What’s New in HIV Therapy?

BY HIND ALROWAIS, MD, AMY K. FEEHAN, PHD, AND JULIA GARCIA-DIAZ, MD

In the United States, an estimated 1.2 million people are living with HIV infection and many remain undiagnosed.1 HIV testing is recommended at least once for individuals aged 13 to 64 years, including all pregnant women, and more frequently for high-risk individuals.2,3 Initiation of antiretroviral therapy (ART) at the time of diagnosis has been shown to suppress viral load and prevent HIV transmission, rapidly improving individual and public health outcomes.4,5 Delaying treatment in patients with AIDS-defining illness, acute HIV infection, or pregnant women is associated with increased risk for HIV transmission, morbidity, and mortality.6 However, there are some instances when delaying treatment is appropriate: if a patient is not ready to commit to starting medications or is experiencing certain opportunistic infections, such as cryptococcal infection or tuberculosis meningitis.7,8 People with nonmeningeal tuberculosis can initiate ART immediately,9 as well as those with many other opportunistic infections or malignancies.6

New therapies for HIV continue to be developed; a private–public partnership was announced to accelerate the development of broadly neutralizing antibodies that can block the virus from invading cells.10 The FDA has just designated an experimental long-acting injectable, cabotegravir, as a breakthrough therapy for pre-exposure prophylaxis (PrEP).11 Several studies including GEMINI-1 and -2 have shown that sometimes less is more; 2-drug regimens are noninferior to 3-drug regimens and often have fewer side effects. New treatment options are beginning to be used clinically for experienced patients—the CD4 attachment inhibitors fostemsavir (Rukobia, ViiV Healthcare) and ibalizumab-uiyk (Trogarzo, Thera technologies). This article will discuss recent advancements in treatment and changing ideas on how to manage HIV.

Seven classes of ART are FDA-approved for the treatment of HIV infection. They include the nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transfer inhibitors (INSTIs), a fusion inhibitor (FI), a CCR5 antagonist, and CD4 T lymphocyte (CD4) postattachment inhibitors. In addition, 2 drugs, ritonavir (RTV) and cobicistat (COBI), are used as pharmacokinetic (PK) enhancers to improve the PK profiles of PIs and the INSTI elvitegravir (EVG).6 Selected agents within these drug classes are summarized in Table 1. Additionally, islatravir (ISL) is the first in a new class of drugs called nucleoside reverse transcriptase translocation inhibitors (NRTTI), but this compound is still in phase 3 clinical trials.

Studies have repeatedly shown the benefits of initiating treatment as soon as possible after diagnosis,4,5 and official guidelines support rapid treatment initiation.3 (A table showingthe most up-to-date guidelines on initiating therapy is available with the online version at https://www.idse. net/Review-Articles/Article/12-20/Whats-New-inHIV-Therapy/61408.) Early initiation of treatment offers many benefits, including breaking the chain of transmission, lowering barriers to entry, establishing a pattern of treatment, and preparing the patient for a lifetime of care. Health care practitioners should select therapy that is the most potent while minimizing short- and long-term side effects, and reducing the chances of drug resistance. Initial therapy should include a 3-drug regimen with an integrase inhibitor as backbone (dolutegravir or bictegravir) and 2 NRTIs. Generally, abacavir is less desirable than tenofovir because it requires HLA B*5701 testing to avoid serious side effects and is associated with increased risk for cardiovascular disease. After initial treatment, there are many options for maintenance therapy.

2- Versus 3-Drug Regimens

Strategies that minimize burden increase patient adherence, and nowhere is this truer than in the case of single-tablet regimens (STRs) for 3-drug treatment. The first STR was approved in 2006, efavirenz-emtricitabine-tenofovir disoproxil (EFV/FTC/ TDF; Atripla, Gilead), but this EFV-based regimen is known to cause neurologic and neuropsychiatric side effects, including nightmares, depression, suicidal ideation, dizziness, and lack of concentration.12

The first 2-drug regimen was approved in 2017, dolutegravir-rilpivirine (DTG/RPV; Juluca, ViiV Healthcare), after SWORD-1/2 trials showed virologic suppression and a favorable safety profile. DTG/RPV is indicated as a replacement only in patients with levels of HIV-1 less than 50 copies/ mL for at least 6 months on their current HIV treatment.13 DTG with lamivudine (DTG/3TC; Dovato, ViiV Healthcare) was approved in 2019, and is recommended for initial treatment of naive patients with a viral load less than 500,000 copies/mL, without active hepatitis B infection, and a CD4 count more than 200 cells/mm3 .

