28th Virtual Conference on Retroviruses and Opportunistic Infection
March 7-10, 2021 |
Eric S. Daar, M.D.
Chief, Division of HIV Medicine
Harbor-UCLA Medical Center
Professor of Medicine
David Geffen School of Medicine at UCLA
The 28th Virtual Conference on Retroviruses and Opportunistic Infections (CROI 2021) was very well organized with a great mix of HIV science interspersed with COVID-19 presentations, acknowledging that many in HIV world have been dispatched to take on the challenge of the new pandemic. This review will focus on select studies in these areas of research. I will touch on the presentations that I thought were particularly interesting, providing a summary that includes what I considered the "headlines" followed by "study findings/Interpretation." Notably, there were several presentations from this meeting that have, or will have substantial impact on the treatment and prevention of HIV and COVID-19 around the world.
Throughout the conference there were several very important presentations related to COVID-19. Some of the highlights related to impact of HIV coinfection as well as studies of prevention and treatment.
• COVID-19 hospitalization and mechanical ventilation in the National COVID Cohort Collaborative was higher amongst solid organ transplant patients and those with HIV than those without either, with much of the impact in the latter group related to comorbid conditions.
• Bamlanivimab (anti-SARS-CoV-2 monoclonal antibody) prevents infection as well as morbidity and mortality in residents of nursing-homes.
• Casirivimab plus imdevimab (anti-SARS-CoV-2 monoclonal antibodies) prevent infection in household contacts.
• Bamlanivimab plus etesevimab (anti-SARS-CoV-2 monoclonal antibodies) reduce the risk of hospitalizations and death in non-hospitalized patients with mild to moderate COVID-19.
• The National COVID Cohort Collaborative includes 39 centers with a large cohort of individuals with documented SARS-CoV-2 infection were analyzed. Between 2020-2021 there were approximately 500,000 persons with SARS-CoV-2 infection, 4633 being solid organ transplant recipients and 2932 being HIV-infected (1). Numerous variable was adjusted for in the analysis. The study found that there was a marked increased risk of both hospitalizations and mechanical ventilation in these groups compared to those without. Upon adjusting for important covariates it was found that a considerable amount of the increased risk in those with HIV was associated with presence of comorbid conditions such as cardiopulmonary and renal disease. This is one of the larger studies that was able to carefully review the relationship between these conditions and worse outcomes with COVID-19 and supports importance of careful monitoring of these individuals when found to be SARS-CoV-2 infected. Although COVID-19 vaccine efficacy data is limited in these populations, it remains important that they strongly consider getting vaccinated as soon as this is possible. They should also be considered prime targets for new therapeutics for mild to moderate disease as they become available.
• Bamlanivimab is an anti-SARS-CoV-2 monoclonal antibody that is being studied for treatment and prevention of COVID-19. BLAZE-2 is a longitudinal, double blind, placebo-controlled study was designed to see if a single infusion of 4200 mg of bamlanivimab in residents of skilled nursing or assisted living facility during outbreak settings can prevent infection and disease progression (2). The group developed a program with medical vans that could be dispatched to sites where outbreaks were present and offer this treatment as part of a placebo-controlled trial. The primary endpoint was symptomatic disease with secondary endpoint of infection. The study included 484 participants receiving bamlanivimab and 482 placebo when combining residents and staff. The investigators reported data on the 181 residents that received bamlanivimab and 139 that received placebo. With 80% reduction (p<0.001) in symptomatic disease with 4 deaths, all in placebo group. There was a 76% reduction in SARS-CoV-2 detection in the bamlanivimab group, and those in that study arm that did get infected had lower levels of nasal viral shedding than those infected in placebo study arm.
This study provides strong evidence that in the setting of an outbreak in nursing home that uninfected resident may derive substantial benefits from this treatment. An important caveat for all monoclonal antibody products in development relates to the potential impact circulating variants of concern may have on overall efficacy. With time, the prevalence of circulating variants that are less susceptible to select monoclonal antibodies may impact outcomes. This is an area of intense interest and investigation and must be considered as molecular surveillance is increasing, as is our knowledge regarding susceptibility of variant of concern to the different antibodies under development. It is also important to note that at the time of CROI 2021, bamlanivimab was available through Food and Drug Administration (FDA) Emergency Use Authorization (EUA) alone or with etesevimab for outpatients with mild to moderate COVID-19, but not for post-exposure prophylaxis.
