Virologic suppression among HIV-infected US Air Force members in a highly-structured programme with free access to care

Abstract

Summary

The United States Air Force HIV programme has several features that may enhance antiretroviral therapy outcomes, including free access to healthcare and mandatory clinical visits every six months at a single centre. We evaluated viral load suppression (<50 copies/ml) after 12 months of initial antiretroviral therapy, with extension to 18 and 24 months. Active duty Air Force members were categorised by year of antiretroviral therapy initiation: 2000–2005 (n = 95, 36.1%) and 2006–2011 (n = 168, 63.9%). The median months from HIV diagnosis to initial antiretroviral therapy were shorter in the 2000–2005 group (2.4, IQR 1.2–5.9) compared with the 2006–2011 group (12.6, IQR 2.6–29.0; p < 0.001). Viral load suppression was greater in the 2006–2011 group compared with the 2000–2005 group at 12 months (93.2% versus 78.6%, p = 0.002) and 18 months (91.8% versus 80.3%, p = 0.03), and trended higher at 24 months (90.8% versus 82.5%; p = 0.15). Factors associated with viral load suppression at 12 months in multivariate models included antiretroviral therapy initiation during 2006–2011 (OR 5.22, 95% CI 1.50–18.18) and CD4 count at antiretroviral therapy initiation (OR 2.29, 95% CI 1.19–14.43 per 100 cells/µl increase). Structured programmes that minimise traditional barriers to care combined with the use of contemporary antiretroviral therapy regimens can achieve clinic-wide viral load suppression in >90% of patients.

Keywords

HIV treatment antiretroviral therapy HAART AIDS Air Force military continuum of care treatment cascade

Introduction

The potency, convenience, and tolerability of contemporary antiretroviral therapy (ART) regimens have made the treatment goal of viral load (VL) suppression attainable for most HIV-infected individuals in developed countries. Although VL suppression should theoretically approach 100% for adherent patients with no evidence of transmitted or acquired drug resistance, the rates of VL suppression remain suboptimal in clinical practice.^1,2 The greatest success has been demonstrated in the highly-structured environment of clinical trials, with recent studies reporting VL suppression in 85–90% with first-line regimens in treatment-naïve patients.^3,4 Virologic outcomes are improving in many clinical practice settings, however recent reports range from 70 to 78% which is considerably lower than VL suppression observed in clinical trials.^5–7

The reasons for these shortcomings can be partly explained by examining issues along the HIV cascade of care.¹ Successful treatment and long-term survival of HIV-infected persons depend on a continuum of healthcare services including diagnosis of HIV infection, linkage and retention in HIV care, and ongoing HIV prevention education and interventions.² However, each step in the care continuum has multiple barriers and challenges with considerable downstream impact. For example, it is estimated that just 66% of all HIV-infected persons in the US are linked to care and 37% are receiving regular HIV care.⁸ Factors that negatively affect access and retention in care include lack of health insurance, homelessness, unemployment, and lower education level.⁸ HIV care programmes that seek to improve overall health of HIV-infected persons and reduce HIV transmission must aggressively reduce leakage along the continuum of care.⁹

The United States Air Force (USAF) clinical HIV programme provides comprehensive HIV education, care, and treatment, including the provision of antiretrovirals, at no cost to the patient. All active-duty USAF members are screened for HIV infection every 2 years, and those testing positive are then evaluated at a single military treatment facility, with mandatory clinical visits every six months thereafter while continuing on active-duty service. Many factors that typically hinder the clinical response to ART in most cohorts, such as access to care, health insurance, and intravenous drug use, are minimised or eliminated in the military setting. We evaluated whether the clinical HIV programme in the USAF, a programme with reduced barriers to HIV care, would translate to improved virologic suppression compared with reports from other clinical settings. We divided the 12-year study into two time periods according to year of ART initiation (2000–2005 and 2006–2011) to account for changes in treatment guidelines and availability of newer antiretrovirals, to include single-tablet regimens. Since an increase in virologic suppression has been reported in recent studies, we hypothesised that a higher proportion of VL suppression would be observed during the later time period in our cohort.