There is growing interest in 2-drug regimens with DTG and 3TC. Two parallel, phase 3 randomized clinical trials, GEMINI-1 and GEMINI-2, showed the 2-drug regimen with DTG/3TC was noninferior to a 3-drug regimen with DTG plus TDF/FTC in terms of virologic efficacy. The primary end point was the proportion of participants with HIV-1 RNA plasma less than 50 copies/mL at week 48; a secondary end point included the proportion of participants with HIV-1 RNA plasma less than 50 copies/mL at week 144, which was recently presented at the HIV Glasgow 2020 Congress.14 A pooled analysis of the 2 studies showed that DTG/3TC demonstrated noninferiority, with 82% (584/716) of participants having HIV-1 RNA less than 50 copies/mL at week 144, compared with 84% (599/717) receiving a 3-drug regimen of DTG plus TDF/FTC (adjusted difference, –1.8%; 95% CI, –5.8% to 2.1%). Cholesterol measurements at 144 weeks were better in the 3-drug regimen, but renal and bone measurements were better in the 2-drug regimen. Inclusion criteria were limited to patients with a viral load less than 500,000 copies/mL and without active hepatitis B infection or any pre-existing major viral resistance mutations. Thus, efficacy at higher viral loads is unknown. Patients with a CD4 count less than 200 cells/ mm3 had lower treatment response with DTG/3TC (67% [42/63] vs 76% [42/55]).14,15

The TANGO trial assessed whether switching virologically suppressed patients to DTG/3TC would maintain virologic suppression.16 At 96 weeks, DTG/3TC was noninferior to baseline treatments; in this cohort, 66% had been given COBIboosted EVG with TAF. The study population was 92% male and 79% white, and had no history of virologic failure, limiting the extrapolation of results

Table 1. Selected ART Agents by Drug Class

Generic Name (Abbreviation) Trade Name Dosing Recommendations Adverse Events

Nucleoside Reverse Transcriptase Inhibitors

Abacavir (ABC) Ziagen 600 mg once daily, or 300 mg twice daily • Patients who test positive for HLA-B*5701 are at the highest risk for experiencing HSRs. HLA screening should be done before initiating ABC. • For patients with a history of HSRs, rechallenge is not recommended. • Symptoms of HSRs may include fever, rash, nausea, vomiting, diarrhea, abdominal pain, malaise, fatigue, or respiratory symptoms (eg, sore throat, cough, or shortness of breath). • Some cohort studies suggest an increased risk for MI with recent or current use of ABC, but this risk is not substantiated in other studies.

Emtricitabine (FTC) Emtriva

Lamivudine (3TC) Epivir

Tenofovir alafenamide (TAF) Vemlidy

Tenofovir disoproxil fumarate (TDF) Viread Capsule: 200 mg once daily Oral solution: 240 mg (24 mL) once daily

300 mg once daily, or 150 mg twice daily

1 tablet once daily in combination with other drugs

300 mg once daily, or 7.5 level scoops of oral powder once daily (one level scoop contains 1 g of oral powder) • Minimal toxicity • Hyperpigmentation/skin discoloration • Severe acute exacerbation of hepatitis may occur in patients with HBV/HIV coinfection who discontinue FTC.

• Minimal toxicity • Severe acute exacerbation of hepatitis may occur in patients with HBV/HIV coinfection who discontinue 3TC.

