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Virologic Impact of Starting ART Above 500 CD4s at San Francisco General Hospital
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19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seattle
Mark Mascolini
When San Francisco General Hospital (SFGH) adopted a policy of offering antiretroviral therapy (ART) to everyone diagnosed with HIV regardless of CD4 count, the proportion of people who rapidly suppressed HIV RNA jumped from 1 in 10 to 1 in 2, a result with profound implications for public health as well as individual care.
Research results indicate that continuous viral suppression lowers the risk of serious non-AIDS illness and suggest that starting antiretroviral therapy at a CD4 count above 500 may improve survival, noted SFGH researchers. In December 2007, for the first time the US Department of Health and Human Services (DHHS) antiretroviral guidelines for adults and adolescents considered starting ART at a count above 500 "optional" instead of "not recommended." DHHS guidelines now set 500 CD4s as the antiretroviral start threshold and note that half of the guideline panel believes ART should start at any CD4 count.
In February 2010 SFGH, a public health hospital, adopted a "universal ART" approach that recommends treatment for everyone diagnosed with HIV regardless of CD4 count. The San Francisco Department of Health endorses that position. Elvin Geng and SFGH researchers planned this study to assess the impact of DHHS and SFGH recommendations on overall viral load distribution in the hospital population.
The study involved HIV-positive adults who had at least one primary care visit at the SFGH HIV clinic from 2001 through 2011 and went at least 90 days before starting ART. Geng and colleagues collected clinical, laboratory, and sociodemographic data on all these patients and calculated the distribution of average within-patient viral load in each year from 2001 to 2011, stratified by CD4 count at entry. They used survival analysis to estimate viral suppression--defined as a load below 500 copies--stratified by CD4 count at clinic entry. The investigators paid particular attention to viral suppression rates in reference to three dates:
-- April 4, 2005: the midway point during a period of stable ART initiation recommendations
-- December 1, 2007: first DHHS guidelines favoring starting ART above 350 CD4s
-- February 1, 2010: date SFGH adopted the "universal ART" approach
During the study period 2546 HIV-positive peopleentered the SFGH clinic not taking ART. The group had a median age of 38 years (interquartile range [IQR] 32 to 45), 88% were men, 52% white, 24% black, 19% Hispanic, and 6% Asian. While 46% of the study group got infected during gay sex, 22% became infected while injecting drugs and 14% during heterosexual sex. Median CD4 count at entry stood at 352 (IQR 152 to 512) and median viral load at 35,679 (IQR 10,621 to 111,700).
The proportion of people with a viral load below 350 copies rose steadily from 2001 through 2011 for those with CD4 counts below 500 at clinic entry. For example, among people who started care at the clinic with 200 to 350 CD4s, the proportion with a viral load under 500 climbed from about 10% in 2001 to more than 60% in 2011. Among people who entered the SFGH clinic with more than 500 CD4s, the proportion with a viral load under 500 stayed below 20% from 2001 through 2006, then rose gradually to reach about 40% by 2010; in the next year, that proportion jumped to more than 50%.
Geng and colleagues summarized these viral suppression changes this way:
1. The proportion of people with a clinic-entry CD4 count under 350 who rapidly suppress viral load below 500 copies increased steadily throughout the past decade.
2. In patients with an entry count between 351 and 500, the suppression rate began to climb before the clinic instituted its "universal ART" policy in February 2010 and rose markedly after the policy was in place.
3. Among people with an entry CD4 count above 500, the DHHS guideline change in 2007 had no perceptible effect on HIV RNA outcomes. But the 2010 change in clinic policy dramatically improved the proportion of people who reached a viral load below 500--from 1 in 10 to 1 in 2.
Average viral load fell throughout the study period, most steeply for people who entered the clinic counting fewer than 200 CD4s (from over 100,000 copies to about 40,000). Among people in the other clinic-entry CD4 brackets (200 to 350, 351 to 500, and over 500), average viral load dropped from between 40,000 and 60,000 in 2001 to about 20,000 in 2011.
Compared with people who entered the clinic before April 2005, those who entered between April 2005 and July 2007 did not have a significantly better chance of reaching a viral load below 500 copies 6 months after entry, but those who entered the clinic between July 2007 and February 2010 or after February 2010 often had a better chance of suppression, at the following risk ratios (RR) (and 95% confidence intervals):
Chance of reaching a viral load below 500 within 6 months of clinic entry, compared with clinic entry before April 2005 (n = 2546)
Entry CD4 below 200:
-- April 2005 to July 2007: Not significant
-- July 2007 to February 2010: RR 1.49 (1.06 to 2.08)
-- After February 2010: RR 1.64 (1.06 to 2.55)
Entry CD4 200 to 350:
-- April 2005 to July 2007: Not significant
-- July 2007 to February 2010: RR 1.79 (1.01 to 3.17)
-- After February 2010: Not significant
Entry CD4 351 to 500:
-- April 2005 to July 2007: Not significant
-- July 2007 to February 2010: RR 2.62 (0.96 to 7.10, nonsignificant trend)
-- After February 2010: RR 2.38 (1.25 to 4.55)
Entry CD4 above 500:
-- April 2005 to July 2007: Not significant
-- July 2007 to February 2010: Not significant
-- After February 2010: RR 5.28 (2.17 to 12.82)
Time to viral load rebound after a first viral load below 500 did not differ significantly across the four starting CD4 brackets (P = 0.26).
The SFGH team concluded that, "in a public health setting with patients with multiple comorbidities, treatment of patients who enter with CD4 levels above 500 is acceptable and feasible." If efforts at earlier HIV diagnosis succeed, they observed, a growing proportion of people will be diagnosed with a CD4 count above 500. Their clinic experience "suggests that local public health leadership can influence clinical practice and outcomes through 'practice policies'" that could benefit individual and public health.
A separate modeling study calculated that expanding ART to all HIV-positive adults in care in San Francisco would cut the new infection rate 59% among men who have sex with men (MSM) in 5 years [2]. Adding annual HIV testing for MSM to universal ART would slice the new infection rate by 76%.
References
1. Geng E, Kahn J, Christopoulos K, et al. The effect of a municipal "universal ART" recommendation on HIV RNA levels in patients entering care with a CD4 count greater than 500 cells/muL. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012. Seattle. Abstract 671.
2. Charlebois ED, Das M, Porco TC, Havlir DV. The effect of expanded antiretroviral treatment strategies on the HIV epidemic among men who have sex with men in San Francisco. Clin Infect Dis. 2011;52:1046-1049.
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