In the world of HIV care, there are few sets of documents more widely respected and universally used than the clinical practice guidelines issued by the U.S. Department of Health and Human Services (HHS).
As the number of HIV treatment options has burgeoned and patient management has democratized well beyond HIV specialists into fields such as primary and family care, the need has only grown for a single, authoritative source of up-to-date clinical guidance. The family of documents referred to colloquially as the HHS guidelines has filled that pivotal need.
HHS maintains more than a dozen HIV medical practice guideline documents, but five sets of guidelines in particular comprise the core of clinical HIV treatment and management wisdom in the U.S.:
HIV treatment guidelines for adults and adolescents (updated 7/10/19)
Opportunistic infection prevention and treatment guidelines for HIV-positive adults and adolescents (updated 5/26/20)
Perinatal HIV prevention guidelines (updated 12/29/20)
Pediatric HIV treatment guidelines (updated 4/8/21)
Pediatric opportunistic infection prevention and treatment guidelines (updated 8/29/19)
Here's a rundown of the most recent adjustments made to each of these critically important reference materials.
HIV Treatment Guidelines for Adults and Adolescents
The U.S. HHS treatment guidelines are authored and revised regularly by a rotating panel of dozens of practicing HIV clinicians, HIV researchers, HHS officials, HIV community members, and expert consultants. They represent the "gold standard" of our accumulated knowledge regarding the optimal approaches to antiretroviral therapy within the U.S.
The guidelines were updated twice in 2019. The most recent update featured adjustments in several areas, including:
Recommended first-line regimens. Dolutegravir/lamivudine (sold as the fixed-dose drug Dovato), which was approved in April 2019, was added to the list of recommended initial regimens -- albeit with caveats that the regimen should not be prescribed in cases where the patient's viral load is above 500,000 copies/mL, they have active hepatitis B infection (or their hepatitis B status is unknown), or their genotypic testing results for reverse transcriptase are unknown. In addition, bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) has been added as a treatment option in acutely or recently infected people for whom genotypic drug resistance testing has not yet been completed.
Easing of pregnancy warnings regarding dolutegravir. The more liberal approach to dolutegravir (Tivicay) comes in the wake of new research suggesting that earlier concerns regarding the relationship between birth defects (specifically, neural tube defects) and dolutegravir use were overblown. Current data don't exonerate dolutegravir, but they do place the relative risk of defects within a range low enough to warrant a more nuanced conversation about the drug's benefits and risks for women who might conceive.
Embrace of treatment as prevention. The guidelines were revised to more aggressively recommend immediate initiation of antiretroviral therapy following an HIV diagnosis, explicitly tying early and effective treatment to the elimination of sexual HIV transmission risk. The guidelines use the term "treatment as prevention (TasP)" to describe the strategy, but it is also commonly referred to as U=U, or "undetectable equals untransmittable."
Greater sensitivity to HIV treatment costs. Additional text has been added to walk providers through the complexities of HIV medication pricing in the U.S., including the differences between public and private health insurance options, as well as the potential impacts of cost-containment measures on patients' out-of-pocket medication costs.
Management of older patients. An updated section on HIV-positive adults over the age of 50 seeks to increase provider awareness of their patients' mental health needs, risk for neurocognitive issues, and the rising concerns of comorbidities, polypharmacy, and drug interactions among this patient population.
Prior to the Dec. 18 update, an update on July 10, 2019 featured the following changes:
Gender-affirming care. The guidelines were updated to explicitly call attention to the need for services to improve the continuum of care for transgender and nonbinary patients, including greater awareness of the interplay between HIV, antiretrovirals, and gender-affirming hormonal therapy.
Substance use. Information has been added to the guidelines regarding the provision of HIV care among people with a substance use disorder, with a particular focus on the relationship between HIV and alcohol; tobacco; benzodiazepines; cannabinoids; stimulants such as cocaine, methamphetamines, and other party drugs; and opioids.
HIV-2. The guidelines now recommend more aggressive treatment of HIV-2 than had previously been suggested, and they also recommend the use of integrase inhibitor-based therapy in an initial antiretroviral regimen.
