those newly diagnosed, approximately one-third of women and men reported having tested negative in the previous 12 months; one-third of men reported having never tested (Table 2). CD4 cell count varied significantly by sex; CD4 counts were lower for men; this was true among both newly diagnosed men and those who already knew their serostatus (data not shown).

TABLE 2.
TABLE 2.:
HIV Prevalence, Testing History, and CD4 Results by Sex, North West Province, South Africa, 2014

HIV Continuum of Care

Population-Based: Among all HIV-Positive People

There was major attrition along the HIV continuum of care for the full HIV-positive population, with the most significant drop occurring at the gateway to the care continuum: testing, particularly for men (Fig. 2; Table S1). Over half (51.6%, 95% CI: 39.5 to 63.5) of men and one-quarter (24.3%, 95% CI: 14.9 to 36.9) of women identified as HIV positive were previously unaware of their serostatus. The proportion of those who eventually linked to care was similar to the proportion of those previously diagnosed, suggesting that those who are aware of their HIV-positive status will eventually seek care. However, we observed additional attrition associated with retention, treatment, and viral suppression. Only 33.1% (95% CI: 21.4 to 47.3) of HIV-positive men and 58.4% (95% CI: 49.2 to 67.1) of women were retained in care, of whom the majority had been initiated on ART (Fig. 2, hashed area represents the proportion of those retained classified as pre-ART). Although 33.1% (95% CI: 21.8 to 46.8) and 53.5% (95% CI: 42.6 to 64.1) of HIV-positive men and women reported adherence to medication, only 21.6% (95% CI: 7.6 to 35.7) and 50.0% (95% CI: 39.4 to 60.7) of HIV-positive men and women, respectively, had attained viral suppression, using a conservative threshold of 5000 copies per milliliter (Fig. 2).

FIGURE 2.
FIGURE 2.:
Continuum of HIV care among all those HIV positive, North West Province, South Africa.

Conditional Cascade: Among Those Achieving Each Previous Step

Next, we examined attrition across the care continuum conditioning on each previous step, among those who already knew their positive HIV status (Fig. 3; Table S2). The majority of people living with HIV, 98.8% of women (95% CI: 96.0 to 99.6) and 90.8% of men (95% CI: 80.3 to 96.0), were ever linked to care, though <60% linked to care within 3 months of diagnosis (ideal linkage). Among those who ever linked to care, 75.2% (95% CI: 52.0 to 89.5) of men and 78.1% (95% CI: 68.1 to 85.7) of women were retained in care; retention being higher among those who were ART eligible. The vast majority of men (97.2%, 95% CI: 80.7 to 99.7) and women (91.6%, 95% CI: 80.3 to 96.7) retained in care on ART reported adhering to their medication; however, only 28.8% (95% CI: 4.7 to 52.9) of men and 59.7% (95% CI: 43.3 to 76.1) of women achieved viral load <5000 copies per milliliter. We used a higher threshold for determining viral suppression with DBS23 than that which is recommended for plasma. Thus, population viral suppression may be overestimated. Using cut-offs of <1000 and <3000 copies per milliliter, respectively, 25.7% (95% 12.5–39.0) and 40.1% (95% CI: 24.4 to 55.6) of the population retained on ART would be classified as virally suppressed (Table S2). Of note, <50% of participants who should have had a viral load conducted (all those on ART for at least 6 months) reported past viral load testing.

FIGURE 3.
FIGURE 3.:
Conditional continuum of HIV care, North West Province, South Africa.

DISCUSSION

These results provide a comprehensive picture of engagement in HIV care from diagnosis to viral suppression in a geographic area with little previous research but extremely high burden of disease. Based on the full HIV-positive population, it is quite clear that the greatest gap in engagement occurs at HIV diagnosis, indicating a critical need for improving case detection, particularly among men. Less than half of HIV-positive men and 3-quarters of HIV-positive women were aware of their serostatus before our survey. Previous population-based seroprevalence data point to similar rates of reported HIV testing and an even higher proportion of undiagnosed infections,11,27 particularly among men.27–29 HIV prevalence in our sample was also similar to that reported for adults in the North West Province in the 2012 national survey (20.3%)11 and for women in the national antenatal survey (29.7%).17 With continued losses along the continuum of care at linkage, retention, and ART adherence, a resulting 50% of women and 21% of men living with HIV in the region are virally suppressed under a best case scenario (using a liberal definition of suppression). This portends continued high rates of transmission in the area unless uptake of testing and treatment initiation improve rapidly and rates of viral suppression are greatly improved.

We also assessed the conditional continuum of care, beginning with those aware of their HIV-positive status, to compare our findings with data from clinical cohorts. We found remarkably similar patterns: among survey participants who were previously aware of their positive serostatus, almost all reported having seen a care provider for HIV, though only 54% reported being assessed for ART eligibility within 3 months of diagnosis.30,31 This estimate, though based on self-report, is consistent with data from South African clinical cohorts, which have found that between 50% and 70% of HIV-positive patients undergo CD4 staging within 3 months.12,19,32,33 Our findings regarding retention in care also correspond with estimates from South African clinical cohorts, despite different methods of measurement. Unlike studies that monitor retention within a clinic, we assessed frequency of care without detailed case history tied to a particular clinic. For patients who were known to be eligible for ART, 81.7% reported remaining on ART and receiving care at least every 3 months in the past year (as clinics provide ART for 1–3 month increments). South African clinical cohorts have documented retention among ART-initiated patients of 75% at 1 year,19 81% remaining on treatment for 2 years,34 and data from the National Health Indicators Report indicate that 82% of initiated patients remained on treatment at 3 years (among those reported into the national system).15 Pre-ART retention, also referred to as stage 2 retention,30 in our study was low: 68% of women and no men were retained in this stage (no men were previously diagnosed before treatment eligibility, an indication that men do not seek testing until they are already ill). Studies from Cape Town, Johannesburg, and Kwa-Zulu Natal similarly documented that 45%–57% of those not ART eligible returned for a subsequent CD4 test in ∼1-year time frames, with men being less likely than women to return for subsequent testing.19,32,35