Methods

All active-duty USAF members diagnosed with HIV infection have mandatory clinical evaluations at the San Antonio Military Medical Center (SAMMC) every six months, with all travel and costs managed by the USAF. Clinical visits include HIV disease staging, laboratory evaluation, physical examination, immunisations, and HIV education. We conducted a retrospective review of clinical data collected from active duty USAF members diagnosed with HIV infection between 1 January 2000 and 31 December 2011 and who had completed at least six months of continuous ART in the USAF programme. Data were collected through 31 December 2012. This retrospective study was approved by the SAMMC Institutional Review Board.

The primary outcome of interest was the achievement of virologic suppression defined as <50 copies/ml 12 months after ART initiation. The analysis was extended to 18 and 24 months post-ART for those with available data. Assessment of VL suppression at the six-month time point was not included since treatment was often delayed several weeks for HIV genotype results to return and some patients were not taking ART for at least six months at this visit. If two or more values were available, the value closest to the time point was used. To account for differences in treatment guideline recommendations for ART initiation as well as differences in efficacy and toxicity of treatment regimens during the study period, patients were divided into two groups based on year of ART initiation: 2000–2005 and 2006–2011. For further analyses, calendar year of HIV diagnosis and calendar year of starting ART were categorised in two-year intervals to illustrate variations in ART timing relative to HIV diagnosis and differences in CD4 cell counts at ART initiation, as these characteristics were highly influenced by guideline changes during the study period. The diagnosis of AIDS was defined according to the 1993 Centers for Disease Control and Prevention (CDC) criteria.¹⁰ Logistic regression was used to compute odds ratios for variables associated with achieving virologic suppression. Effects with p-values ≤0.3 were eligible for inclusion in multivariate models. The Mann–Whitney–Wilcoxon test, Pearson Chi square test, or Fisher’s exact test were used when appropriate. P-values <0.05 were considered statistically significant. SAS 9.3 was used to perform all statistical analyses (SAS Institute, Cary, NC).

Results

A total of 309 USAF members diagnosed with HIV infection initiated ART during the study period, with 263 (85.1%) retained on active duty and included in this analysis. The remaining 46 (14.9%) patients were excluded due to separation from military service prior to six months of ART treatment and HIV care was transitioned to outside the USAF programme. Of the 263 patients included in the analysis, 95 (36.1%) initiated ART in 2000–2005 and 168 (63.9%) in 2006–2011 (Table 1). The median interval between the last documented negative HIV test and first positive HIV test was 17.5 months (IQR 10.7–26.1) and did not differ significantly between treatment-era groups. All patients, whether stationed in or outside the US, received their initial HIV programmatic evaluations a median 39 (IQR, 26–54) days after HIV diagnosis. Patients were predominantly young men with subtype B infection in both groups. Most patients were European American or African American, and the median ages at HIV diagnosis and ART initiation were 28 and 31 years, respectively. The median CD4 cell count at HIV diagnosis was significantly higher in the 2006–2011 group (479 cells/µl, IQR 352–600) compared with the 2000–2005 group (393 cells/µl, IQR 291–580; p = 0.02), but median plasma VL at diagnosis did not differ (4.42 log₁₀ copies/ml, IQR 3.96–4.89 versus 4.52 log₁₀ copies/ml, IQR 3.73–4.88; p = 0.77, respectively). See Table 1, VL at HIV diagnosis, for reference.

Table 1.

Characteristics of study participants.