• Casirivimab plus imdevimab are a combination of anti-SARS-CoV-2 monoclonal antibodies being developed for prophylaxis and treatment. At CROI 2021 interim data was presented on the first 409 individuals randomized to multiple subcutaneous injections of antibodies (600 mg of each) or placebo within 96 hours of household member they were exposed to being diagnosed with infection (3). Some of the participants were ultimately found to already be infected at baseline, while others were not. The data presented focused on the latter group and followed them for PCR evidence of infection and outcomes such as symptomatic disease and progression to severe disease. The study demonstrated symptoms in 8 of 223 placebo and 0 monoclonal antibody recipients. PCR positive infection in 23 placebos versus 10 in monoclonal antibodies group with approximately 100-fold lower level of nasal viral shedding in the treated group than placebo. These findings demonstrate that those within 96 hours of a household exposure can benefit from the use of this subcutaneously administered product. As noted as an important caveat for the bamlanivimab post-exposure prophylaxis study above, there are concerns about the impact of circulating variants of concern, although at least based upon in vitro data most of these variants have some level of preserved susceptibility to at least one of the two antibodies utilized in this study. It is also important to note that at the time of CROI 2021, casirivimab plus imdevimab were only available through FDA EUA for treatment of outpatients with mild to moderate COVID-19, but not for post-exposure prophylaxis.
• Bamlanivimab plus etesevimab are anti-SARS-CoV-2 monoclonal antibodies being developed for treatment of COVID-19. The presentation at CROI 2021 was BLAZE-1 which is a phase 3, double-blind, placebo-controlled trial with 1:1 randomization of outpatient participants with documented SARS-CoV-2 infection and mild to moderate COVID-19 at high risk for disease progression. Treated within 3 days of diagnosis, 518 receiving monoclonal antibodies at a dose of 2800 mg of each, and 517 placebo with primary endpoint of hospitalization or death (4). There were 36 (7%) hospitalization or any cause death in placebo group versus 11 (2.1%) in the monoclonal antibody group for ~70% reduction. There were 10 deaths, 9 COVID-19 related, all of which occurred in the placebo group. They also noted lower levels of nasal viral shedding and shorter time to resolution of symptoms. It is notable that these results are similar to that seen in smaller phase 2 studies using bamlanivimab monotherapy, bamlanivimab plus etesevimab and casirivimab plus imdevimab. These phase 2 studies were much smaller and less definitive, but did result in FDA EUA for this same study population. With the phase 3 results from bamlanivimab plus etesevimab, the NIH and IDSA guidelines panel have recommended this combination be used in those with mild to moderate COVID-19 that are at high risk for severe disease, using specific criteria outlined in EUA. It is important to note the potential impact variants of concern could have on the activity of these monoclonal antibodies in the future, an area of ongoing research. While the EUA makes bamlanivimab/etesevimab available at 700/1200 mg dose, different than what was used in this study, Lilly did report in a press release that a study of this dose in 510 active and 250 Placebo showed similar results. This data will hopefully be fully presented in near future.
There were several studies of non-COVID-19 related infections of particular interest, including related to treatment of HCV and tuberculosis.
• The MINMON/ACTG 5360 study showed that HCV cure rates were 95% in those provided 12 weeks of sofosbuvir plus velpatasvir with little follow-up.
• The Study 31/A5349 showed that a regimen of isoniazid, rifapentine, moxifloxacin with pyrazinamide for 2 months followed by 2 months of same without pyrazinamide (4 months total) was as effective as standard 6-month regimen in HIV-infected individuals.
• The MINMON/ACTG 5360 study was a phase IV, open-label study conducted in United States, Brazil, Thailand, Uganda and South Africa (5). The study enrolled 400 HCV-infected individuals and provided then with 84 tablets of sofosbuvir/velpatasvir. The primary endpoint was sustained virologic response based upon HCV RNA less than lower limits of detection in first sample collected after 22 weeks of stopping treatment. Eligible participants were untreated HCV infection with either no cirrhosis or compensated cirrhosis. Approximately 50% were HIV-infected with high CD4 and viral load suppression. The study excluded those with chronic hepatitis B infection. The novel part of this study was that no baseline genotype was required pre-enrollment since a pan genotypic regimen was used, and there were no study visits during the 12 weeks of dosing. Of those enrolled, 379 of 399 (95%) had sustained virologic response (SVR) (95% CI 92.4 to 96.7). There were only 20 without SVR, at least 67% of which reported poor adherence. In addition, serious adverse events were uncommon, reported in 3.5% of participants. These results demonstrate that in a stable and adherent population, treatment can be streamlined to limit initial collection of baseline information, no follow-up visits for laboratory monitoring and have SVR rates that are similar to what was seen in intensive randomized-controlled trials. Such simplicity could markedly increase access to therapy for those in need.
