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Trends in CD4 Count Testing, Retention in Pre-ART Care, and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti

  • Serena P. Koenig ,

    skoenig@partners.org

    Affiliations Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti, Division of Global Health Equity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States of America

  • Daphne Bernard,

    Affiliation Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti

  • Jessy G. Dévieux,

    Affiliation AIDS Prevention Program, Florida International University, Miami, FL, United States of America

  • Sidney Atwood,

    Affiliation Division of Global Health Equity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United States of America

  • Margaret L. McNairy,

    Affiliation Center for Global Health, Weill Cornell Medical College, New York, NY, United States of America

  • Patrice Severe,

    Affiliation Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti

  • Adias Marcelin,

    Affiliation Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti

  • Pierrot Julma,

    Affiliation Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti

  • Alexandra Apollon,

    Affiliation Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti

  • Jean W. Pape

    Affiliations Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince, Haiti, Center for Global Health, Weill Cornell Medical College, New York, NY, United States of America

Trends in CD4 Count Testing, Retention in Pre-ART Care, and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti

  • Serena P. Koenig, 
  • Daphne Bernard, 
  • Jessy G. Dévieux, 
  • Sidney Atwood, 
  • Margaret L. McNairy, 
  • Patrice Severe, 
  • Adias Marcelin, 
  • Pierrot Julma, 
  • Alexandra Apollon, 
  • Jean W. Pape
PLOS
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Abstract

Background

High attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is widely reported. Though treatment guidelines have changed to broaden ART eligibility and services have been widely expanded over the past decade, data on the temporal trends in pre-ART outcomes are limited; such data would be useful to guide future policy decisions.

Methods

We evaluated temporal trends and predictors of retention for each step from HIV testing to ART initiation over the past decade at the GHESKIO clinic in Port-au-Prince Haiti. The 24,925 patients >17 years of age who received a positive HIV test at GHESKIO from March 1, 2003 to February 28, 2013 were included. Patients were followed until they remained in pre-ART care for one year or initiated ART.

Results

24,925 patients (61% female, median age 35 years) were included, and 15,008 (60%) had blood drawn for CD4 count within 12 months of HIV testing; the trend increased over time from 36% in Year 1 to 78% in Year 10 (p<0.0001). Excluding transfers, the proportion of patients who were retained in pre-ART care or initiated ART within the first year after HIV testing was 84%, 82%, 64%, and 64%, for CD4 count strata ≤200, 201 to 350, 351 to 500, and >500 cells/mm3, respectively. The trend increased over time for each CD4 strata, and in Year 10, 94%, 95%, 79%, and 74% were retained in pre-ART care or initiated ART for each CD4 strata. Predictors of pre-ART attrition included male gender, low income, and low educational status. Older age and tuberculosis (TB) at HIV testing were associated with retention in care.

Conclusions

The proportion of patients completing assessments for ART eligibility, remaining in pre-ART care, and initiating ART have increased over the last decade across all CD4 count strata, particularly among patients with CD4 count ≤350 cells/mm3. However, additional retention efforts are needed for patients with higher CD4 counts.

Introduction

In September 2015, the World Health Organization (WHO) guidelines changed to recommend antiretroviral therapy (ART) for all HIV-infected patients, as compared to previous guidelines that recommended ART for those with a CD4 count ≤500 cells/mm3, ≤350 cells/mm3 and <200 cells/mm3 [14]. Despite these guideline changes, a substantial proportion of patients continue to initiate ART with advanced AIDS—due either to late presentation for first HIV testing, or return after loss to care. This is associated with poorer immunologic recovery and higher mortality [510]. Timely ART initiation requires effective pre-ART care, which includes early HIV diagnosis, effective linkage to treatment services, and retention in care until ART eligibility. Yet multiple studies have demonstrated that attrition is high at every step of pre-ART care from HIV testing to ART initiation [1121]

Data on temporal trends in rates of completion of ART eligibility staging, pre-ART retention, and ART initiation are limited, and we are aware of no published studies that report on the change in these outcomes over the decade of ART scale-up in resource-poor settings [2224]. We evaluated the temporal trends in CD4 count testing, retention in pre-ART care, and ART initiation rates among a cohort of adult patients from HIV testing through one year of care from 2003 to 2013 at the Haitian Study Group for Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO) clinic in Port-au-Prince, Haiti.

Methods

Settings and Patients

Haiti is the poorest country in the Western Hemisphere, and one of the poorest in the world, ranking 168 out of 187 on the 2014 Human Development Index [25]. Haiti has the highest number of people living with HIV in the Caribbean, the region second most impacted by HIV outside of Africa. Since 1985, the dominant mode of HIV transmission in Haiti has been heterosexual intercourse. The national HIV prevalence has declined from a high of 6.2% in 1993 to 1.9% in 2014 [26].