• Renal insufficiency, Fanconi syndrome, and proximal renal tubulopathy are less likely to occur with TAF than TDF. • Osteomalacia and decreases in bone mineral density are less likely to occur with TAF than TDF. • Severe acute exacerbation of hepatitis may occur in patients with HBV/HIV coinfection who discontinue TAF. • Diarrhea, nausea, headache

• Renal insufficiency, Fanconi syndrome, proximal renal tubulopathy • Osteomalacia, decrease in BMD • Severe acute exacerbation of hepatitis may occur in patients with HBV/HIV coinfection who discontinue TDF. • Asthenia, headache, diarrhea, nausea, vomiting, flatulence

Non-Nucleoside Reverse Transcriptase Inhibitors

Doravirine (DOR) Pifeltro 1 tablet once daily

Efavirenz (EFV) Sustiva 600 mg once daily, at or before bedtime

Etravirine (ETR) Intelence

Rilpivirine (RPV) Edurant 200 mg twice daily following a meal

25 mg once daily with a meal • Nausea • Dizziness • Abnormal dreams

• Rash • Neuropsychiatric symptoms • Serum transaminase elevations • Hyperlipidemia • Use of EFV may lead to false-positive results with some cannabinoid and benzodiazepine screening assays. • QT interval prolongation

• Rash, including Stevens-Johnson syndrome • HSRs, characterized by rash, constitutional findings, and sometimes organ dysfunction (including hepatic failure), have been reported. • Nausea

• Rash • Depression, insomnia, headache • Hepatotoxicity • QT interval prolongation

Atazanavir (ATV) Reyataz

(ATV/c) Evotaz

Darunavir (DRV) Prezista

(DRV/c) Prezcobix

Ritonavir (RTV) Norvir RTV is currently used at a lower dose of 100-200 mg once or twice daily as a PK enhancer to increase the concentrations of other PIs. All with food Reyataz In ARV-naive patients: rATV 300 mg once daily, or ATV 400 mg once daily In ARV-naive patients with EFV: rATV 400 mg once daily In ARV-experienced patients with TDF: rATV 300 mg once daily with food Unboosted ATV is not recommended Evotaz 1 tablet once daily

In ARV-naive patients or ARV-experienced patients with no DRV mutations: rDRV 800 mg once daily with food

In ARV-experienced patients with one or more DRV resistance mutations: rDRV 600 mg twice daily with food Unboosted DRV is not recommended.

Prezcobix: 1 tablet once daily with food Not recommended for patients with one or more DRV resistance-associated mutations

As a PK booster (or enhancer) for other PIs: 100-400 mg per day in 1 or 2 divided doses (refer to other PIs for specific dosing recommendations) Food Restrictions Tablet: Take with food Capsule and oral solution: to improve tolerability, take with food if possible • Indirect hyperbilirubinemia • PR interval prolongation. First-degree symptomatic AV block has been reported. Use with caution in patients who have underlying conduction defects or who are on concomitant medications that can cause PR prolongation. • Cholelithiasis • Nephrolithiasis • Renal insufficiency • Serum transaminase elevations • Hyperlipidemia (especially with RTV boosting) • Skin rash • Hyperglycemia • Fat maldistribution

• An increase in serum creatinine may occur when ATV is administered with COBI.

• Skin rash: DRV has a sulfonamide moiety; however, incidence and severity of rash are similar in patients with or without a sulfonamide allergy;

Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, and erythema multiforme have been reported. • Hepatotoxicity • Diarrhea, nausea • Headache • Hyperlipidemia • Serum transaminase elevation • Hyperglycemia • Fat maldistribution

• An increase in serum creatinine may occur when DRV is administered with COBI.

• GI intolerance, nausea, vomiting, diarrhea • Paresthesia (circumoral and extremities) • Hyperlipidemia (especially hypertriglyceridemia) • Hepatitis • Asthenia • Taste perversion • Hyperglycemia • Fat maldistribution • Possible increase in frequency of bleeding episodes in patients with hemophilia

Integrase Strand Transfer Inhibitors

Bictegravir (BIC) Biktarvy: 1 tablet PO once daily

Dolutegravir (DTG) Tivicay In ARV-naive or ARV-experienced, INSTInaive patients: 50 mg PO once daily In ARV-naive or ARV-experienced, INSTInaive patients when coadministered with EFV, FPV/r, TPV/r, or rifampin: 50 mg PO twice daily INSTI-experienced patients with certain INSTI mutations (see product label) or with clinically suspected INSTI resistance: 50 mg PO twice daily • Diarrhea • Nausea • Headache • Weight gain