• The Study 31/A5349 was designed to determine if a 4-month regimen for tuberculosis with rifapentine and moxifloxacin was as effective as a standard 4-drug regimen for 6 months. It was an international, randomized, open-label phase 3, non-inferiority trial of standard isoniazid, rifampin, ethambutol plus pyrazinamide for 2 months followed by isoniazid plus rifampin for an additional 4 months (Control, 6 months total). This was compared to investigational regimens of:
• isoniazid, rifapentine, pyrazinamide and ethambutol for 2 months followed by isoniazid plus rifapentine for an additional 2 months (rifapentine group, 4 months total), or
A subset of 214 were HIV infected with CD4+ T-cells >100 cells/uL, on efavirenz-based antiretroviral regimen with VL <200 copies/mL (6). All participants had culture confirmed pulmonary tuberculosis susceptible to all drugs. Primary endpoint was tuberculosis-free survival 12 months after randomization with non-inferiority margin of 6.6%. Amongst the HIV-infected group there were 71 in 6-month control group, 71 in 4-month rifapentine group, and 72 in 4-month rifapentine-moxifloxacin study arm.
• isoniazid, rifapentine, moxifloxacin plus pyrazinamide for 2 months followed by isoniazid, rifapentine, moxifloxacin for an additional 2 months (rifapentine-moxifloxacin group, 4 months total)
In those assessable, the percent achieving primary endpoint of tuberculosis-free survival was 85% in the controls, 91% in the rifapentine-moxifloxacin group and 74% in the rifapentine group. Analyses showed that the 4 month rifapentine-moxifloxacin study arm met the pre-specified non-inferiority criteria. Adverse events, serious adverse events and deaths were similar across groups, being numerically lower for the rifapentine-moxifloxacin study arm. The investigators concluded that the rifapentine-moxifloxacin for 4 months was non-inferiority to standard 6-month regimen in both those with and without HIV infection and that this was a major milestone in pursuit of shorter tuberculosis treatment regimens.
• The Prevenir study showed high level of effectiveness of on-demand PrEP amongst men who have sex with men (MSM) in Paris.
• Updated data from HPTN 083 confirm efficacy of long acting cabotegravir (LA CAB) for PrEP in MSM and transgender women (TGW) with infections occasionally occurring despite good adherence and with associated emergent resistance.
• Islatravir pharmacokinetics after oral dosing show levels consistent with potential for once monthly oral dosing for PrEP.
• Islatravir implant demonstrates levels that could support once yearly use for PrEP.
• The Prevenir Study was an open-label study conducted in Paris where primarily MSM at high risk for acquiring HIV were offered either once-daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or on-demand TDF/FTC dosed as 2 tablets 2-24 hours prior to sex and then 24 and 48 hours after the pre-sex dose, so called 2-1-1 regimen (7). The primary end point of the study was to reduce the number of new HIV diagnoses among MSM in Paris. At this meeting they reported the results from 3059 enrolled individuals, with 1544 selecting once daily TDF/FTC and 1515 the on-demand 2:1:1 regimen. The investigators reported 3 incident infections in each group with an incidence of 0.12 infections/100 patient-years of follow-up. Tolerability was good with only 15-20% condom use and frequent sexually transmitted infections. Adverse events were somewhat more common in the on-demand group, mostly related to mild GI events, which may reflect the use of the 2 pill simultaneously prior to sexual exposure. The placebo-controlled iPergay study of the 2:1:1 regimen had limitations because it was stopped early with only approximately 200 people in the investigational study arm, who also had frequent sexual exposures resulting in frequent dosing. This open-label study was much large with approximately 1500 participants receiving 2:1:1 regimen. It is also notable that this regimen is supported by several guidelines as an optional strategy, particularly for those engaging in relatively infrequent sex. In contrast, this regimen is not FDA approval or included in most recent Centers for Disease Control and Prevention guidelines, while it is included in the International Antiviral Society-USA guidelines as an option for MSM who have infrequent sexual activity. It is also important to note that Prevenir is not a randomized controlled study and does not provide sufficient data to justify its use in non-MSM.