		Calendar Year of ART Initiation
Characteristic	All	2000–2005	2006–2011	P Value*
No. of participants, no. (%)	263	95 (36.1)	168 (63.9)
Male, no. (%)	258 (98.1)	94 (99.0)	164 (97.6)	0.66
Ethnicity, no. (%)^a	235	94	141	0.65
European American	103 (43.8)	53 (45.7)	60 (42.5)
African American	96 (40.9)	40 (42.6)	56 (39.7)
Hispanic	24 (10.2)	7 (7.4)	17 (12.1)
Others	12 (5.1)	4 (4.3)	8 (5.7)
Age at HIV diagnosis (years)	28 (24–36)	30 (24–37)	28 (23–36)	0.17
Age at ART initiation (years)	31 (25–38)	31 (25–38)	31 (25–38)	0.91
Time from last negative test to HIV diagnosis (months)	17.5 (10.7–26.1)	18.5 (9.9–31.1)	17.4 (10.9–24.9)	0.24
Time from HIV diagnosis to care entry (days)	39 (26–54)	39 (27–54)	38 (26–55)	0.70
Time from HIV diagnosis to ART initiation (months)	5.9 (1.9–22.3)	2.4 (1.2–5.9)	12.6 (2.6–29.0)	<0.001
HIV Subtype B (%)^b	170 (97.1)	27 (93.1)	143 (98.0)	0.19
AIDS diagnosed at ART initiation, no. (%)	37 (14.6)	19 (21.6)	18 (10.8)	0.02
HBV/HCV co-infection at ART initiation, no. (%)	11 (4.2)	2 (2.1)	9 (5.4)	0.34
CD4 count at HIV diagnosis (cells/µl)	461 (323–599)	393 (291–580)	479 (352–600)	0.02
CD4 count at ART initiation (cells/µl)	355 (272–455)	364 (269–471)	348 (277–449)	0.73
VL at HIV diagnosis (log₁₀ copies/ml)	4.44 (3.93–4.88)	4.52 (3.73–4.88)	4.42 (3.96–4.89)	0.77
VL at ART initiation (log₁₀ copies/ml)	4.71 (4.32–5.00)	4.79 (4.43–5.00)	4.67 (4.21–5.00)	0.76
Initial ART regimen, no. (%)				<0.001
NNRTI-based	150 (57.0)	62 (65.3)	88 (52.4)
PI-based	51 (19.4)	17 (17.9)	34 (20.2)
INSTI-based	46 (17.5)	0 (0.0)	46 (27.4)
Other (3NRTI)	16 (6.1)	16 (16.8)	0 (0.0)

AIDS: acquired immunodeficiency syndrome; ART: antiretroviral therapy; HBV: hepatitis B; HCV: hepatitis C; HIV: human immunodeficiency virus; INSTI: integrase strand transfer inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; VL: viral load.

Unless otherwise specified all data are median and interquartile range (IQR).

*P values were computed with the use of Mann–Whitney Wilcoxon, Chi square test or Fisher’s exact test.

^aTwenty-eight patients did not report race/ethnicity data.

^bOne hundred and seventy-five patients reported HIV subtypes and were dichotomised as subtype B or other.

At ART initiation, the median CD4 cell count and plasma VL at ART initiation did not differ statistically by treatment era: 364 cells/µl (IQR 269–471) for 2000–2005 versus 348 cells/µl (IQR 277–449) for 2006–2011, p = 0.73 and 4.79 log₁₀ copies/ml (IQR 4.43–5.00) versus 4.67 log₁₀ copies/ml (IQR 4.21–5.00), p = 0.76, respectively. Non-nucleoside reverse transcriptase inhibitor-based regimens were most common in both groups; however, integrase strand transfer inhibitor (INSTI)-based regimens were prescribed for >25% of patients in the 2006–2011 treatment era, during which time raltegravir, the first INSTI, became available for clinical use. The median time from HIV diagnosis to ART initiation was significantly shorter in the 2000–2005 group (2.4 months, IQR 1.2–5.9) compared with the 2006–2011 group (12.6 months, IQR 2.6–29.0; p < 0.001). Since CD4 counts at the start of ART were no different among treatment groups, the longer time to ART initiation in the 2006–2011 group can be attributed to significantly higher CD4 count at HIV diagnosis which remained above treatment thresholds for a longer period compared with the 2000–2005 group (Figure 1). Examination of the time from HIV diagnosis to ART initiation in two-year intervals showed a significant trend towards more rapid initiation of ART later in the study period, with the shortest time to ART initiation observed for persons diagnosed during 2010–2011 (Figure 1(a)). By calendar year of ART initiation, a larger proportion of patients were treated in the second half of the study period with the greatest increase noted during 2004–2005 (Figure 1(b)). CD4 counts at ART initiation decreased for persons diagnosed during 2000–2005, followed by an upward trend with a peak in 2008–2009 (Figure 1(c)). CD4 counts at ART initiation were higher during calendar years 2000–2001 and then declined during the mid-2000s before rising again in 2008–2009, mirroring changes in HIV treatment guidelines during this period (Figure 1(d)).

Figure 1.

Time from HIV diagnosis to commencing ART in months and CD4 cell count at time of ART initiation by calendar year. Panels (a) and (b) depict time (months) from date of HIV diagnosis to date of starting ART by every two calendar years of HIV diagnosis and ART initiation, respectively. Panels (c) and (d) depict CD4 count at ART initiation by year of HIV diagnosis (panel (c)) or by year of ART initiation (panel (d)) in two-year intervals. P-values for pairwise comparisons and number of participants in each group were shown.