• Insomnia • Headache • Depression and suicidal ideation (rare; usually occurs in patients with pre-existing psychiatric conditions) • Weight gain • HSRs, including rash, constitutional symptoms, and organ dysfunction (including liver injury), have been reported. • Hepatotoxicity

Elvitegravir (EVG) Genvoya: 1 tablet PO once daily with food • Nausea • Diarrhea • Depression and suicidal ideation (rare; usually occurs in patients with pre-existing psychiatric conditions)

Enfuvirtide (T-20) Fuzeon

CCR5 Antagonist

Maraviroc (MVC) Selzentry 90 mg/1 mL SQ twice daily • Local injection site reactions (eg, pain, erythema, induration, nodules and cysts, pruritus, ecchymosis) in almost 100% of patients • Increased incidence of bacterial pneumonia • HSR occurs in less than 1% of patients. Symptoms may include rash, fever, nausea, vomiting, chills, rigors, hypotension, or elevated serum transaminases. Rechallenge is not recommended.

150 mg PO twice daily when given with drugs that are strong CYP3A inhibitors (with or without CYP3A inducers), including PIs (except TPV/r) 300 mg PO twice daily when given with NRTIs, T-20, TPV/r, NVP, RAL, and other drugs that are not strong CYP3A inhibitors or inducers 600 mg PO twice daily when given with drugs that are CYP3A inducers, including EFV, ETR, etc (without a CYP3A inhibitor) • Abdominal pain • Orthostatic hypotension, especially in patients with severe renal insufficiency • Hepatotoxicity, which may be preceded by severe rash or other signs of systemic allergic reactions • Cough • Dizziness • Musculoskeletal symptoms • Pyrexia • Rash • Upper respiratory tract infections

CD4 Post-Attachment Inhibitor

Ibalizumab (IBA) Trogarzo Single loading dose of 2,000 mg IV infusion over 30 min, followed by a maintenance dose of 800 mg IV infusion over 15 min every 2 wk • Diarrhea • Dizziness • Nausea • Rash

to other groups. Adverse events (AEs) were more common in the group that switched to new treatment, which is not surprising given that the control group was stable on their medication. However, AEs commonly associated with DTG were listed as reasons for withdrawal from the trial: depression, anxiety, insomnia, fatigue, and increased weight, but no confirmed virologic withdrawals were seen in the DTG/3TC group, nor resistance development.

A phase 3 trial (DRIVE-FORWARD) of doravirine (DOR) with 3TC/TDF (Delstrigo, Merck) included only treatment-naive HIV patients. Patients were randomized to receive either DOR or darunavir/ ritonavir. The primary end point was the proportion of participants who had a plasma HIV-1 RNA less than 50 copies/mL at 48 weeks. At week 96, a higher proportion of the DOR group (277/383 [73%]) achieved this end point than the DRV group (248/383 [66%]; difference, 7.1%; 95% CI, 0.5%-13.7%).17,18

Selecting an appropriate regimen should be based on patients’ characteristics, including comorbidities, pregnancy status, pill burden, drug–drug interaction, cost, and potential side effects. Table 2 summarizes clinical scenarios that warrant special consideration in initiating therapy.

Treatment-Experienced HIV Patients

The proportion of people in the United States with extensive resistance to ART and limited treatment options has declined markedly since 2012, in large part made possible by the availability of potent new drugs. Bajema et al19 examined data from 27,133 experienced HIV patients, of whom 916 were classified as having limited treatment options (LTO). The prevalence of patients with LTO was 5.2% to 7.5% in 2000-2006, decreased to 1.8% in 2007, and has remained less than 1% after 2012.

