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DHHS Guidelines Recommend ART for All HIV+, New Info on Older Patients and HIV/HCV Coinfection

The U.S. Department of Health and Human Services (DHHS) this week released an updated version of its Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. The DHHS panel now recommends that antiretroviral therapy (ART) should be offered to everyone diagnosed with HIV. Other highlights include new sections on aging with HIV and drug costs, more information on antiretroviral treatment as prevention, and recommendations for use of new hepatitis C protease inhibitors in HIV/HCV coinfected people.

[Editor's Note: The DHHS guidelines are written by a panel of clinicians, researchers, community activists, and government representatives. Paul Dalton is a community member of the panel. This article is written as an individual, not as a representative (official or otherwise) of the panel.]

The updated guidelines, released March 27, 2012, include 2 new sections -- HIV and aging, and drug costs -- as well as updates to several sections including "Initiating Antiretroviral Therapy in Treatment-Naive Patients," "HIV-Infected Women," "Prevention of Secondary Transmission," "HIV/Hepatitis C Coinfection," and "Mycobacterium Tuberculosis Disease with HIV Coinfection."

HIV and the Older Patient

Perhaps the most notable change in this update is a new section entitled "HIV and the Older Patient." This discussion arose from growing community and scientific attention to the interplay between HIV and aging. This section was first proposed at a meeting of community advocates and researchers in Baltimore in 2011.

The guidance covers HIV testing, prevention of secondary transmission, initiation of antiretroviral therapy, co-morbidities, drug interaction, and discontinuation of antiretroviral drugs.

From the Guidelines (ratings in parentheses indicate the strength of the evidence for the recommendation):

Key Considerations When Caring for Older HIV-Infected Patients

• Antiretroviral therapy (ART) is recommended in patients > 50 years of age, regardless of CD4 cell count (BIII), because the risk of non-AIDS related complications may increase and the immunologic response to ART may be reduced in older HIV-infected patients.
• ART-associated adverse events may occur more frequently in older HIV-infected adults than in younger HIV-infected individuals. Therefore, the bone, kidney, metabolic, cardiovascular, and liver health of older HIV-infected adults should be monitored closely.
• The increased risk of drug-drug interactions between antiretroviral (ARV) drugs and other medications commonly used in older HIV-infected patients should be assessed regularly, especially when starting or switching ART and concomitant medications.
• HIV experts and primary care providers should work together to optimize the medical care of older HIV-infected patients with complex comorbidities.
• Counseling to prevent secondary transmission of HIV remains an important aspect of the care of the older HIV-infected patient.

The section touches on one of the most widely discussed aspects of HIV and aging -- whether HIV disease or its treatment leads to an accelerated aging process. While the causes are still being explored, most experts in the field believe that people with HIV appear to be aging faster. Conditions associated with aging, such as heart disease, cognitive decline, and bone weakening, develop somewhat earlier among people living with HIV, including those on effective ART.

Aging complicates antiretroviral treatment itself. The guidelines recommend that all people over 50 years old begin ART, regardless of CD4 count. Blunted CD4 recovery, increased complexity of drug-drug interactions, and the co-management of aging-related diseases all factor into when and what to start.

Drug Costs

The other new section is an appendix on drug costs, which simply lists the Average Wholesale Price (AWP) of each approved HIV drug and fixed-dose combination pill.

When to Start ART

In the section on "Initiating Antiretroviral Therapy in Treatment-Naive Patients," the major change is a recommendation for treatment of all people with HIV, "primarily based on increasing evidence showing the harmful impact of ongoing HIV replication on AIDS and non-AIDS disease progression." In addition the updated recommendations "reflect emerging data showing the benefit of effective ART in preventing secondary transmission of HIV."

From the Guidelines:

• ART is recommended for all HIV-infected individuals. The strength of this recommendation varies on the basis of pretreatment CD4 cell count:

o      CD4 count < 350 cells/mm³

o      CD4 count 350 to 500 cells/mm³

o      CD4 count >500 cells/mm³.