Over the study period, 178 of 202 (88.1%) patients had achieved VL suppression 1 year after ART initiation (Table 2), which improved over time: 78.6% in 2000–2005 compared with 93.2% in 2006–2011, p = 0.002. A similar pattern was observed at 18 and 24 months for the 2000–2005 and 2006–2011 groups: 80.3% versus 91.8% (p = 0.03) and 82.5% versus 90.8% (p = 0.15), respectively. A significant trend in VL suppression by calendar year of ART initiation was observed at 12, 18, and 24 months post-ART (Figure 2). Median CD4 cell gains at 12, 18, and 24 months after ART initiation were 208 (IQR 119–339), 229 (IQR 112–375), and 239 (IQR 123–356) cells/µl, respectively, for all patients and did not differ between groups.

Table 2.

Virologic suppression and CD4 cell gains after ART initiation.

Time since ART	Outcome	All	2000–2005	2006–2011	P value
12 months
	Virologic suppression, no. (%)	178/202 (88.1)	55/70 (78.6)	123/133 (93.2)	0.002
	CD4 cell gain (cells/µl)	208 (119–339)	215 (87–316)	207 (130–346)	0.22
18 months
	Virologic suppression, no. (%)	154/176 (87.5)	53/66 (80.3)	101/110 (91.8)	0.03
	CD4 cell gain (cells/µl)	229 (112–375)	185 (72–382)	240 (154–368)	0.43
24 months
	Virologic suppression, no. (%)	141/161 (87.6)	52/63 (82.5)	89/98 (90.8)	0.15
	CD4 cell gain (cells/µl)	239 (123–356)	224 (124–356)	248 (123–353)	0.79

ART: antiretroviral therapy.

Virologic suppression defined as <50 copies/ml.

Unless otherwise specified all data are median and interquartile range (IQR).

*P values were computed with the use of Mann–Whitney Wilcoxon or Chi square test.

Figure 2.

Proportion of patients with VL <50 copies/ml by calendar year of ART Initiation. Bar charts describe distribution of patients achieved virologic suppression at the 12th month (panel (a)), 18th month (panel (b)), and 24th month (panel (c)) since starting ART by every two calendar years indicated in the bar graphs. P-trends and numbers for all groups at each time point are shown.

Factors associated with VL suppression at 12 months in univariate analyses included initiating ART during 2006–2011 (odds ratio [OR] 3.73, 95% CI 1.54–9.04; p = 0.004) and CD4 cell count at ART initiation (OR 1.88, 95% CI 1.24–2.85 for each increase of 100 cells/µl; P = 0.003) (Table 3). Initiating ART during 2006–2011 remained significantly associated with VL suppression at 18 months but not at 24 months, whereas higher CD4 count at ART initiation was no longer significant after 12 months. In multivariate modelling, we adjusted for covariates of race/ethnicity, age at ART initiation, time from last-negative to first-positive HIV test, time from diagnosis to ART initiation, VL at ART initiation, AIDS diagnosis at ART initiation, HBV/HCV co-infection and subtype B infection. Initiating ART during 2006–2011 (OR 5.22, 95% CI 1.50–18.18; p = 0.001) and CD4 cell count at ART initiation (OR 2.29, 95% CI 1.19–14.43 for each increase of 100 cells/µl; p = 0.01) were significantly and independently associated with VL suppression at 12 months but not thereafter. The choice of initial ART regimen had no significant effect on achieving virologic suppression after adjusting for covariates.

Table 3.

Factors associated with virologic suppression during ART.