Ibalizumab, a humanized IgG4 antibody postattachment inhibitor, was approved in 2018 as an IV infusion every 2 weeks for the treatment of adults with multidrug-resistant (MDR) HIV-1 combined with other antiretroviral medications in patients with limited treatment options. At 48 weeks of the phase 3 trial, significant antiviral activity was found.20

Fostemsavir is an attachment inhibitor in an oral formulation targeting HIV-1 gp120 and preventing viral attachment to CD4 cells, and was recently approved in July 2020.21 The BRIGHTE trial enrolled participants with a viral load of 400 copies/mL or more and at least 2 classes of antiretroviral medications remaining at baseline due to resistance. In the randomized cohort, HIV-1 RNA less than 40 copies/mL was achieved in 53% and 60% of subjects

at weeks 24 and 96, respectively (ITT-E, Snapshot algorithm). Mean changes in CD4+ cell count from baseline continued to increase over time (ie, 90 cells/mm3 at week 24 and 205 cells/mm3 at week 96). In an ongoing phase 3 trial targeting MDR HIV patients, higher viral suppression has been shown in patients on fostemsavir versus placebo.22 These agents provide treatment options for heavily treatment-experienced people living with HIV.

Investigational ART Strategies

Albuvirtide (Frontier Biologics) is a fusion inhibitor that binds to gp41, which is given as a once-weekly subcutaneous injection. In patients with firstline treatment failure, the TALENT study showed albuvirtide with RTV-boosted lopinavir resulted in 80.4% viral suppression when compared with an NRTI group at 66% at 48 weeks.23 There is another ongoing phase 2 multicenter study to evaluate dosage and safety as a long-acting maintenance therapy in virologically suppressed patients.24

Islatravir (ISL, Merck) is a first-in-class NRTTI being investigated as a monotherapy in ART-naive patients. This once-weekly tablet is a long-acting formulation that could increase patient compliance and be used for PrEP in patients who are unwilling or unable to receive a long-acting injection of cabotegravir. In a phase 2b trial (DRIVE2Simplify) of ARTnaive adults with HIV RNA more than 1,000 copies/ mL and a CD4+ count more than 200 cells/mm3 , 3 doses of ISL+DOR+3TC were compared with DOR/3TC/TDF at 24 weeks.25 For weeks 24 to 96, patients receiving ISL+DOR+3TC were switched to ISL+DOR. At week 96, 5.5% of the ISL+DOR treatment groups had protocol-defined virologic failure compared with 3.2% in the DOR/3TC/TDF group. However, all these individuals had fewer than 80 copies/mL HIV-1 RNA levels, and 5 out of 7 had baseline HIV-1 RNA more than 100,000 copies/ mL. In the ISL+DOR groups, 82.2% had more than 1 adverse event compared with 87.1% in the DOR/3TC/TDF groups; drug-related AEs occurred in 7.8% and 22.6%, and serious AEs were noted in 5.6% and 9.7%, respectively. No participant in any treatment group met criteria for resistance testing (all confirmed HIV RNA for protocol-defined virologic failure, <80 copies/mL). Given how promising these early results are, drug-eluting implant devices are being studied for prolonged ISL release in rodents, and studies have shown maintenance

Until an HIV vaccine is available, testing and early ART are crucial.

plasma levels of ISL for more than 6 months resulting in a 1.6-log decrease of viral load.26,27

A monthly long-acting, intramuscular injection of a 2-drug regimen of cabotegravir and RPV (ViiV Healthcare and Janssen) was compared with standard oral regimens in several studies (ATLAS, FLAIR, and LATTE-2). In FLAIR,28 ART-naive adults with HIV-1 RNA more than 1,000 copies/mL were started on DTG/ABC/3TC and a subset switched to CAB plus oral RPV prior to initiating a long-acting IM injection of the same combination. Half of those who remained on DTG/ABC/3TC were directly switched to an IM injection of long-acting CAB+RPV and half were given CAB+RPV orally for 4 weeks prior to initiating the long-acting injection. Whether patients elected to initiate the long-acting injection or an oral regimen lead-in, 99.1% and 93.4% had less than 50 copies/mL at 24 weeks after the switch, respectively. There were no fatal AEs and roughly equal percentages of AEs in the direct-toinjection and oral lead-in groups.28 Switching to an injection of this long-acting regimen may significantly help to maintain patients who have difficulty with daily medication, and this study suggests that an oral lead-in of CAB+RPV may not be necessary. CAB was submitted to the FDA in August 2020, and is currently awaiting a decision. However, the FDA did grant a breakthrough therapy designation for CAB for HIV PrEP on November 18, 2020.11

