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Physicians practicing in rapidly evolving areas of medical care, and policy makers charged with supporting that care, both benefit from informed guidance regarding testing, new treatments, and innovations in disease prevention. Approaches to HIV care and prevention have both been improved by access to such guidance. Clinicians who care for patients with HIV follow newly published or presented data, the opinion of respected experts, and guidelines created by governmental or private organizations. Guideline groups have various “rules” regarding the inclusion of expert opinion, which publications are allowed, and how critically those research reports are evaluated. Clinicians expect guidelines to rapidly incorporate new data, and many immediately use guidelines to improve care for their patients.
Policy makers also rely on published guidance. Their decisions typically affect large populations and are used to decide which drugs, tests, or strategies will be provided by public and private sources. Because implementing policy takes considerable time, requiring consensus-building among disparate groups and disease states competing for resources, policy guidelines are often more conservative and restrictive regarding the strength of evidence and the needed quality of the supporting data. Policy guidelines may be limited to published work or to results of randomized trials and may more favorably weigh large sample sizes and expect freedom from several types of research design bias. Expert opinion in policy guidelines is largely discounted.
In HIV care and prevention, the nature and use of differing guidelines is quite evident. As an example, treatment guidelines, reflecting more expert opinion, have recommended initiation of antiretroviral therapy at much earlier disease stages, eventually including all infected persons regardless of CD4 cell counts.1 In contrast, policy guidelines took several years to reach that conclusion, which did not occur until the publication of a large randomized clinical trial.2 Clinicians who provided care for patients with HIV were divided; some favored treating earlier, whereas others reflected a more cautious stance and also chose to wait for those data. A more data-driven approach to medical decisions and the merging of treatment and policy guidance has been strongly endorsed by the move to what is commonly called evidence-based medicine. As clinicians are increasingly asked to account for the costs and outcomes of their care, this movement toward stricter evidence is clearly gaining momentum, despite frequent criticism by some physician experts who perceive that the process is unnecessarily slow.
The US Preventive Services Task Force (USPSTF), an independent, volunteer body (supported with governmental funds, but its recommendations are not influenced by government employees) is charged with developing evidence-based recommendations for primary care clinicians about clinical preventive services. Its scope is broad and aimed at effecting policy and improving care and prevention outcomes. Along with recommendations for many other diseases, the task force has, for years, made recommendations regarding HIV care and prevention. The USPSTF develops guidelines using methods that closely adhere to the recommendations of the National Academy of Medicine. When published, USPSTF guidelines make recommendations that are given a letter grade reflecting the data quality and strength of the recommendation; those with an “A” grade represent services that should be offered or provided because there is a “high certainty that the net benefit is substantial.”
In this issue of JAMA and published online, the USPSTF presents 2 important Recommendation Statements that focus on HIV, along with 3 commissioned evidence reviews.3-7 The 2 Recommendation Statements include 3 A-level recommendations. The guidelines address HIV screening in adults, adolescents, and pregnant women (updates of previous guidelines) and also include a new guideline on the use of antiretroviral drugs as preexposure prophylaxis (PrEP) for HIV prevention. The new guidelines show a maturation of evidence and policy in HIV medicine and a growing consensus affecting application, not only in the United States but worldwide. The issues raised in the guidelines and in the supporting evidence continue to reflect USPSTF methods and should reinforce current practices. Even though the new recommendations seem secure, continued research will almost certainly allow further refinements.
This guideline recommends HIV screening of individuals aged 15 to 65 years and of all pregnant women and gives both recommendations an A grade. In a sense, both recommendations, and the 2 supporting evidence reviews, are only partially about screening and are more directly about the treatment that follows for those found to have HIV infection based on that screening. The USPSTF addressed the overwhelming evidence that HIV treatment has benefits in preventing the morbidity and mortality of HIV infection and the (small) risk of harm to the treated individual from current antiretroviral medications. HIV treatment not only benefits the infected person but also is highly effective in preventing transmission to sexual partners and to the fetus and infant. The guideline cites high-quality evidence that early HIV treatment, including in persons with CD4 cell counts above 500/mm3, is of benefit, putting the USPSTF recommendations in direct support of World Health Organization guidelines and other guidelines that recommend treatment of all HIV-infected persons worldwide.8
In keeping with previous guidelines from the USPSTF, the latest Recommendation Statement on HIV screening does not address specific issues such as preferred drugs in HIV treatment or the still-evolving question of how soon treatment should be initiated after a diagnosis is made, with a growing trend to initiate treatment as soon as possible, even on the same day HIV infection is identified.9 Other important implementation issues unaddressed in the guideline include methods to optimize entry into care after diagnosis, means to achieve full viral suppression, or ways to retain in care persons being treated for long-term benefit and prevention of further HIV transmission. Finding insufficient evidence, the guideline also makes no recommendation regarding the optimum interval for repeat HIV screening.