GHESKIO is a Haitian non-governmental organization (NGO) located in Port-au-Prince, Haiti. It is the oldest and largest provider of HIV services in the Caribbean, having provided voluntary counseling and testing (VCT) for HIV since 1985. There are currently two HIV testing algorithms at GHESKIO. One utilizes the Alere Determine HIV-1/2 Ab test (Alere, Waltham, MA, USA). The other utilizes the HIV ARCHITECT HIV Ag/Ab Combo assay (Abbott Laboratories, Abbott Park, IL, USA). Positive tests are confirmed with an HIV-1/2 Ab test (Colloidal Gold, Shanghai Kehua Bio-engineering Co, Ltd, Shanghai, China). Between 2,000 and 3,000 patients receive positive HIV test results at the main GHESKIO site in downtown Port-au-Prince each year; this represents about 10% of the national total. As of December 2014, Haiti had 166 VCT sites, and 126 public and NGO-based sites provided ART [27]. At the beginning of the study period (March 2003), about 5,000 patients were receiving HIV services every year, and about 100 patients were receiving ART at the main GHESKIO site in Port-au-Prince; this increased to about 5,000 patients on ART at the end of 2008, and nearly 13,500 patients receiving HIV services in 2014, with about 9,000 on ART [27].

At GHESKIO, most patients self-present for HIV testing, rather than being referred from mobile testing centers or outside VCT clinics. Comprehensive HIV care is provided free of charge. All patients >17 years of age who received positive HIV test results between March 1, 2003 and February 28, 2013 were included in the study. Data collection continued until September 1, 2014.

Changes in HIV Care at GHESKIO during the Study Period

HIV care at GHESKIO is provided according to the guidelines of the Haitian Ministry of Health and the WHO [13, 2830]. Throughout the study period, patients were screened for tuberculosis (TB) symptoms at the time of HIV testing. Those with cough for 2 weeks or longer were screened for TB with physician evaluation, sputum microscopy, and chest radiograph. Patients diagnosed with active TB received same-day treatment when possible, and care for both diseases was provided at GHESKIO. Since 1994, isoniazid prophylaxis has been prescribed for patients without active TB who are purified protein derivative (PPD) positive [31]. Trimethoprim-sulfamethoxazole prophylaxisis is initiated for all HIV-infected patients, regardless of CD4 count, at the time that positive HIV test results are provided [32]. CD4 counts are provided on-site at GHESKIO. Patients not yet eligible for ART are scheduled for monthly visits with a clinician for the first 3 months, and then seen every 2 to 3 months. Transportation fees and phone calls for missed visits are provided to patients after they initiate ART.

During the study period, the WHO and Haitian national guidelines changed to recommend earlier treatment. Initially, ART was initiated in patients with WHO stage 4 conditions and/or CD4 count <200 cells/mm3. In 2009, GHESKIO clinicians began initiating ART for patients with WHO stage 3 or 4 conditions and/or CD4 count ≤350 cells/mm3. Of note, GHESKIO was the site of the CIPRA HT 001 study, a randomized trial that was stopped in May 2009, after demonstrating that earlier ART (CD4 count from 200 to 350 cells/mm3) was associated with lower mortality, compared with waiting until CD4 count <200 cells/mm3 or stage 4 disease [33]. In February 2014, the GHESKIO protocol again shifted (following WHO and Haitian national guidelines) to recommend ART for all patients with CD4 count ≤500 cells/mm3 [3, 30].

Data Collection and Statistical Analysis

The following data were extracted from patient electronic medical records (EMRs): demographic information (age, gender, marital status, income, education, and residence zone), dates and results of HIV tests and CD4 counts, dates of initiation of TB treatment and ART, and pre-ART clinic visit dates. Data on risk factors for HIV were not captured. Patients were considered to have TB if they were given a TB diagnosis by the clinician and started on TB treatment. De-identified data were entered into an Excel database (Microsoft, Redmond, WA) and then converted to SAS version 9.2 (SAS Institute, Inc., Cary, NC). Attrition prior to CD4 count was defined as failure to have blood drawn for testing within 12 months after HIV testing, as has been recommended in other publications [34]. For each CD4 count strata (≤200, 201 to 350, 351 to 500, and >500 cells/mm3), we reported: the number of patients who started ART within 12 months of HIV testing; the number who remained in pre-ART care at 12 months, as defined by having at least one pre-ART visit from 9 to 15 months after HIV testing; and the number who were lost to follow up (LTFU), died, or were transferred prior to ART initiation. Due to limited resources, patient tracking activities were not conducted until patients started ART; therefore dates of transfer and death were only ascertained if patients or family members reported this information to the health care providers. Data were collected for 15 months from the time of HIV testing for each patient.

We analyzed trends over time using the Cochran-Armitage trend test, and conducted univariable and multivariable analyses of completion of blood draw for CD4 count, return for CD4 count results, and retention in pre-ART care or ART initiation for each CD4 cell strata using logistic regression. We included the following variables: gender, annual income, education, tuberculosis status at HIV testing, and residence zone (binary variables), study year and marital status (categorical variables), and age (continuous variable). For all multivariable models we included all variables that had been included in the univariable analysis. We used the Wald Confidence Interval (CI) for adjusted odds ratios, and reported 95% CIs. This study was approved by the ethics committees of GHESKIO, Weill Cornell Medical College, and Brigham and Women’s Hospital. It was not feasible to obtain informed consent for this retrospective study, but patient information was anonymized and de-identified prior to analysis.