• Regardless of CD4 count, initiation of ART is strongly recommended for individuals with the following conditions:

o      Pregnancy (see perinatal guidelines for more detailed discussion);

o      History of an AIDS-defining illness

o      HIV-associated nephropathy (HIVAN)

o      HIV/hepatitis B virus (HBV) coinfection

• Effective ART also has been shown to prevent transmission of HIV from an infected individual to a sexual partner. Therefore, ART should be offered to patients who are at risk of transmitting HIV to sexual partners [heterosexuals] or  [other transmission risk groups]).
• Patients starting ART should be willing and able to commit to treatment and should understand the benefits and risks of therapy and the importance of adherence. Patients may choose to postpone therapy, and providers, on a case-by-case basis, may elect to defer therapy on the basis of clinical and/or psychosocial factors.

Women with HIV

This revised section includes further discussion on the use of hormonal contraception by HIV positive women, focusing on drug-drug interactions between oral contraceptives and antiretroviral drugs, as well as recent conflicting datashowing a possible association between hormonal contraceptive use and higher risk of acquisition or transmission of HIV.

HIV/HCV Coinfection


Updates to this section focus on the recently approved HCV protease inhibitors boceprevir (Incivek) and telaprevir (Victrelis), including known interactions between these drugs and antiretrovirals, and interim results from ongoing studiesof protease inhibitors plus pegylated interferon/ribavirin in HIV/HCV coinfected patients.

For patients not on ART or taking a regimen of raltegravir plus 2 NRTIs, the panel recommends either boceprevir or telaprevir. Due to uncertainty about interactions with boceprevir, the panel advises that people taking atazanavir (Reyataz) should use telaprevir at the standard 750 mg 3-times-daily dose, while those taking efavirenz (Sustiva) should up the dose to 1125 mg. The panel emphasizes that "These recommendations may be modified as new drug interaction and clinical trial information become available."

HIV and TB

The panel also updated their recommendations for the treatment of Mycobacterium tuberculosis(TB) in people living with HIV. The main changes have to do with the timing of initiation of ART after starting TB treatment:

• For patients with CD4 counts < 50 cells/mm³, ART should be initiated within 2 weeks of starting TB treatment (AI).
• For patients with CD4 counts > 50 cells/mm³ with clinical disease of major severity as indicated by clinical evaluation (including low Karnofsky score, low body mass index [BMI], low hemoglobin, low albumin, organ system dysfunction, or extent of disease), the Panel recommends initiation of ART within 2 to 4 weeks of starting TB treatment (BI for CD4 count 50-200 cells/mm³ and BIII for CD4 count > 200 cells/mm³).
• For other patients with CD4 counts > 50 cells/mm³, ART can be delayed beyond 2 to 4 weeks but should be initiated by 8 to 12 weeks of TB therapy (AI for CD4 count 50-500 cells/mm³; BIII for CD4 count > 500 cells/mm³).

Treatment as Prevention

The final major update was to the "Prevention of Secondary Transmission" section. Most importantly, there is a discussion about antiretroviral treatment as prevention. Citing the HTPN 052 study, the guidelines state that effective ART greatly reduces the risk of secondary HIV transmission. This protection is mitigated by the challenges of optimal antiretroviral adherence, along with some evidence that risk-taking behavior may increase when people believe they are on suppressive therapy.

From the Guidelines:

Consistent and effective use of ART resulting in a sustained reduction in viral load in conjunction with consistent condom usage, safer sex and drug use practices, and detection and treatment of [sexually transmitted diseases] are essential tools for prevention of sexual and blood-borne transmission of HIV. Given these important considerations, medical visits provide a vital opportunity to reinforce HIV prevention messages, discuss sex- and drug-related risk behaviors, diagnose and treat intercurrent [sexually transmitted diseases], review the importance of medication adherence, and foster open communication between provider and patient.

Other Changes

Minor updates were made to various other sections, including drug interaction tables, goals of treatment, "What to Start," "HIV and Illicit Drug Users," "Adherence to Antiretroviral Therapy," and "Adverse Effects of Antiretroviral Agents."

The Guidelines Panel is accepting feedback on the latest revisions to the adult and adolescent treatment guidelines, as well as the new format.Please send comments with the subject line "Adult and Adolescent Guidelines Comments" to JLIB_HTML_CLOAKING by April 10, 2012.

3/30/12

Reference

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. March 27, 2012.