Our findings demonstrate high reported adherence, but low rates of viral suppression, indicating a potential bias in self-reported adherence data, which could be due to social desirability bias or overreporting of medication adherence, or due to medication failure. Although the effect of social desirability bias would likely overestimate the proportion of those “adherent” to care, ART adherence is not always overreported. Whereas preexposure prophylaxis clinical trial data among women in Africa indicate extreme overreporting of medication adherence,36 instances of underreporting usage of antiretrovirals in large trials have also been documented.37 A recent population-based HIV survey in South Africa found high agreement between self-reported ART intake and blood-tested ART exposure (κ = 91.9%). Self-report and blood test discrepancies were demonstrated in both directions, such that just >7% of those reporting ART intake had negative blood tests and similar numbers reporting no ART intake had positive blood tests for ART.38 Further analysis of the DBS samples should shed light on drug exposure.

We used a conservative threshold for defining viral suppression because of the sample matrix used, as cellular HIV DNA contributes to copy number when using whole blood instead of blood plasma samples.23 By using 5000 copies per milliliter as a threshold, we run the risk of overestimating viral suppression. If we lower the threshold to 3000 copies per milliliter or even to 1000 copies, viral suppression among all those on ART is estimated at 40.1% and 25.7% as opposed to 51.8%. Viral suppression in this study is below national targets and estimates from other recent population-based studies39 but aligns with estimates based on population-level projections from national data.40 Data from the National Health Laboratory Service suggest that viral suppression (defining viral suppression as <400 copies per milliliter plasma) ranges from 52% to 75% for North West Province, depending on the district.15 However, National Health Laboratory Service viral load information is available for less than half of ART patients; which is consistent with reported rates of viral load testing in our sample. This may indicate that treatment failure is not being properly monitored and could lead to high rates of HIV-1 drug resistance in this rural population. Additionally, food insecurity, which was prevalent in this sample, has been shown to be an independent predictor of incomplete viral suppression after adjustment for ART adherence.41

Our data have several limitations and a number of strengths. First, linkage, retention, and adherence are based on self-report and not linked to clinical records; participants may not recall dates and/or overreport clinic attendance and adherence. Second, those who are in care are more likely to survive and therefore more likely to be included in our estimates; this survivor bias may lead to inflated estimates of engagement in care. However, our findings on the proportion of those linked to and retained in care are quite similar to findings from clinical cohorts using documented treatment history and accounting for death. Third, our sample cannot account for populations who are highly mobile, unlikely to be included in survey data and more likely to drop out of care.42 Both in- and outmigration in North West Province is extremely common;43 in our data, ∼13% of the original sample were no longer at the residence only 6 months after the area was enumerated. One strength of these data is the potential to capture more inclusive measures of engagement to care, in that our estimates of linkage and retention are not impacted by mobility between clinics or erroneous classification of patients as out of care when they are, in fact, deceased.12 Further, it should be noted that prevalence may be underestimated in our data, despite adjustments for nonresponse, as HIV-positive individuals are more likely to refuse testing.44,45

CONCLUSIONS

Increasing ART coverage can significantly lower the risk of new HIV infections in South Africa.46 However, treatment expansion will only extend prevention gains if infected individuals are identified early in their HIV disease, enter into care rapidly, remain in care, adhere to ART, and achieve viral suppression. These population-based data provide a comprehensive picture of the HIV care continuum in the North West Province and should be used to inform targeted programming. Although attrition occurs along all steps of the cascade, the most urgent need is for improved HIV detection, particularly among men. Evidence-based, male-targeted programming, including programs that address male norms that dissuade care seeking and work- or community-based programming outside of the clinic environment, is sorely needed to improve testing uptake, frequency, and early linkage to care. The low proportion of those achieving viral suppression also requires urgent attention. At present, population viral load is still too elevated to expect treatment as prevention to achieve its potential impact in this region. Future research to understand the discrepancies between reported adherence and viral suppression is warranted.

ACKNOWLEDGMENTS

We thank the team at I-TECH South Africa, from data collectors to site supervisors, for study implementation. We thank Elsie Raphela, Charles Koenaite, Lebogang Ntswane, and the combination prevention team for community entry, logistics, and assistance in training the fieldwork teams. We acknowledge our collaborators at Statistics South Africa for sample enumeration and LifeLine Mafikeng for provision of community health workers. We thank the North West Provincial Department of Health, Dr. Ruth Segomotsi Mompati District Department of Health, Lekwe Teemane and Greater Taung Sub-district Department of Health, and the Provincial Research Committee for ongoing support of this project. We thank the participants for their generosity and willingness to be a part of this study.

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Keywords:

South Africa; HIV testing; HIV care continuum; adherence; retention; linkage

Supplemental Digital Content

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