Results

From March 1, 2003 to February 28, 2013, 24,925 patients >17 years of age received positive HIV test results at GHESKIO. Of these, 15,115 (61%) were women, the median age was 35 years (interquartile range [IQR]: 28 to 43 years), 8,848 (35%) lived in downtown Port-au-Prince, 15,140 (62%) lived on <$US 125/year, and 14,674 (59%) had no education or primary school only; 1,491 (6%) presented with TB at HIV testing (Table 1).

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Table 1. Baseline Characteristics of Patients Newly Diagnosed with HIV (n = 24,925).

https://doi.org/10.1371/journal.pone.0146903.t001

Over the 10-year study period, 15,008 patients (60%) had blood drawn for a CD4 cell count within 12 months of HIV testing, and of these, 5,096 (34%), 3,405 (23%), 2,790 (19%), and 3,717 (25%) patients had a CD4 count of ≤200 cells/mm3, 201 to 350 cells/mm3, 351 to 500 cells/mm3, and >500 cells/mm3, respectively. An additional 1,661 patients had a blood draw for CD4 count more than 12 months after HIV testing, and were excluded from further analyses (Fig 1A). A total of 13,676 patients (91%) returned for CD4 count results, including 4,552 (89%), 3,147 (92%), 2,598 (93%), and 3,379 (91%) for each CD4 cell category, respectively (Fig 1B). The number of patients seeking care at GHESKIO more than doubled from Years 3 to 5; the number who returned for CD4 count test results increased from 787 to 1,802 during this period; it then decreased to 1,671 in Year 10.

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Fig 1. A: Proportion of Patients with Timely, Late, or No Blood Draw for CD4 Count by Year; B: Number and Proportion of Patients Returning for CD4 Count Results by Year.

https://doi.org/10.1371/journal.pone.0146903.g001

The trend in having blood drawn for CD4 count within 12 months of HIV testing increased over time, from 36% in Year 1 to 78% in Year 10 (Cochran-Armitage trend test p<0.0001). The proportion returning for results remained at least 89% across all years (Fig 1A and 1B). The median time from HIV testing to CD4 count decreased from 39 days (IQR: 18 to 113 days) in Year 1 to 10 days (IQR: 7 to 18 days) in Year 10.

Predictors of CD4 Count Completion

In multivariable analysis, factors associated with timely blood draw for CD4 count included later year of HIV test (odds ratio [OR] 1.34; 95% confidence interval [CI]: 1.33–1.36), secondary education (OR 1.37; 95% CI: 1.29–1.45), income >$US 125/year (OR 1.06; 95% CI: 1.00–1.13), older age (OR 1.22; 95% CI: 1.19–1.26), residence outside of downtown Port-au-Prince (OR 1.10; 95% CI: 1.04–1.17), and TB at HIV testing (OR 1.92; 95% CI: 1.69–2.18). Male gender (OR 0.86; 95% CI: 0.81–0.91) and single vs. married status (OR 0.91; 95% CI: 0.85–0.98) were associated with attrition prior to blood draw (Table 2).

In multivariable analysis, factors associated with returning for CD4 count results included secondary education (OR 1.23; 95% CI: 1.09–1.39), income >$US 125/year (OR 1.18; 95% CI: 1.04–1.33), older age (OR 1.09; 95% CI: 1.03–1.16), residence outside of downtown Port-au-Prince (OR 1.16; 95% CI: 1.03–1.30), and TB at HIV testing (OR 2.91; 95% CI: 2.10–4.05). Later year of HIV test (OR 0.97; 95% CI: 0.95–0.99), and male gender (OR 0.86; 95% CI: 0.76–0.97) were associated with attrition prior to returning for results (Table 2).

Trends in Retention in Pre-ART Care and ART Initiation

Among the total cohort of patients who returned for CD4 count results over the study period: 3,705 (27%) were retained in pre-ART care for at least one year; 6,257 (46%) initiated ART within the first year after HIV testing; and 3,298 (24%) were LTFU, 380 (3%) were transferred, and 36 (<1%) were known to have died during the first year after HIV testing, prior to ART initiation. The trend in retention in pre-ART care and ART initiation increased over the study period (Cochran-Armitage trend test, p<0.0001). In Year 1, 33% of patients were retained in pre-ART care, 50% initiated ART, and 17% were LTFU or dead. Outcomes initially worsened, with 28% retained in pre-ART care, 35% initiating ART, and 37% LTFU or dead in Year 5. Outcomes then improved with each subsequent year, such that in Year 10, 18% were retained in pre-ART care, 68% initiated ART, 14% were LTFU, and there were no known pre-ART deaths (Fig 2).