With regard to treating HIV during pregnancy, the guideline summarizes the remarkable efficacy of antiretroviral treatment during pregnancy supported in earlier guidelines from this group. In the United States, fewer than 75 HIV-infected infants were born in 2017,10 and in many low- and middle-income countries, perinatal transmission rates have also declined substantially—but challenges remain. Rates of HIV infection in newborns of HIV-infected mothers remain stubbornly high in some regions of the world because of lower implementation of treatment guidelines. In considering the possible risks of HIV treatment during pregnancy, the task force found some evidence of increases in preterm births but no linkage to birth defects among infants exposed to antiretroviral drugs in utero. This last issue highlights a limitation of the deliberative USPSTF method. Since the supporting evidence for the current recommendation statement was collected, a report from Botswana11 found a higher than expected incidence of neural tube defects among infants born to women whose HIV treatment at conception included a commonly prescribed integrase inhibitor, dolutegravir, with 4 neural tube defects occurring among 426 infants. That report has led to rapid changes in international treatment guidelines and is considered the most pressing question regarding treatment of pregnant women with HIV, yet it is not discussed in the USPSTF guideline. If data emerge that confirm or refute this observation, it will likely be included in future iterations of this recommendation, particularly because the USPSTF is very attentive to harms, more so than most deliberative bodies.
While the first USPSTF guideline on HIV screening was a modest update of its prior work, the preexposure prophylaxis (PrEP) guideline is new. The Recommendation Statement is extremely timely, given a national initiative to end the HIV epidemic,12 and the accompanying evidence report shows PrEP to be both safe and highly effective in preventing HIV acquisition. The USPSTF is, again, deliberate in making its recommendation; PrEP, with the pill combining tenofovir disoproxil fumarate and emtricitabine, was approved by the US Food and Drug Administration in 2012 and first recommended by the Centers for Disease Control and Prevention in 2014. Although uptake of this prevention strategy has been increasing in the United States, implementation challenges remain, driven in part by cost and access. Currently, less than 10% of individuals with an indication for PrEP are receiving this medication.13 The gap between indication and use is most pronounced among black and Latino men who have sex with men, despite a higher number of HIV diagnoses in these groups.13 The evidence developed by the task force in support of the new guideline, and the strong A recommendation, should serve to promote policies to expand PrEP access to those at risk, including men who have sex with men, women, and people who inject drugs.
The USPSTF Recommendation Statement on PrEP makes it clear that all clinicians must improve the assessment of HIV acquisition risk to identify all individuals for whom this prevention tool is appropriate, regardless of their demographic group and activity of risk. While acknowledging these concerns, many recommend reframing PrEP assessment as part of a larger strategy of supporting sexual health, moving away from a “risk” framework to encourage uptake.14 Furthermore, although not directly addressed in this task force report, current individual risk behavior assessments often underestimate the true risk, especially for priority populations such as black men who have sex with men, and so need further refinement.15
The task force Recommendation Statement also notes that PrEP, in some trials, has been completely effective in preventing HIV infection, but only if medication adherence is continuously high. Adherence support from clinical and nonclinical staff—the Achilles heel of PrEP success—is essential, but especially for youth and women among whom adherence has been low.16 Nonetheless, clinician concern that a candidate for PrEP might be less fully adherent should not be used to withhold this medication, as doing so may further add to the already existing disparity in HIV prevention in those at highest need. Modeling studies suggest that PrEP coverage, even with suboptimal adherence, is the most important factor to avert new HIV infections.17
The recommendations for PrEP, adding the full endorsement of the USPSTF, is of great importance and is needed to expand access and use of this effective HIV prevention strategy. While newer developments, including a new formulation of tenofovir or the use of injectable, long-acting drugs, were not included in this Recommendation Statement, these treatment strategies could be included in future iterations if supported by the high-quality evidence demanded by the task force.
The 2 new USPSTF Recommendation Statements underscore the remarkable progress in preventing and treating HIV infection. Together, the health gains in HIV treatment, the resulting reduction in transmission, and PrEP provide the necessary tools to end the HIV epidemic. Success in the next chapter in confronting this epidemic demands that these tools be widely accessible and used. The USPSTF Recommendation Statements should help make this happen.
Corresponding Author: Paul A. Volberding, MD, AIDS Research Institute, University of California San Francisco, 550 16th St, Third Floor, San Francisco, CA 94158 (Paul.Volberding@ucsf.edu).
Conflict of Interest Disclosures: Dr Volberding reported serving on a data and safety monitoring board for Merck. No other disclosures were reported.
Scott H, Volberding PA. HIV Screening and Preexposure Prophylaxis Guidelines: Following the Evidence. JAMA. 2019;321(22):2172–2174. doi:10.1001/jama.2019.2590
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