	12 months post-ART		18 months post-ART		24 months post-ART
Models	Odds Ratio (95%CI)	P value	Odds Ratio (95%CI)	P value	Odds Ratio (95%CI)	P value
Univariate Models
Ethnicity
African American versus European American	0.60 (0.23–1.55)	0.29	1.03 (0.38–2.80)	0.96	0.91 (0.33–2.47)	0.85
Hispanic versus European American	1.02 (0.20–5.16)	0.98	1.21 (0.24–6.11)	0.82	2.67 (0.31–22.65)	0.37
Other versus European American	1.75 (0.33–∞)	0.63	1.61 (0.19–14.01)	0.66	1.67 (0.19–14.65)	0.65
Age at ART initiation	0.99 (0.94–1.05)	0.88	1.00 (0.94–1.06)	0.98	1.04 (0.98–1.11)	0.22
Time from last negative to first HIV-positive test, each increase of one month	0.98 (0.96–1.01)	0.15	1.00 (0.97–1.03)	0.97	1.01 (0.98–1.04)	0.60
Time from HIV diagnosis to ART initiation, each increase of one month	1.00 (0.98–1.02)	0.95	1.01 (0.98–1.04)	0.46	1.02 (0.99–1.06)	0.22
Calendar year of ART initiation, 2006–2011 versus 2000–2005	3.73 (1.54–9.04)	0.004	2.75 (1.11–6.86)	0.03	2.09 (0.81–5.38)	0.13
CD4 count at HIV diagnosis, each increase of 100 cells/µl	1.39 (1.07–1.81)	0.01	1.30 (1.00–1.69)	0.05	1.12 (0.88–1.44)	0.36
CD4 count at ART initiation, each increase of 100 cells/µl	1.88 (1.24–2.85)	0.003	1.08 (0.79–1.47)	0.63	0.94 (0.71–1.25)	0.68
VL at HIV diagnosis, each increase of 1 log₁₀ copies/ml	0.94 (0.56–1.57)	0.80	0.77 (0.42–1.41)	0.39	1.24 (0.75–2.04))	0.41
VL at ART initiation, each increase of 1 log₁₀ copies/ml	1.04 (0.51–2.11)	0.92	0.70 (0.31–1.60)	0.39	1.44 (0.71–2.93)	0.30
AIDS diagnosis at ART initiation, yes versus no	0.41 (0.14–1.23)	0.11	1.77 (0.39–8.08)	0.46	0.83 (0.22–3.12)	0.78
HBV or HCV co-infection, yes versus no	0.94 (0.11–8.00)	0.96	0.34 (0.06–1.85)	0.21	0.26 (0.05–1.54)	0.14
HIV subtype B versus other	1.54 (0.00–9.44)	0.99	4.04 (0.34–47.42)	0.27	4.55 (0.38–54.27)	0.23
Initial ART regimen
PI-based versus NNRTI-based	0.44 (0.16–1.16)	0.09	0.47 (0.17–1.34)	0.16	0.57 (0.18–1.83)	0.34
INSTI-based versus NNRTI-based	1.74 (0.37–8.18)	0.48	1.54 (0.32–7.38)	0.59	0.74 (0.14–3.73)	0.71
3NRTI versus NNRTI-based	0.51 (0.10–2.61)	0.42	0.41 (0.08–2.25)	0.31	0.12 (0.03–0.54)	0.005
INSTI based versus PI-based	4.00 (0.79–20.36)	0.09	3.25 (0.62–17.09)	0.16	1.29 (0.22–7.47)	0.77
3NRTI versus PI-based	1.16 (0.21–6.47)	0.86	0.88 (0.15–5.17)	0.88	0.22 (0.04–1.09)	0.06
Multivariate Models
Model 1: Calendar year of ART initiation, 2006–2011 versus 2000–2005	5.22 (1.50–18.18)	0.001	2.99 (0.89–10.01)	0.07	2.33 (0.47–11.51)	0.30
Model 2: CD4 count at ART initiation, each increase of 100 cells/µl	2.29 (1.19–14.43)	0.01	1.59 (0.89–2.86)	0.12	1.44 (0.77–2.67)	0.25

AIDS: acquired immunodeficiency syndrome; ART: antiretroviral therapy; CI: confidence interval; HBV: hepatitis B virus; HCV: hepatitis C virus; INSTI: integrase strand transfer inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; NRTI: nucleoside reverse transcriptase inhibitor; PI: protease inhibitor; VL: viral load.

Logistic regression was used to compute the likelihood (odds ratio) of achieving virologic suppression at the 12th, 18th, and 24th month after starting ART. Multivariate models adjusted for ethnicity, age at ART, time from negative to positive HIV test, time from diagnosis to ART initiation, VL at ART initiation, AIDS diagnosis at ART initiation, HBV/HCV co-infection, and HIV subtype B.