• HPTN 083 results were recently reported after independent data safety monitoring board recommend it be stopped. This was a randomized, controlled trial of MSM and TGW at high risk for HIV acquisition who were randomized to either once daily TDF/FTC or every two-months intra-gluteal LA CAB, a new integrase strand transfer inhibitor (INSTI) at a dose of 600 mg. There was a 5 week lead in phase of oral CAB to assure it was tolerated, before continuing with LA CAB regimen. Reported at this meeting was the clear superiority of LA CAB over TDF/FTC with 12 cases in former and 39 in the latter study arms for rate of 0.37 versus 1.22 per 100 person-years follow-up (8). Dried blood spot analysis in a subset of TDF/FTC participants found levels below which efficacy would be expected in nearly 25% of participants. In contrast, adherence in the every 2-month injection group was quite high. Safety was good in both study arms. Further analysis looked at those that became infected in the LA CAB study arm. They found that 4 were unknowingly infected at baseline. Another 5 became infected after gaps since they last received they doses and another 3 during the lead in phase. There were 4 that became infected despite having consistently received LA CAB doses, 2 having INSTI resistant mutations. Collectively this data confirms that LA CAB is highly effective and well tolerated. It does note that it is not 100% effective, that there are some risks of selecting for resistant virus.
• Islatravir is a nucleoside reverse transcriptase translocation inhibitor that is very potent, has broad activity against multiple viruses with resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and has a long half-life. It is being developed for both HIV treatment and prevention. At this meeting there were two early studies of potential role in prevention. The first demonstrated PK of once monthly oral dosing for potential use. Assuming adequate levels are achieved in rectal and vaginal mucosa this could be an important advance to overcome limitations of current therapy (9). The other study evaluated 3 different doses versus placebo of an implant that can be introduced subcutaneously and slowly release levels for PrEP (10). They noted that with 8 low risk, HIV negative individuals receiving all three doses of 48, 52 and 62 mg or placebo tolerated the product well with usual side effects of an implant, e.g. hematoma, erythema, tenderness, but generally mild and self-limiting. They also found that PK data suggested that the highest dose would maintain levels above predicted necessary for prevention for in excess of 12 months. Both strategies remain in early stages of development for PrEP, but would provide important advances over existing agents. Announced shortly after the meeting was a collaboration between Gilead Sciences who are developing a long-acting first in class capsid inhibitor and Merck, who are developing islatravir. Certainly these two products could be very complimentary from a treatment perspective and I am sure we will learn more about what they have in mind in the near future.
There were several important studies of antiretroviral therapy. I will summarize a few select studies and encourage those registered for CROI 2021 to look on-line for others of potential interest that I did not summarize.
• DoLPHIN2 final results show safety and efficacy of dolutegravir (DTG) plus tenofovir alafenamide/lamivudine (TAF/3TC) in late stages of pregnancy.
• IMPAACT 2010 results show safety and efficacy of DTG plus TAF/FTC or TDF/FTC started in later stages of pregnancy than DoLPHIN2.
• ATLAS-2M results showed safety and high levels of efficacy out to 96 weeks of LA CAB plus LA rilpivirine given every 2 versus ever 1 month in stably suppressed individuals.
• The NADIA Trial showed that those failing first line nonnucleoside reverse transcriptase inhibitors (NNRTI) plus TDF/FTC (or 3TC) with extensive underlying NRTI resistance can successfully be treated with darunavir/ritonavir or DTG combined with TDF/FTC, even if none of the NRTIs are fully active or if K65R that confers resistance to TDF is present.
• Lenacapavir, a first-in-class capsid inhibitor that can be administered subcutaneously every 6 months is a very potent drug in highly treatment experienced persons with multi-class drug resistant virus.
• DoLPHIN2 is a randomized controlled trial of HIV-infected women presenting at or after 28 weeks of pregnancy and randomized to DTG + TDF/3TC (n=135) or efavirenz (EFV)/TDF/FTC (n=133). Previous results demonstrated that for the primary endpoint of viral suppression at time of delivery, both were quite successful, but DTG-based therapy was superior with median time to viral suppression to <50 copies/mL of 4.14 versus 12.14 weeks, for the DTG versus EFV groups, respectively. At this meeting they presented the final 72 week results and reported that suppression was durable in both groups with good maternal and fetal safety profiles with no signals of worse outcomes in those receiving DTG versus EFV (11). There were 3 mother to fetal transmission events in the DTG group, all thought to be in utero, compared to 1 in the EFV group thought to have occurred postpartum. Viral failure did occur more frequently in the EFV group at 8 (6.4%) versus 3 (2.4%) in those assigned DTG-based therapy. The clinical relevance of this study is high for treatment in resource limited settings but also in the United States where DHHS perinatal guidelines panel recently modified their recommendation for DTG in pregnancy being a preferred option at all stages of pregnancy and even in women who may become pregnant. This change in guidelines results from previous updated data from Tsepamo study in Botswana that showed the risk of neural tube defects in infants exposed to DTG at conception was very low.