Trends by CD4 Count Strata

During the study period, 4,552 patients had a baseline CD4 count ≤200 cells/mm3, and of these, 270 (6%) were retained in pre-ART care and 3,484 (77%) initiated ART within the year after HIV testing. Six hundred eighty-three patients (15%) were LTFU, 95 (2%) were transferred, and 20 (<1%) died prior to ART initiation. The trend in retention in pre-ART care and ART initiation increased over the study period (Cochran-Armitage trend test, p<0.0001). In Year 10, 5% were retained in pre-ART care, 89% initiated ART, 6% were LTFU, and none were known to have died prior to initiating ART (Fig 2). The median time from CD4 count to ART initiation among patients with CD4 count ≤200 cells/mm3 was 13 days (IQR: 5 to 28 days) in Year 1, and 11 days (IQR: 7 to 17 days) in Year 10.

A total of 3,147 patients had a baseline CD4 count between 201 and 350 cells/mm3, and among these, 538 (17%) were retained in pre-ART care and 1,977 (63%) initiated ART within the first year after HIV testing. Five hundred fifty-six patients (18%) were LTFU, 66 (2%) were transferred, and 10 (<1%) died prior to ART initiation. The trend in retention in pre-ART care or ART initiation increased over the study period (Cochran-Armitage trend test, p<0.0001). In Year 10, 1% of these patients were retained in pre-ART care, 94% initiated ART, 5% were LTFU, and none were known to have died prior to ART initiation (Fig 2).

A total of 2,598 patients had a baseline CD4 count between 351 and 500 cells/mm3, and among these, 1,137 (44%) were retained in pre-ART care and 460 (18%) initiated ART within the first year after HIV testing. Eight hundred ninety-eight patients (35%) were LTFU, 100 (4%) were transferred, and 3 (<1%) died prior to ART initiation. The trend in retention in pre-ART care or ART initiation increased over the study period (Cochran-Armitage trend test, p<0.0001). In Year 10, 26% were retained in pre-ART care, 53% initiated ART, 21% were LTFU, and none were known to have died prior to initiating ART (Fig 2).

A total of 3,379 patients had a baseline CD4 cell count >500 cells/mm3, and of these, 1760 (52%) were retained in pre-ART care and 336 (10%) initiated ART within the first year after HIV testing, One thousand one hundred sixty-one patients (34%) were LTFU, 119 (4%) were transferred, and 3 (<1%) died prior to ART initiation. The trend in retention in pre-ART care or ART initiation increased over the study period (Cochran-Armitage trend test, p = 0.0051). In Year 10, 40% of patients were retained in pre-ART care, 34% initiated ART, 26% were LTFU, and there were no known pre-ART deaths (Fig 2).

Predictors of Pre-ART Retention and ART Initiation

In multivariable analyses (Tables 3 and 4), later year of HIV test was associated with retention in care for patients in all CD4 count strata: CD4 count ≤200 cells/mm3 (OR 1.16; 95% CI: 1.12–1.19); 201 to 350 cells/mm3 (OR 1.24; 95% CI: 1.19–1.29); 351 to 500 cells/mm3 (OR 1.08; 95% CI: 1.05–1.12); and >500 cells/mm3 (OR 1.05; 95% CI: 1.02–1.08). Secondary education was also associated with retention in care for all CD4 strata: CD4 count ≤200 cells/mm3 (OR 1.54; 95% CI: 1.29–1.84); 201 to 350 cells/mm3 (OR 1.27; 95% CI: 1.04–1.55); 351 to 500 cells/mm3 (OR 1.48; 95% CI: 1.24–1.77); and >500 cells/mm3 (OR 1.46; 95% CI: 1.25–1.70). Among patients with low CD4 counts, income >$US 125/year was associated with retention in care: CD4 count ≤200 cells/mm3 (OR 1.33; 95% CI: 1.11–1.59) and 201 to 350 cells/mm3 (OR 1.30; 95% CI: 1.06–1.58). Among patients with high CD4 counts, male gender was associated with pre-ART attrition: CD4 count 351 to 500 cells/mm3 (OR 0.78; 95% CI: 0.65–0.93) and CD4 count >500 cells/mm3 (OR 0.75; 95% CI: 0.63–0.88). TB at HIV testing was associated with pre-ART attrition for patients with CD4 count ≤200 cells/mm3 (OR 0.61; 95% CI: 0.48–0.77), but with improved retention in care for patients with higher CD4 counts: CD4 count 351 to 500 cells/mm3 (OR 2.09; 95% CI: 1.43–3.05) and CD4 count >500 cells/mm3 (OR 2.37; 95% CI: 1.59–3.52).