Discussion

The primary goal of ART is suppression of HIV viraemia, which ultimately results in immune reconstitution and improved clinical outcomes. A high proportion of VL suppression on ART was achieved in the USAF active-duty military population with HIV infection, especially in those who initiated ART in more recent years. Successful HIV treatment outcomes are likely explained not only by improved convenience and tolerability of contemporary ART regimens, but also by the unique aspects of the USAF clinical HIV programme and characteristics of the active duty population. As a result of a combination of these factors, VL suppression was achieved and maintained for greater than 24 months in over 90% of HIV-infected members continuing on active duty in the USAF between 2006 and 2011.

There are many challenges to achieving successful clinical care and management of HIV-infected persons. The most important step in the continuum of care for HIV infection is diagnosis. In the US, approximately 15.8% of HIV-infected adults remain undiagnosed¹¹ and account for approximately half of new HIV transmissions.¹² Although opt-out testing advocated by the CDC has led to an increase in early HIV diagnosis, only an estimated 9.6% of persons aged 18–64 years reported recent HIV testing in 2010.² In contrast, the USAF mandates HIV testing every two years for all active-duty members, as well as before and after military deployments. This mandatory testing structure results in early diagnosis of HIV infection for active-duty members. Consequently, USAF members typically have preserved CD4 cell counts at diagnosis. For example, the median CD4 count at diagnosis was 479 cells/µl in the period of 2006–2011, which is considerably higher than the average of 336 cells/µl for newly-diagnosed persons in the general US population reported in 2011.¹³ The combination of early diagnosis with a low proportion of AIDS events and relatively preserved CD4 counts results in improved long-term prognosis for the majority of USAF members diagnosed with HIV while on active duty. Continued emphasis on HIV screening for populations at risk is essential to not only reduce HIV transmission, but also to allow for early initiation of ART which will likely contribute to improved treatment outcomes in HIV-infected individuals.

In most clinical settings, engagement in care remains a significant problem.¹⁴ A study in Boston, Massachusetts demonstrated a high proportion of virologic suppression (89.9% at one year) in patients who were already engaged in care at the time of HIV diagnosis; however, only 39% of all cases identified initiated care.¹⁵ Although active-duty USAF members are stationed at a large number of military bases nationally and internationally, all newly-diagnosed members are evaluated at a single clinical site. Clinical recommendations are often communicated to healthcare providers worldwide prior to engagement in the USAF clinical HIV programme, and patients undergo initial programmatic evaluation approximately one month after diagnosis. Retention in care is also critical in order to achieve full benefits of ART, and visit non-adherence has been independently associated with greater cumulative VL during the first two years of care.¹⁶ In addition, patients with missed visits in the first year after ART initiation have experienced more than twice the rate of long-term mortality than patients who attended all scheduled appointments.¹⁷ Although it is not feasible to have ‘mandatory’ clinic visits every six months in non-military settings, it is reasonable to surmise that that this continued linkage to care contributed to the high proportion of VL suppression in our population. Although AIDS diagnoses are declining, the vast majority of USAF members with AIDS are able to continue on active duty because of successful treatment with ART and its beneficial effect on their immune status and overall health.

Significant improvements have been made in the pharmacology and pharmacokinetics of antiretroviral agents. Newer ART regimens have greater potency, longer half-lives, reduced metabolic effects, and improved adverse effect profiles, all of which contribute to higher efficacy observed in recent clinical trials. For example, the SPRING-2 trial of integrase inhibitor-based regimens demonstrated VL suppression (<50 copies/ml) at 48 weeks in 88% of those treated with dolutegravir and 85% for raltegravir combined with nucleoside reverse transcriptase inhibitors.³ Similarly, single-tablet regimens anchored by rilpivirine, elvitegravir, and efavirenz achieved virologic suppression in 90, 88, and 84% of individuals, respectively, in recent clinical trials.^18,19 The rates of VL suppression observed in our USAF active duty population were comparable to recent clinical trials. In addition, the higher proportion of VL suppression observed at one year during 2006–2011 (93.2%) compared with 2000–2005 (78.6%) coincided with FDA approval of the first single-tablet regimen (efavirenz/emtricitabine/tenofovir) in 2006, which was used in nearly half of individuals in our cohort initiating ART from 2006 to 2011. Since there were no changes in the mandated clinical visit structure or other major administrative changes in the USAF HIV programme during the study period, it is likely that improved potency, efficacy, tolerability, and convenience of contemporary antiretrovirals significantly contributed to the higher rate of VL suppression observed in those initiating ART during or after 2006.