Conclusion

Until an effective vaccine is available, identification and prompt initial treatment of HIV infection are of utmost importance. Our goals for the treatmentnaive patient are to begin therapy as soon as possible; an integrase is the backbone of therapy; strive for a single-pill combination daily regimen; and always

Table 2. Recommended Initial Regimens for Certain Clinical Situations These regimens are effective and tolerable but have some disadvantages when compared with the most common initial regimens or have less supporting data from randomized clinical trials.

INSTI Plus 2 NRTIs:

• EVG/c/(TAF or TDF)a/FTC (BI)

Boosted PI Plus 2 NRTIs:

• In general, boosted DRV is preferred over boosted ATV • (DRV/c or DRV/r) plus (TAF or TDF)a plus (FTC or 3TC) (AI) • (ATV/c or ATV/r) plus (TAF or TDF)a plus (FTC or 3TC) (BI) • (DRV/c or DRV/r) plus ABC/3TC—if HLA-B*5701 negative (BII)

NNRTI Plus 2 NRTIs:

• DOR/TDFa/3TC (BI) or DOR plus TAFa/FTC (BIII) • EFV plus (TAF or TDF)a plus (FTC or 3TC) • EFV 600 mg plus TDF plus (FTC or 3TC) (BI) • EFV 400 mg/TDF/3TC (BI) • EFV 600 mg plus TAF/FTC (BII) • RPV/(TAF or TDF)/FTC (BI)—if HIV RNA <100,000 copies/mL and

CD4 count >200 cells/mm3

Regimens to Consider When ABC, TAF, And TDF Cannot Be Used or Are Not Optimal:

• DTG/3TC (AI), except for individuals with HIV RNA >500,000 copies/mL, HBV coinfection, or in whom ART is to be started before the results of HIV genotypic resistance testing for reverse transcriptase or HBV testing are available • DRV/r plus RAL twice a day (CI)—if HIV RNA <100,000 copies/mL and CD4 count >200 cells/mm3 • DRV/r once daily plus 3TCa (CI)

Rating of Recommendations: A = Strong; B = Moderate; C = Optional

Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials, observational cohort studies with long-term clinical outcomes, relative bioavailability/bioequivalence studies, or regimen comparisons from randomized switch studies; III = Expert opinion

a TAF and TDF are two forms of TFV approved by FDA. TAF has fewer bone and kidney toxicities than TDF, while TDF is associated with lower lipid levels. Safety, cost, and access are among the factors to consider when choosing between these drugs. Note: The following are available as coformulated drugs: ABC/3TC, ATV/c, BIC/ TAF/FTC, DOR/TDF/3TC, DRV/c, DRV/c/TAF/FTC, DTG/3TC, DTG/ABC/3TC, EFV (400 mg or 600 mg)/TDF/3TC, EFV/TDF/FTC, EVG/c/TAF/FTC, EVG/c/ TDF/FTC, RPV/TAF/FTC, RPV/TDF/FTC, TAF/FTC, TDF/3TC, and TDF/FTC.

3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; ARV, antiretroviral; ATV, atazanavir; ATV/c, atazanavir/cobicistat; ATV/r, atazanavir/ritonavir; BIC, bictegravir; CD4, CD4 T lymphocyte; DOR, doravirine; DRV, darunavir; DRV/c, darunavir/cobicistat; DRV/r, darunavir/ritonavir; DTG, dolutegravir; EFV, efavirenz; EVG, elvitegravir; EVG/c, elvitegravir/cobicistat; FDA, Food and Drug Administration; FTC, emtricitabine; HLA, human leukocyte antigen; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RAL, raltegravir; RPV, rilpivirine; STR, single-tablet regimen; TAF, tenofovir alafenamide; TFV, tenofovir; TDF, tenofovir disoproxil fumarate

Reproduced from Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Adult and Adolescent Panel on Antiretroviral Guidelines for Adults and Adolescents. Department of Health and Human Services. Accessed November 20, 2020. https://clinicalinfo.hiv.gov/en/guidelines/ adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive

emphasize the importance of adherence. Soon, long-acting injectables and pills will likely be available.