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Table 3. Predictors of Remaining in Pre-ART Care or Initiating ART among Patients with CD4 Count ≤350 cells/mm3.

https://doi.org/10.1371/journal.pone.0146903.t003

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Table 4. Predictors of Remaining in Pre-ART Care or Initiating ART among Patients with CD4 Count >350 cells/mm3.

https://doi.org/10.1371/journal.pone.0146903.t004

Discussion

We found that completion rates for multiple steps of pre-ART care including assessment for ART eligibility with CD4 count testing, pre-ART retention, and ART initiation have improved over the last decade at the largest HIV clinic in the Caribbean. The proportion of patients having blood drawn for CD4 count within 12 months of HIV testing increased from 36% in Year 1 to 78% in Year 10. We attribute this to a decrease in the median time from HIV testing to CD4 count (39 days in Year 1 to 10 days in Year 10). This was accomplished by implementing a policy to complete CD4 count testing as quickly as possible; CD4 counts are generally ordered the first time an HIV-infected patient sees a GHESKIO physician. Pre-ART retention and ART initiation rates improved over time for patients in all CD4 count strata. Outcomes improved with each subsequent year, except for Years 3 to 5, when the annual number of patients completing CD4 counts more than doubled, and retention temporarily declined. After Year 5, rates of retention and ART initiation progressively improved, and in the Year 10 cohort, only 14% of patients were LTFU.

ART initiation rates were highest among patients with CD4 count ≤350 cells/mm3. In Year 10, 89% of patients with CD4 count ≤200 cells/mm3 and 94% with CD4 count from 201 to 350 cells/mm3 initiated ART within one year of HIV testing. This is higher than ART initiation rates reported from many HIV programs in resource-poor settings. A systematic review from Africa found a median of 68% (range 14 to 84%) of patients who qualified for ART initiated treatment, and a meta-analysis found that 63% of qualifying patients in African studies initiated therapy [16, 17]. For patients with CD4 counts from 201 to 350 cells/mm3 in particular, we attribute the increase in ART initiation rates in part to the change in treatment guidelines, implemented at GHESKIO during Year 7, which made these patients eligible for ART.

Though it improved over time, retention remained lowest among patients with CD4 count >350 cells/mm3. In Year 10, 21% of patients with CD4 count from 350 to 500 cells/mm3 and 26% with CD4 count >500 cells/mm3 were LTFU. The majority of studies from other resource-poor settings document even higher rates of pre-ART attrition in patients with early HIV disease. A systematic review from Africa found a median of 46% (range 31 to 95%) of patients not yet eligible for ART were LTFU during the pre-ART period [16]. In Johannesburg, 74% of patients with CD4 count >350 cells/mm3 did not return within one year for a first medical visit, and only 50% of patients not eligible for ART repeated their CD4 count within the subsequent year [12, 35]. In KwaZulu-Natal only 43% of patients with CD4 count from 351 to 500 cells/mm3 and 35% with CD4 cell count >500 cells/mm3 had a repeat CD4 count within the subsequent 13 months [15]. In Cape Town, 46% of patients not yet eligible for ART returned for a repeat CD4 count after a median time of 8 months [13]. In Cambodia, 60% of patients who didn’t qualify for ART at HIV testing remained in care for one year, compared to 92% of those who initiated ART [36].

Possible explanations for the higher retention rate observed at GHESKIO include more frequent visits and a dedicated pre-ART clinic that opened in 2012. Pre-ART patients are seen monthly for the first quarter, and then at least quarterly. Patients also receive prophylactic medications, including isoniazid and trimethroprim-sulfamethoxazole, regardless of CD4 count, which was found to improve pre-ART retention in care in Africa [37]. Even so, pre-ART retention rates for patients with early HIV disease at GHESKIO remain suboptimal. As in many other HIV programs, GHESKIO does not provide transportation subsidies for patients in pre-ART care [18, 24, 38, 39]. Though resources are very limited, financial enablers may improve retention in care [4043]. Furthermore, in most countries, patients with CD4 count >500 cells/mm3 do not meet immunologic criteria for ART initiation [3]. As countries adopt the recently updated WHO guidelines, which recommend treatment for all HIV-infected patients, the ART initiation rate for this cohort will likely increase, with associated reductions in pre-ART attrition [4].

Throughout the study period, TB at HIV testing was associated with completion of CD4 count, and with retention in care for patients with CD4 counts >350 cells/mm3. We attribute this to fast tracked services, as patients with TB symptoms at HIV testing receive same-day TB testing, and when possible, same-day TB treatment as well. Since HIV and TB treatment services are integrated at GHESKIO, clinicians provide HIV services at the same time they provide TB care. For patients with CD4 count ≤200 cells/mm3, TB at HIV testing was associated with attrition. We attribute this to a higher risk of death in these patients.

Residence outside of downtown Port-au-Prince (where GHESKIO is located) was associated with completion of CD4 count testing, but not with retention in care among those who completed testing. We attribute this in part to the desire of some patients who live near GHESKIO to receive care away from their homes, once they have found out that they are infected, to avoid being recognized; HIV is a stigmatized disease in Haiti. It is also probable that patients who come from farther away have made a special trip to the clinic, so are more likely to complete their lab testing.