Patient characteristics often play a considerable role in predicting HIV treatment outcomes. One study identified substance and alcohol abuse as significant risk factors in the delay of ART initiation, and noted African American race, being uninsured, mental health disorders, substance abuse and higher CD4 count as characteristics associated with worse retention in care.²⁰ Intravenous drug use is exceedingly low (<1%) in the USAF population due to the periodic drug screening programme in the military.²¹ The low rate of substance abuse coupled with free, comprehensive health care coverage and mandated clinic visits may mitigate some of these factors that can contribute to suboptimal treatment outcomes in other settings. Military members may be more disciplined than other populations due to the structured atmosphere of military life. It is also possible that USAF members may be more adherent to ART, notwithstanding the potential rigors of serving on active duty. Future studies are warranted to evaluate the impact of military service on HIV outcomes, including medication adherence and other characteristics unique to the military, such as maintaining physical fitness standards.

A previous study in the US Military HIV Natural History Study (NHS) found that African Americans had lower odds of achieving VL suppression on ART, but our current study did not observe differing proportions of VL suppression by race/ethnicity.²² Although a small component (<10%) of our active duty USAF population was included in the prior NHS study, the overall NHS cohort population included members from other military branches with differing HIV programme structures, while the USAF is the only US military service that utilises a single-centre model of HIV care. A significant portion of the active NHS cohort is composed of non-active duty dependents and retirees, who are not subject to active duty regulations, and a prior NHS study reported that 25% of participants were non-active duty at the time of ART initiation.²³ Primary HIV care for non-active-duty participants may be conducted at non-NHS sites and clinical practice patterns may not be uniform in other settings. Some of these differing characteristics between the USAF and NHS may have accounted for differences in VL suppression, as the NHS previously reported that 81% of cohort members achieved VL suppression (<400 copies/ml) at one year, which differs from 88% VL suppression observed in the USAF population in our current study using more stringent VL criteria (<50 copies/ml).²³

In support of the validity and comparability of our findings to results reported in other HIV-infected populations, the timing and criteria for ART initiation during the 12-year study period mirrored trends in clinical practice and published treatment guidelines. For example, ART initiation was generally delayed for an average of two years in the early 2000s when treatment guidelines were primarily based on CD4 count thresholds, which is in contrast to the rapid initiation of ART observed for those diagnosed in 2010–2011 when guidelines favoured earlier therapy with less emphasis on CD4 counts. Similarly, the median CD4 count at time of ART initiation was 355 cells/µl during the study period; however, a significant trend for starting ART at higher CD4 counts was observed between 2006 and 2011 with a median CD4 count >400 cells/µl for those initiating ART in 2010–2011. CD4 gains while taking ART were similar with a median increase of 224 and 248 cells/µl in the early and later treatment periods, respectively. Although the current study was not sufficiently powered to study potential immunologic benefits based on timing of ART initiation, earlier treatment has been shown to improve outcomes in other studies including CD4 count recovery.^24–26

There are several potential limitations to this retrospective study. The decision to initiate ART and choice of regimen were not randomised and were made at the discretion of the individual physicians and patients; however, treatment decisions were in accordance with published guidelines during the study period. Although patients electing to separate from military service either before or within six months of initiating ART were not included in this study, the aim of this study was to evaluate USAF patients in the context of ongoing evaluation and treatment in the single-centre model for HIV care in the USAF. For the small proportion of patients that did not achieve or maintain VL suppression, the reasons for failed suppression, including adherence data, were not uniformly captured.

In conclusion, this study demonstrates the positive impact of a comprehensive clinical HIV programme that minimises traditional barriers to HIV care, including universal HIV screening, early HIV diagnosis, and rapid linkage and engagement in care at no cost to patients. Among those initiating ART during 2006–2011, 93% were suppressed 12 months later, consistent with results from recent randomised clinical trials. Although many challenges and obstacles exist along the continuum of HIV care, the success of this real-world programme reinforces the benefits of continuity of care at a single site with scheduled visits and provision of free access, treatment and medications in an era when treatment guidelines recommend universal ART use for HIV-infected patients.

Footnotes

Disclaimer

The content of this publication is the sole responsibility of the authors and does not necessarily reflect the views or policies of the Department of Defense or the Departments of the Army, Navy or Air Force.

Acknowledgments

The authors would like to thank John T. Brooks for critical review of the manuscript. Part of this study’s data was presented at ID Week 2013, San Francisco, CA.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

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