• IMPAACT 2010 was a randomized, controlled trial of DTG plus TAF/FTC (n=217), DTG plus TDF/FTC (215) or EFV/TDF/FTC (211) in pregnant women between 14 and 28 weeks of pregnant. This study provided a great opportunity to assess the utility of DTG in pregnancy since it is now a preferred option in resource limited settings. It also allowed for comparison of TAF/FTC versus TDF/FTC-based regimen. Results show that safety and efficacy of DTG plus TAF/FTC or TDF/FTC started in later stages of pregnancy than DoLPHIN2. Overall rates of viral suppression were high in all groups, 96.3% in combined DTG arms, versus 96.4% in the EFV group at week 50 postpartum (12). As in DoLPHIN2, viral failure did occur more frequently in the EFV group (10.4%) than DTG/TAF//FTC (4.1%) and DTG TDF/FTC (5.1%) with modest differences in pregnancy events; or maternal or infant grade 3 or 4 adverse events postpartum. As noted in discussion of DoLPHIN2 study, these data have implications around the world for use of DTG in pregnancy. In addition, this represents a strong comparison showing the safety and efficacy in pregnancy of TAF versus TDF, which is increasingly being used during pregnancy.
• ATLAS-2M results showed safety and high levels of efficacy out to 96 weeks of LA CAB plus LA rilpivirine (RPV) given every 2-months (dosed at 600 mg/900 mg) versus ever 1-month (dosed at 400 mg/600 mg) in those previously suppressed on antiretroviral therapy. As a novel 2-drug regimen administrated via a unique vehicle, data with extended follow-up is important. We had seen this for the registrational trials for once monthly dosing, FLAIR and ATLAS, and now at this meeting for every 2-month dosing (13). Overall, levels of sustained viral suppression remained very high in both study arms. Tolerability and acceptability was also good for both arms, although favoring every 2-month dosing. There were a few cases of virologic failure, 2 in once-monthly and 9 in twice-monthly, with INSTI resistance identified in both. Overall, these results support this dosing frequency at a time when many agencies, including the FDA have approved the once-monthly dosing regimen.
• The NADIA Trial showed that those failing first line NNRTI plus TDF/FTC with extensive underlying NRTI resistance can successfully be treated with boosted darunavir (DRV) or DTG combined with either zidovudine/lamivudine (ZDV/3TC) or TDF/FTC even if none of the NRTIs are fully active (14). The study design was very interesting and filled some holes left from the previous pivotal trials of first-line NNRTI failures, SECOND LINE, ERNEST and A5273 (SELECT). The previous trials all showed that first-line NNRTI failures could be treated with lopinavir/ritonavir (LPV/r) with 2-3 NRTIs or LPV/r plus Raltegravir (RAL). These findings held up even in those in which there were no fully active NRTIs in the regimen. The DAWNING study showed that first-line NNRTI failure was more successfully treated with DTG plus 2 NRTIs than LPV/r plus 2 NRTIs, with both arms needing to include at least one fully active NRTI based upon drug resistance testing. Unanswered questions included whether a more contemporary protease inhibitor, e.g. boosted DRV would work as well as LPV/r, and whether DTG in this setting needed to be combined with at least one fully active NRTI. There was also the open question as to how best use NRTIs in those in which resistance data was not available.
NADIA was a randomized controlled trial of people failing first-line EFV/TDF/FTC who were randomized first to DTG versus DRV/r and then in each arm to TDF/FTC or ZDV/3TC. The study included approximately 464 individuals, about half of which had M184V and K65R mutations, i.e. significant resistance to the TDF/FTC. Overall, virologic responses at 48 weeks were excellent, DTG (90.2%) and boosted DRV (91.7%) for primary endpoint of <400 copies/mL and for <50 copies/mL 80.9 and 79.5%, respectively. Virologic failure was rare with no resistance identified to DRV and 4 with resistance to DTG, 3 of which were in the ZDV/3TC arm and only one in the TDF/FTC group. This study provides strong evidence that those failing first-line NNRTI therapy, regardless of amount of NRTI resistance can be treated with boosted DRV or DTG with TDF/FTC. One can further extrapolate from this data to other clinical settings where boosted DRV or DTG are fully active and NRTI resistance is known to be high or is uncertain at time treatment decisions are being made.
