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CROI 2012: San Francisco Early HIV Treatment Policy Linked to Lower Viral Load, Higher CD4 Count

San Francisco's policy of offering antiretroviral therapy (ART) to everyone who tests positive for HIV regardless of CD4 T-cell count has resulted in higher average CD4 counts at the time of treatment initiation and faster suppression of HIV viral load, researchers reported at the at the 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012) this month in Seattle.

In early 2010San Francisco General Hospital (SFGH) and other facilities run by the San Francisco Department of Public Health (SFDPH) adopted a controversial policy of providing ART to all patients diagnosed with HIV, rather than waiting until CD4 counts fell into the 350-500 cells/mm³ range specified in the U.S. DHHS treatment guidelines in effect at the time. Updated guidelines released this week now also recommend universal treatment for everyone diagnosed with HIV.

Those arguing in favor of expanded treatment pointed to a growing body of evidence showing that early ART can help prevent non-AIDS complications that occur well before a person's CD4 cell count falls into the danger zone. HIV has detrimental effects throughout the body -- including chronic immune activation and inflammation -- starting from the earliest stages of infection.

Opponents of universal early treatment expressed concerns about long-term drug toxicities, emergence of drug-resistant virus, the difficulty of life-long adherence, and increased cost.

At CROI, Elvin Geng and colleagues from the University of California at San Francisco (UCSF) presented findings from a study of clinical practice and patient outcomes since the new policy went into effect.

The analysis included untreated adult patients (defined as at least 90 days without ART) who made at least 1 primary care visit to SFGH's Ward 86 HIV/AIDS Clinic between 2000 and 2011.

The researchers looked at changes over time in the likelihood of HIV RNA suppression below 500 copies/mL among patients who started care with different CD4 counts, focused on some key dates:

• April 4, 2005: publication of U.S. national guidelines recommending ART initiation only at CD4 levels < 200 cells/mm³;
• December 1, 2007: first U.S. guidelines recommending ART initiation at CD4 counts > 350 cells/mm³;
• February 1, 2010: introduction of San Francisco's universal ART approach.

Results

• Over the course of the decade, 5963 people were treated at the clinic, including 2546 previously untreated patients entering care.
• Within the untreated group, most (88%) were men, more than half (52%) were white, 24% were black, the median age was 38 years, 46% were men who have sex with men (MSM), and 22% had history of injection drug use.
• In this group the median CD4 count at entry to care was 325 cells/mm³ and the median HIV RNA level was 35,679 copies/mL.
• Average viral load fell steadily over the decade, with the largest drop seen among people who started care with < 200 cells/mm³.
• Looking at the overall clinic population, the proportion who achieved viral load < 500 copies/mL within 6 months steadily rose, while the percentage with > 50,000 copies/mL steadily fell.
  • Among people with < 200 cells/mm³ at clinic entry: from about 20% in 2001 to nearly 60% in 2011;
  • Among people with 350-500 cells/mm³ at entry: from about 10% to more than 60%;
  • Among people with > 500 cells/mm³ at entry: from less than 10% to just over 50%;
• In a multivariate analysis adjusting for age, sex, and injection drug use, the likelihood of HIV suppression more than doubled after adoption of the new policy.

"Among patients who enter [the] clinic with lower CD4 levels (i.e., < 350 [cells/mm³]) the fraction who rapidly suppress [HIV] after clinic entry increased steadily throughout the decade," the researchers summarized.

"Among patients entering with a CD4 [count] > 500 [cells/mm³], changes in DHHS guidelines in 2007 had no perceptible effect on HIV RNA outcomes," they continued. "The local clinic policy, however, had a pronounced effect in patients who enter [the] clinic with a CD4 [count] > 500 [cells/mm³] where it led to a rise in the fraction who rapidly suppress HIV RNA from 1 in 10 to 1 in 2. Patients with CD4 levels > 500 [cells/mm³] at ART initiation did not rebound sooner than those patients who started with lower CD4 levels."

"In a public health setting with patients with multiple co-morbidities, treatment of patients who enter with CD4 levels > 500 [cells/mm³] is acceptable and feasible," they concluded. "Successful implementation of universal treatment has the potential to benefit the health of the individual and reduce new infections in San Francisco."

New Disparities

The new universal ART policy is not all good news, however, as it has the potential to exaggerate disparities between people who receive standard-of-care treatment and those who do not.

Hong-Ha Truongfrom UCSF and colleagues at the Gladstone Institute of Virology and Immunology and SFDPH looked at treatment trends among 3858 San Francisco residents age 13 and older who were diagnosed with HIV between 2004 and 2010.

Results

• Among people with CD4 counts > 500 cells/mm³ at diagnosis, the median CD4 count at the time of ART initiation increased from 384 cells/mm³ in 2004 to 623 cells/mm³ in 2010.
• The proportion of patients initiating ART with CD4 counts > 500 cells/mm³ increased from 31% in 2004 to 89% in 2010.
• Among people with CD4 counts > 350 cells/mm³ at diagnosis, the median level at ART initiation rose from 365 cells/mm³ in 2004 to 504 cells/mm³ in 2010.
• The proportion of people initiating ART with CD4 counts > 350 increased from 48% in 2004 to 92% in 2010.
• CD4 counts dropped by an average of 135 cells/mm³ between diagnosis and ART initiation in 2004, but only by 5 cells/mm³ in 2010.
• People who started ART with CD4 counts > 500 cells/mm³ were significantly more likely to be white, men who have sex with men (MSM), and diagnosed by private clinicians, and less likely to be poor.
• People starting ART at > 350 cells/mm³ were significantly more likely to be older, white, MSM, and diagnosed by private providers, and again less likely to be poor.

"Evidence of the benefits with initiating ART at CD4 [counts] > 350 [cells/mm³] and possibly > 500 [cells/mm³] exposes a new potential inequality for populations already disproportionately affected by HIV, including youth, African Americans, the poor, and those diagnosed at facilities other than private providers," the researchers concluded.

"Unless these gaps are closed through specific efforts for earlier diagnosis, care, and ART initiation, we may observe increasing health and survival disparities among persons living with HIV," they added. "Industrialized countries could witness increasing disparities for marginalized populations and the developing world could miss an opportunity to dramatically improve health and alter the course of the epidemic."

3/27/12

References

E Geng, J Kahn, K Christopoulos, 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/mL. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 671.

H-H Truong, L Hsu, W McFarland, and S Scheer. Dramatic Improvements in Early ART Initiation Reveal a New Disparity in Treatment. 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012). Seattle, WA. March 5-8, 2012. Abstract 139.