Opportunistic Infection Prevention and Treatment Guidelines for HIV-Positive Adults and Adolescents
Opportunistic infection (OI) management remains a pivotal component of HIV patient care in the U.S., even in an era replete with highly effective and tolerable antiretroviral treatment options. The HHS OI guidelines are crafted by a panel of dozens of clinical and research experts, divided into groups by infection-specific expertise.
The OI guidelines document itself is divided into more than two dozen sections, each focusing on a discrete infection. As a result, the guidelines tend to be updated frequently, as each individual panel group completes a review of the recommendations regarding its particular section.
Since April 2019, the OI guidelines have been updated a dozen times. From most to least recent, here is a brief rundown of those revisions:
Candidiasis. On May 26, 2020, this section received a thorough update to its treatment and pregnancy information, including a warning against the use of fluconazole in the first trimester of pregnancy due to a potential risk for spontaneous abortion.
Herpes simplex virus. On May 26, 2020, updates were posted throughout this section, including new and additional information regarding HSV epidemiology, etiology, testing, prevention, and treatment.
Data on OI drugs in pregnancy. On Feb. 11, 2020, a table summarizing the safety during pregnancy of more than a hundred different OI drugs was updated to include several new hepatitis C treatment regimens (OK to use "if the benefit is felt to outweigh the potential risks"), the antifungal isavuconazole ("not recommended"), and the tuberculosis drug rifapentine ("use of alternate drugs" recommended).
Talaromycosis. On Nov. 21, 2019, this section (which was renamed from Pencilliosis earlier in 2019) received numerous changes, including adjustments to the recommendations for primary prophylaxis, induction therapy, consolidation therapy, and maintenance therapy.
Drug information. On Oct. 22, 2019, three general drug information tables were revised: one on drug-drug interactions, one on adverse drug reactions, and one on dosing in the setting of renal insufficiency.
Community-acquired pneumonia. On Oct. 10, 2019, this section (which had previously been titled "Bacterial Respiratory Disease") was overhauled, with substantive changes to guidance on risk factors, testing, pathogenesis, and treatment.
Mycobacterium tuberculosis. On Sept. 27, 2019, this section was updated significantly to reflect recent research findings on a range of issues related to tuberculosis treatment and patient management.
Histoplasmosis. On Sept. 13, 2019, this section was revised to include updated guidance regarding prophylaxis cessation, treatment intolerance, and diagnostics.
Varicella-zoster virus. On Sept. 5, 2019, this section received a significant revision, including the addition of recommendations regarding the use of recombinant zoster vaccine (Shingrix) and zoster vaccine live (Zostavax) to prevent herpes zoster in older people living with HIV.
Immunization scheduling. On Aug. 7, 2019, the guidelines were updated to reflect new recommendations from the Advisory Committee on Immunization Practices -- but the panel noted that further updates would soon follow that include information regarding newer vaccines.
Cryptosporidiosis. On July 16, 2019, updated information was added to this section regarding cryptosporidiosis risk, the importance of food and water safety precautions, the efficacy of multiplex molecular testing, and the relative efficacy of therapeutic agents among people living with HIV.
Microsporidiosis. On June 14, 2019, this section was revised with a range of updated information regarding microsporidia epidemiology, pathogenesis, and treatment.
Terminology and organization. On May 15, 2019, the full document was retitled from "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents" to "Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV," reflecting the growing use of destigmatizing people-first language within the HIV clinical realm. A number of sections within the guidelines were also renamed or re-ordered for greater accuracy and ease of use.
In December 2020, HHS guidelines regarding the prevention of mother-to-child HIV transmission received their first major refresh in two years. The guidelines are updated by a panel of over two dozen experienced clinicians and researchers from across the U.S., including individuals at universities, in private practice, and in the federal government. They are aimed at further reducing the U.S.’s extremely low perinatal HIV transmission rate while avoiding toxicities and adverse outcomes.
Two updates to the guidelines were posted in December: One on Dec. 15 and another on Dec. 29. The Dec. 15 update focused specifically on revised antiretroviral recommendations, most notably:
Dolutegravir’s addition as a preferred antiretroviral both for women who are pregnant (at any stage) or trying to conceive, in the wake of a growing body of research putting to rest prior concerns regarding the potential neural tube defects.
