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New Guidance Addresses Expanded Antiretroviral Treatment, Perinatal ART, PrEP

On the occasion of the XIX International AIDS Conference (AIDS 2012) last week in Washington, DC, the International Antiviral Society-USA (IAS-USA) released new guidelines recommending that all people diagnosed with HIV should be offered antiretroviral therapy (ART).

The International Association of Physicians in AIDS Care (IAPAC) also released a consensus statement on treatment as prevention and pre-exposure prophylaxis (PrEP) at the conference, and this week the Department of Health and Human Services (DHHS) updated its perinatal antiretroviral guidelines.

IAS ART Guidelines

IAS-USA -- formerly known as the International AIDS Society-USA -- published its latest recommendations in the July 25, 2012, HIV theme issue of the Journal of the American Medical Association.

The new IAS-USA guidance matches the current DHHS adult and adolescent antiretroviral guidelines in recommending combination antiretroviral treatment for everyone with HIV regardless of CD4 T-cell count.

The revision is supported by a growing body of evidence showing that ongoing HIV replication is harmful and treatment is beneficial well before a person's CD4 count falls to 500 or 350 cells/mm³ (initiation thresholds in prior guidelines). There is also now compelling evidence that treatment prevents sexual transmission of HIV.

"When HIV is allowed to replicate uninhibited by ART, resultant immune activation and inflammation are associated not only with immune destruction and opportunistic infections but also increased rates of cardiovascular, renal, hepatic, and neurologic diseases; malignancies; and other serious non-AIDS diseases," the IAS-USA authors wrote. "Evidence from clinical trials, observational cohorts, and pathogenesis studies all point toward the health benefits of earlier ART."

The recommended first-line regimen for treatment-naive people remains 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus a third agent -- either the NNRTI efavirenz (Sustiva), the ritonavir-boosted protease inhibitors atazanavir (Reyataz) or darunavir (Prezista), or the integrase inhibitor raltegravir (Isentress).

The IAS-USA panel re-added abacavir/lamivudine (the drugs in Epzicom) as a preferred NRTI "backbone" option -- for people with a negative HLA-B*5701 test -- in addition to tenofovir/emtricitabine (the drugs in Truvada). Some studies have suggested that abacavir may be associated with increased risk of cardiovascular events, but data have not been consistent. Tenofovir has been linked to kidney problems and bone loss. The choice of NRTIs, therefore, should be informed by individual risk factors.

The single-tablet regimen Atripla contains efavirenz plus tenofovir/emtricitabine. The Complera combination pill, containing the NNRTI rilpivirine plus tenofovir/emtricitabine, is recommended as an alternative first-line regimen only for people with a baseline viral load < 100,000 copies/mL.

Looking ahead, the panel said the 4-in-1 Quad pill -- containing the integrase inhibitor elvitegravir, the novel boosting agent cobicistat, and tenofovir/emtricitabine -- will be an alternative if it receives FDA approval.

The new guidelines also include a discussion of Truvada for PrEP, which the FDA just approved on July 16.

IAPAC Consensus Statement

IAPAC released its new consensus statement on treatment as prevention (TasP) and PrEP at a July 26 press conference. The statement was developed by an international advisory committee that analyzed data presented and discussed at an IAPAC summit on "Controlling the HIV Epidemic with Antiretrovirals," held in London in June.

IAPAC announced its "full embrace" of TasP and PrEP, and called for "immediate integration of these interventions into the existing HIV armamentarium as a means of significantly impacting HIV incidence worldwide."

Speaking at the presser, IAPAC TasP/PrEP Advisory Committee members Kenneth Mayer, medical research director at the Fenway Institute in Boston, and Julio Montaner from the British Columbia Centre for Excellence in HIV/AIDS both stressed that PrEP is a "niche" intervention for carefully selected individuals at high risk for HIV acquisition, not a life-long prospect for all HIV negative people.

"The way forward needs to be met with very careful implementation science studies, so-called demonstration projects, around the world so that we know how best to roll out these interventions for key populations in different settings," Mayer said. "This will not be a one-size-fits-all scenario."

Perinatal ART

Finally, on July 31, DHHS released a revision of its Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Healthand Interventions to Reduce Perinatal HIV Transmission in the United States.

These guidelines, too, reflect the shift in emphasis toward antiretroviral treatment as prevention and PrEP, recommending ART and PrEP for serodiscordant heterosexual couples who wish to conceive.

In addition, various antiretroviral agents have been reclassified in the categories of Preferred Agents, Alternative Agents, or Use in Special Circumstances. Atazanavir moved onto the recommended list while darunavir and raltegravir moved onto the alternative list thanks to additional data.

The new guidelines include more discussion of trimester timing of ART initiation in previously untreated pregnant women, as well as continuation of efavirenz by HIV positive women who seek prenatal care during the first trimester. Due to its association with neural tube birth defects, pregnant women have traditionally been discouraged from using efavirenz. But since the risk is limited to the first 5-6 weeks of gestation -- when most women do not yet know they are pregnant -- the panel now states that "efavirenz can be continued in pregnant women receiving an efavirenz-based regimen who present for antenatal care in the first trimester, provided the regimen produces virologic suppression."

The guidelines now state that intravenous zidovudine (AZT; Retrovir) during labor is only needed if women have detectable viral load > 400 copies/mL near the time of delivery. Use of raltegravir in late pregnancy to decrease viral load is discussed, but not endorsed.

The panel also updatedrecommendations for antiretroviral prophylaxis for newborns to prevent mother-to-child HIV transmission and advised healthcare providers about safer infant feeding options.

8/3/12

References

MA Thompson, JA Aberg, JF Hoy, et al. Antiretroviral Treatment of Adult HIV Infection 2012 Recommendations of the International Antiviral Society–USA Panel. Journal of the American Medical Association 308(4):387-402. July 25, 2012.

IAPAC. Controlling the HIV Epidemic with Antiretrovirals. Consensus statement. July 26, 2012.

HHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. July 31, 2012.