• Lenacapavir, a first-in-class capsid inhibitor was studied in highly treatment-experience individuals in the CAPELLA study (15). Participants had viral loads at screening >400 copies/mL with resistance to at least 2 agents from at least 3 classes. Those still >400 copies/mL at baseline were randomized 2:1 to add lenacapavir as a 600 mg dose on day 1 and 2, and 300 mg at day 8, added to failing regimen. There were 36 suppressed at baseline who received open-label therapy. The primary endpoint was at least 0.5 log reduction in viral load from baseline to day 15. At day 15 participants received a subcutaneous dose of 927 mg every 6-months along with an optimized background regimen. The lenacapavir group had 88% who met primary endpoint versus only 17% in the control group. with mean decrease in VL from baseline to day 15 of -1.93 versus -0.29 log10 copies/mL. at week 26 of follow-up, 19 of 26 had viral loads of <50 copies/mL. There were no drug-related adverse events except for 46% with injection site reactions, 82% of which were described as grade 1.
28th Virtual CROI 2021 was an excellent meeting, extremely well organized and presented in virtual format. There were numerous highly relevant studies related to COVID-19, HIV coinfections as well as prevention and treatment. I have focused on select studies in each of these areas that are likely to impact the field in the near future.
CROI webcasts: http://www.croiwebcasts.org/s/2021croi/Symposium-04
Conflicts: In the last year Eric Daar has received research support from Gilead, Merck, ViiV and has been a consultant for Gilead and Merck.
1. Sun J, Patel R, Madhira V, et al. COVID-19 hospitalization among people with HIV or solid organ transplant in the US. 28th CROI 2021, abstract 103.
2. Cohen MS, Nirula A, Mulligan M, et al. Bamlanivimab prevents COVID-19 morbidity and mortality in nursing-home setting. 28th CROI 2021, abstract 121.
3. O'Brien MP, Neto EF, Chen K-C, et al. Casirivimab with imdevimab antibody cocktail for COVID-19 prevention: Interim results. 28th CROI 2021, abstract 123.
4. Dougan M, Nirula A, Gottlieb RL, et al. Bamlanivimab + etesevimab for treatment of COVID-19 in high-risk ambulatory patients. 28th CROI 2021, abstract 122.
5. Solomon SS, Wagner-Cardoso S, Smeaton LM, et al. A simple and safe approach to HCV treatment: Findings from the A5360 (Minmon) trial. 28th CROI 2021, abstract 135.
6. Pettit A, Nahid P, Phillips PP, et al. Rifapetine +/- moxifloxacin for pulmonary tuberculosis in people with HIV. 28th CROI 2021, abstract 130.
7. Molina J-M, Ghosn J, Delaugerre C, et al. Incidence of HIV infection with daily or on-demand oral PrEP with TDF/FTC in France. 28th CROI 2021, abstract 148.
8. Marzinke M, Grinsztejn B, Fogel J, et al. Laboratory analysis of HIV infections in HPTN 083: Injectable CAB for PrEP. 28th CROI 2021, abstract 153.
9. Patel M, Zang X, Cao Y, et al. Islatravir PK threshold & dose selection for monthly oral HIV-1 PrEP. 28th CROI 2021, abstract 87.
10. Matthews RP, Zang X, Barrett S, et al. Next-generation islatravir implants projected to provide yearly HIV prophylaxis. 28th CROI 2021, abstract 88.
11. Malaba TR, Nakatudde I, Kintu K, et al. DoLPHIN2 final results dolutegravir vs efavirenz in late pregnancy to 72 W postpartum. 28th CROI 2021, abstract 175.
12. Chinula L, Brummel S, Ziemba L, et al. Safety/efficacy of DTG vs EFV, TDF vs TAF in pregnancy/postpartum: IMPAACT 2010 Trial. 28th CROI 2021, abstract 177.
13. Jaeger H, Overton ET, Richmond G, et al. Week 96 efficacy and safety of cabotegravir + rilpivirine every 2 months: ATLAS-2M. 28th CROI 2021, abstract 401.
14. Paton N, Musaazi J, Kityo CM, et al. Nucleosides and darunavir/dolutegravir in Africa (NADIA) Trial: 48 wks primary outcome. 28th CROI 2021, abstract 94.
15. Segal-Maurer, Castagna A, Berhe M, et al. Potent antiviral activity of lenacapavir in phase 2/3 in heavily ART-experienced PWH. 28th CROI 2021, abstract 127.