Male gender is associated with late HIV testing and more advanced disease at ART initiation [4451], which is strongly associated with poorer outcomes [33]. We found that males were less likely to complete CD4 cell testing, and that among patients with CD4 count >350 cells/mm3, males were less likely to remain in pre-ART care or initiate ART. Studies from other sites have found conflicting results; reports from Mozambique, Nigeria and Kenya [22, 24, 38, 52] detected no association, but studies from Uganda, Malawi and South Africa found that male gender was associated with pre-ART attrition [15, 38, 42]. Innovative outreach efforts for earlier HIV testing and timely ART initiation for males are critical to maximize HIV treatment outcomes.

A major strength of this study is that we include trends in rates of retention in pre-ART care and ART initiation over the decade of expansion of access to ART services. Though our study was conducted at the largest HIV clinic in the Caribbean, the results may not be generalizable to other HIV clinics in resource-poor settings. Our study was also limited by the inability to determine vital status for patients who were LTFU, though in a prior study that included patient tracking, we found that only 12% of patients lost prior to ART initiation had received care in a different HIV clinic [53].

Conclusions

In summary, completion rates for multiple steps in pre-ART care including assessment of ART eligibility with CD4 count testing, pre-ART retention, and ART initiation have improved over the last decade across all CD4 strata, and are particularly high among patients with CD4 count ≤350 cells/mm3. However, additional retention efforts are needed to help patients with higher CD4 counts, males, younger patients, and patients with poor socio-economic status to remain in care. Implementation of the recent WHO recommendation for universal treatment may improve retention among patients with early HIV disease.

Author Contributions

Conceived and designed the experiments: SPK DB JGD SA MLM PS AM PJ AA JWP. Performed the experiments: SPK DB JGD SA MLM PS AM PJ AA JWP. Analyzed the data: SPK DB JGD SA MLM PS AM PJ AA JWP. Wrote the paper: SPK DB JGD SA MLM PS AM PJ AA JWP. Patient care: DB AA PS JWP.