References

1. CDC. HIV Surveillance. Accessed December 1, 2020. https://www. cdc.gov/hiv/library/reports/hiv-surveillance/vol-31/index.html 2. US Preventive Services Task Force, Owens DK, et al. JAMA. 2019;321(23):2326-2336. 3. Thompson MA, et al. Clin Infect Dis. 2020. doi: 10.1093/cid/ciaa1391 4. Labhardt ND, et al. JAMA. 2018;319(11):1103-1112. 5. Coffey S, et al. AIDS. 2019;33(5):825-832. 6. US Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. 2019. Accessed December 1, 2020. https://bit.ly/3oAt4xN-idse 7. Torok ME, et al. Clin Infect Dis. 2011;52(11):1374-1383. 8. Boulware DR, et al. N Engl J Med. 2014;370(26):2487-2498. 9. Abdool Karim SS, et al. N Engl J Med. 2010;362(8):697-706. 10. IAVI and Scripps Research join efforts with NIH to expedite development of globally accessible and affordable HIV antibody combination products. July 9, 2020. Accessed October 23, 2020. https://bit. ly/3fVVIWS-IDSE 11. ViiV Healthcare receives FDA breakthrough therapy designation for investigational, long-acting cabotegravir for HIV prevention; November 17, 2020. https://bit.ly/3luONVM-IDSE 12. Apostolova N, et al. J Antimicrob Chemother. 2015;70(10):2693-2708. 13. Llibre JM, et al. Lancet. 2018;391(10123):839-849. 14. Cahn P, et al. Lancet. 2019;393(10167):143-155. 15. Cahn P, et al. J Acquir Immune Defic Syndr. 2020;83(3):310-318. 16. van Wyk J, et al. Clin Infect Dis. 2020;71(8):1920-1929. 17. Molina JM, et al. Lancet HIV. 2020;7(1):e16-e26. 18. Molina JM, et al. Lancet HIV. 2018;5(5):e211-e220. 19. Bajema KL, et al. AIDS. 2020;34(14):2051-2059. 20. Emu B, et al. NEngl J Med. 2018;379(7):645-654. 21. Nowicka-Sans B, et al. Antimicrob Agents Chemother. 2012;56(7):3498-3507. 22. Kozal M, et al. NEngl J Med. 2020;382(13):1232-1243. 23. Wu HY, et al. SSRN. 2018. doi: dx.doi.org/10.2139/ssrn.3309414 24. Albuvirtide and 3BNC117 as long-acting maintenance therapy in virologically suppressed subjects. Accessed October 23, 2020. https://clinicaltrials.gov/ct2/show/NCT03719664 25. Molina J, et al. 2020 International Congress on Drug Therapy in HIV Infection; October 5-8, 2020; Glasgow, United Kingdom. Abstract O415. 26. Barrett SE, et al. Antimicrob Agents Chemother. 2018;62(10). 27. 28. Schurmann D, et al. Lancet HIV. 2020;7(3):e164-e172. D’Amico R, et al. 2020 International Congress on Drug Therapy in HIV Infection; October 5-8, 2020; Glasgow, United Kingdom. Abstract O414.

About the Authors

Hind Alrowais, MD, is an infectious diseases fellow at Ochsner Medical Center in New Orleans, Louisiana.

Amy K. Feehan, PhD, is a clinical infectious disease research scientist at Ochsner Health.

Julia Garcia-Diaz, MD, MSc, FACP, FIDSA,

CPI, is the director of clinical research, and an associate professor at the Ochsner Clinical School, University of Queensland in Brisbane, Australia; and a clinical assistant professor at Tulane University School of Medicine, Ochsner Medical Center in New Orleans, Louisiana.