The addition of tenofovir alafenamide (TAF) as an alternate antiretroviral.
The downgrade of lopinavir/ritonavir (LPV/r, Kaletra) from an alternative antiretroviral to one that is generally not recommended.
The Dec. 29 update constituted a more expansive revision to many sections of the guidelines. Among the highlights:
A new section devoted to the use of pre-exposure prophylaxis (PrEP) before, during, and after pregnancy. In short: It’s worth offering tenofovir disoproxil fumarate/emtricitabine (TDF/FTC, Truvada) in nearly any scenario.
Adjustments throughout the document to be more properly inclusive of, and encourage greater provider sensitivity to, transgender and non-binary patients.
A strong recommendation that, in pregnant individuals who are coinfected with HIV and hepatitis C (HCV), HCV viral load be quantified after delivery and direct-acting antiviral treatment initiation be considered if spontaneous HCV clearance has not occurred.
The HHS guidelines for the treatment of children living with HIV in the U.S. have been updated several times since mid-2018. Taken together, these represent a substantial revision to the recommendations, which are reviewed by a panel of more than two dozen knowledgeable HIV clinicians and researchers located throughout the country.
The most recent update features:
A new discussion regarding telehealth and telemedicine in the context of pediatric HIV care.
Added guidance for determining whether particular issues require clinical attention in person vs. via telemedicine.
An expansion of the “preferred” regimen designation for dolutegravir (Tivicay) plus two NRTIs, which is now recommended for anyone age 4 weeks or older provided they weigh at least 3 kg. (The prior recommendation was restricted to people at least 3 years old weighing a minimum of 25 kg.)
The addition of bitegravir, as part of bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy), in people at least 6 years old and weighing a minimum of 25 kg.
A note that the NRTI backbone of abacavir (Ziagen) alongside either emtricitabine (Emtriva) or lamivudine (Epivir) is classified as “preferred” for children at least one month old, despite the FDA approval for the drug specifying an age of least three months.
The downgrade of raltegravir (Isentress)-based regimens from “preferred” to “alternative” because it is not a once-daily medication and is more prone to emergent resistance compared to other preferred integrase inhibitors.
A note that zidovudine can be considered an “alternative” NRTI in children at least one month old.
A number of updates to sections regarding perinatal exposure to HIV, including revised guidance on HIV testing for pregnant women, optimal approaches to managing perinatal HIV exposure, and the diagnosis of mother-to-child HIV transmission.
The prior update, on April 14, 2020, was headlined by an expansion of the test-and-treat approach (i.e., begin HIV treatment as soon as possible after diagnosis) to incorporate all children regardless of age, not just children under the age of 1. It also included a number of updates to reflect recent FDA approvals, efficacy data, and safety data regarding antiretroviral use in children—including new guidance regarding the use of atazanavir, cobicistat, darunavir, lopinavir/ritonavir, and raltegravir.
These adjustments reflect only the latest of a series of changes over the past few years to the lists of preferred and alternative regimens, as a range of new data have become available regarding the safety and efficacy of newer antiretrovirals, particularly integrase inhibitors such as dolutegravir and raltegravir.
Pediatric Opportunistic Infection Prevention and Treatment Guidelines
After being largely left untouched for much of this decade, HHS recommendations regarding the prevention and treatment of opportunistic infections in children have seen a flurry of updates since mid-2018, as the panel (of dozens of experts) shifted to a more modular approach that allowed them to update smaller subsections as needed, rather than complete a comprehensive review of the entire document only once every few years.
That said, most of the changes to these guidelines in 2019 have been relatively minor, focusing on updated information regarding epidemiology, immunizations, pathogenesis, and testing methodology. The specific sections receiving these updates are:
cryptosporidiosis (on Aug. 29, 2019)
cystoisosporiasis, formerly known as isosporiasis (on Feb. 8, 2019)
giardiasis (on Aug. 22, 2019)
Mycobacterium avium complex disease (on Jan. 8, 2019)