References

  1. 1. Rapid Advice—Antiretroviral therapy for HIV infection in adults and adolescents, November 2009. Geneva, Switzerland, World Health Organization 2009. Accessed October 22, 2015 at: http://www.who.int/hiv/pub/arv/rapid_advice_art.pdf.
  2. 2. Antiretroviral therapy for HIV infection in adults and adolescents: Recommendations for a public health approach; 2006 revision. Geneva, Switzerland: World Health Organization, 2006. Accessed October 22, 2015 at: http://www.who.int/hiv/pub/guidelines/adult/en/.
  3. 3. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection. Recommendations for a Public Health Approach. June 2013. Geneva, Switzerland: World Health Organization, 2013. Accessed October 22, 2015 at: http://www.who.int/hiv/pub/guidelines/arv2013/en/.
  4. 4. Guidelines on When to Start Antiretroviral Therapy and on Pre-Exposure Prophylaxis for HIV. September 2015. Geneva, Switzerland: World Health Organization, 2015. Accessed October 22, 2015 at: http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/.
  5. 5. Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006,367:817–824. pmid:16530575
  6. 6. Nash D, Wu Y, Elul B, Hoos D, El Sadr W. Program-level and contextual-level determinants of low-median CD4+ cell count in cohorts of persons initiating ART in eight sub-Saharan African countries. AIDS 2011,25:1523–1533. pmid:21750418
  7. 7. Palombi L, Marazzi MC, Guidotti G, Germano P, Buonomo E, Scarcella P, et al. Incidence and predictors of death, retention, and switch to second-line regimens in antiretroviral- treated patients in sub-Saharan African Sites with comprehensive monitoring availability. Clin Infect Dis 2009,48:115–122. pmid:20380075
  8. 8. May M, Boulle A, Phiri S, Messou E, Myer L, Wood R, et al. Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes. Lancet 2010,376:449–457. pmid:20638120
  9. 9. Nglazi MD, Lawn SD, Kaplan R, Kranzer K, Orrell C, Wood R, et al. Changes in programmatic outcomes during 7 years of scale-up at a community-based antiretroviral treatment service in South Africa. J Acquir Immune Defic Syndr 2011,56:e1–8. pmid:21084996
  10. 10. Boulle A, Van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, Mathee S, et al. Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 2010,24:563–572. pmid:20057311
  11. 11. Larson BA, Brennan A, McNamara L, Long L, Rosen S, Sanne I, et al. Lost opportunities to complete CD4+ lymphocyte testing among patients who tested positive for HIV in South Africa. Bull World Health Organ 2010,88:675–680. pmid:20865072
  12. 12. Larson BA, Brennan A, McNamara L, Long L, Rosen S, Sanne I, et al. Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa. Trop Med Int Health 2010,15 Suppl 1:43–47. pmid:20586959
  13. 13. Kranzer K, Zeinecker J, Ginsberg P, Orrell C, Kalawe NN, Lawn SD, et al. Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa. PLoS One 2010,5:e13801. pmid:21072191
  14. 14. Losina E, Bassett IV, Giddy J, Chetty S, Regan S, Walensky RP, et al. The "ART" of linkage: pre-treatment loss to care after HIV diagnosis at two PEPFAR sites in Durban, South Africa. PLoS One 2010,5:e9538. pmid:20209059
  15. 15. Lessells RJ, Mutevedzi PC, Cooke GS, Newell ML. Retention in HIV care for individuals not yet eligible for antiretroviral therapy: rural KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr 2011,56:e79–86. pmid:21157360
  16. 16. Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med 2011,8:e1001056. pmid:21811403
  17. 17. Mugglin C, Estill J, Wandeler G, Bender N, Egger M, Gsponer T, et al. Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis. Trop Med Int Health 2012,17:1509–1520. pmid:22994151
  18. 18. Tayler-Smith K, Zachariah R, Massaquoi M, Manzi M, Pasulani O, van den Akker T, et al. Unacceptable attrition among WHO stages 1 and 2 patients in a hospital-based setting in rural Malawi: can we retain such patients within the general health system? Trans R Soc Trop Med Hyg 2010,104:313–319. pmid:20138323
  19. 19. Bassett IV, Regan S, Chetty S, Giddy J, Uhler LM, Holst H, et al. Who starts antiretroviral therapy in Durban, South Africa?… not everyone who should. AIDS 2010,24 Suppl 1:S37–44. pmid:20023438
  20. 20. Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strategies for prevention of HIV infection. Clin Infect Dis 2011,52:793–800. pmid:21367734
  21. 21. Marks G, Gardner LI, Craw J, Crepaz N. Entry and retention in medical care among HIV-diagnosed persons: a meta-analysis. AIDS 2010,24:2665–2678. pmid:20841990
  22. 22. Mulissa Z, Jerene D, Lindtjorn B. Patients present earlier and survival has improved, but pre-ART attrition is high in a six-year HIV cohort data from Ethiopia. PLoS One 2010,5:e13268. pmid:20949010
  23. 23. April MD, Walensky RP, Chang Y, Pitt J, Freedberg KA, Losina E, et al. HIV testing rates and outcomes in a South African community, 2001–2006: implications for expanded screening policies. J Acquir Immune Defic Syndr 2009,51:310–316.
  24. 24. Aliyu MH, Blevins M, Parrish DD, Megazzini KM, Gebi UI, Muhammad MY, et al. Risk factors for delayed initiation of combination antiretroviral therapy in rural north central Nigeria. J Acquir Immune Defic Syndr 2014,65:e41–49. pmid:23727981
  25. 25. United Nations Development Programme Human Development Reports—2014. Accessed on October 13, 2015 at: http://hdr.undp.org/en/content/human-development-index-hdi-table.
  26. 26. UNAIDS Country Report, Haiti, 2014. Accessed on October 13, 2015 at: http://hdr.undp.org/en/content/human-development-index-hdi-table.
  27. 27. Monitoring, Evaluation, and Surveillance Interface. Haiti. Accessed October 22, 2015 at: http://www.mesi.ht.
  28. 28. Manuel de Normes de Prise en Charge Clinique et Thérapeutique des Adultes et Adolescents Vivant avec le VIH. Ministère de la Santé Publique et de la Population (MSPP), République d’Haiti, 2008. Accessed on October 13, 2015 at: http://www.who.int/hiv/pub/guidelines/haiti_art.pdf?ua=1.
  29. 29. Antiretroviral Therapy for HIV Infection in Adults and Adolescents. Recommendations for a Public Health Approach, 2010 Revision, World Health Organization, Geneva, Switzerland, 2010. Accessed October 22, 2015 at: http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf.
  30. 30. Manuel de Normes de Prise en Charge Clinique et Thérapeutique des Adultes et Adolescents Vivant avec le VIH. Ministère de la Santé Publique et de la Population (MSPP), République d’Haiti, 2013. Accessed October 13, 2015 at: http://mspp.gouv.ht/site/downloads/Normes de Prise en Charge Clinique et Th%C3%A9rapeutique des adultes et adolescents vivant avec le VIH Sida 2013.pdf.
  31. 31. Pape JW, Jean SS, Ho JL, Hafner A, Johnson WD Jr. Effect of isoniazid prophylaxis on incidence of active tuberculosis and progression of HIV infection. Lancet 1993,342:268–272. pmid:8101302
  32. 32. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents, and adults. Recommendations for a public health approach. World Health Organization, 2006. Accessed October 22, 2015 at: http://www.who.int/hiv/pub/guidelines/ctxguidelines.pdf.
  33. 33. Severe P, Juste MA, Ambroise A, Eliacin L, Marchand C, Apollon S, et al. Early versus standard antiretroviral therapy for HIV-infected adults in Haiti. N Engl J Med 2010,363:257–265. pmid:20647201
  34. 34. Fox MP, Larson B, Rosen S. Defining retention and attrition in pre-antiretroviral HIV care: proposals based on experience in Africa. Trop Med Int Health 2012,17:1235–1244. pmid:22863075
  35. 35. Fox MP, Shearer K, Maskew M, Meyer-Rath G, Clouse K, Sanne I. Attrition through Multiple Stages of Pre-Treatment and ART HIV Care in South Africa. PLoS One 2014,9:e110252. pmid:25330087
  36. 36. van Griensven J, Sopheak T, Aseffa Y, Van Damme W, Lynen L. Attrition of HIV-infected individuals not yet eligible for antiretroviral treatment: do we care? Trans R Soc Trop Med Hyg 2010,104:690–692; author reply 692–693.
  37. 37. Kohler PK, Chung MH, McGrath CJ, Benki-Nugent SF, Thiga JW, John-Stewart GC. Implementation of free cotrimoxazole prophylaxis improves clinic retention among antiretroviral therapy-ineligible clients in Kenya. AIDS 2011,25:1657–1661. pmid:21673562
  38. 38. Zachariah R, Tayler-Smith K, Manzi M, Massaquoi M, Mwagomba B, van Griensven J, et al. Retention and attrition during the preparation phase and after start of antiretroviral treatment in Thyolo, Malawi, and Kibera, Kenya: implications for programmes? Trans R Soc Trop Med Hyg 2011,105:421–430. pmid:21724219
  39. 39. Micek MA, Gimbel-Sherr K, Baptista AJ, Matediana E, Montoya P, Pfeiffer J, et al. Loss to follow-up of adults in public HIV care systems in central Mozambique: identifying obstacles to treatment. J Acquir Immune Defic Syndr 2009,52:397–405. pmid:19550350
  40. 40. Govindasamy D, Kranzer K, Ford N. Strengthening the HIV cascade to ensure an effective future ART response in sub-Saharan Africa. Trans R Soc Trop Med Hyg 2014,108:1–3. pmid:24284954
  41. 41. Assefa Y, Van Damme W, Mariam DH, Kloos H. Toward universal access to HIV counseling and testing and antiretroviral treatment in Ethiopia: looking beyond HIV testing and ART initiation. AIDS Patient Care STDS 2010,24:521–525. pmid:20672972
  42. 42. Amuron B, Namara G, Birungi J, Nabiryo C, Levin J, Grosskurth H, et al. Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda. BMC Public Health 2009,9:290. pmid:19671185
  43. 43. Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AIDS 2012,26:2059–2067. pmid:22781227
  44. 44. Cornell M, Schomaker M, Garone DB, Giddy J, Hoffmann CJ, Lessells R, et al. Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study. PLoS Med 2012,9:e1001304. pmid:22973181
  45. 45. Madec Y, Laureillard D, Pinoges L, Fernandez M, Prak N, Ngeth C, et al. Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia. AIDS 2007,21:351–359. pmid:17255742
  46. 46. MacPherson P, Moshabela M, Martinson N, Pronyk P. Mortality and loss to follow-up among HAART initiators in rural South Africa. Trans R Soc Trop Med Hyg 2009,103:588–593. pmid:19012940
  47. 47. Mutevedzi PC, Lessells RJ, Heller T, Barnighausen T, Cooke GS, Newell ML. Scale-up of a decentralized HIV treatment programme in rural KwaZulu-Natal, South Africa: does rapid expansion affect patient outcomes? Bull World Health Organ 2010,88:593–600. pmid:20680124
  48. 48. Hawkins C, Chalamilla G, Okuma J, Spiegelman D, Hertzmark E, Aris E, et al. Sex differences in antiretroviral treatment outcomes among HIV-infected adults in an urban Tanzanian setting. AIDS 2011,25:1189–1197. pmid:21505309
  49. 49. Mills EJ, Bakanda C, Birungi J, Chan K, Hogg RS, Ford N, et al. Male gender predicts mortality in a large cohort of patients receiving antiretroviral therapy in Uganda. J Int AIDS Soc 2011,14:52. pmid:22050673
  50. 50. Kumarasamy N, Venkatesh KK, Cecelia AJ, Devaleenol B, Saghayam S, Yepthomi T, et al. Gender-based differences in treatment and outcome among HIV patients in South India. J Womens Health (Larchmt) 2008,17:1471–1475.
  51. 51. Auld AF, Mbofana F, Shiraishi RW, Sanchez M, Alfredo C, Nelson LJ, et al. Four-year treatment outcomes of adult patients enrolled in Mozambique's rapidly expanding antiretroviral therapy program. PLoS One 2011,6:e18453. pmid:21483703
  52. 52. Moon TD, Burlison JR, Blevins M, Shepherd BE, Baptista A, Sidat M, et al. Enrolment and programmatic trends and predictors of antiretroviral therapy initiation from president's emergency plan for AIDS Relief (PEPFAR)-supported public HIV care and treatment sites in rural Mozambique. Int J STD AIDS 2011,22:621–627. pmid:22096045
  53. 53. Noel E, Esperance M, McLaughlin M, Bertrand R, Devieux J, Severe P, et al. Attrition from HIV Testing to Antiretroviral Therapy Initiation among Patients Newly Diagnosed with HIV in Haiti. J Acquir Immune Defic Syndr 2012.