CROI 2018 Summary Report, Eric Daar M.D.
25th Conference on Retroviruses and Opportunistic Infections (CROI) |
March 4-7, 2018
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 25th Conference on Retroviruses and Opportunistic Infections (CROI 2018) was an excellent meeting in Boston that included numerous presentations on HIV pathogenesis, prevention, treatment and comorbidities/coinfections. There were approximately 4000 attendants with 1061 abstracts accepted amongst the 1960 submitted. From this there were 95 oral abstracts and 966 poster presentations with an additional 88 late breaker abstracts.
This review will focus on select studies related to HIV cure research, prevention, comorbidities and coinfections. 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."
Cure research has been on the agenda for several years, but remains in the very early stages of exploration. At this meeting there was one particularly interesting study in a non-human primate model that I thought worth discussing.
• Combination of a broadly neutralizing monoclonal antibody with a Toll-Like Receptor 7 (TLR7) agonist resulted in a marked delay in time to viral rebound in SHIV-infected Rhesus Macaques.
• This study asked the question whether a HIV-1-specific broadly neutralizing monoclonal antibody can be used to target the viral reservoir in SHIV-infected Rhesus Macaques (1). The investigators infected macaques and then treated them with dolutegravir/emtricitabine/tenofovir alafenamide (DTG/FTC/TAF) for 96 weeks. They administered to each group of 11 Macaques either sham, the TLR7 agonist GS-9620, the monoclonal antibody or a combination of the antibody and the TLR7 agonist. Sixteen weeks after the last dose they interrupted treatment and followed closely to assess time to viral rebound. While there was a slight delay in time to rebound in those treated with the TLR7 or antibody alone, there was a highly significant delay in those treated with the combination of agents. In fact, 5 of the 11 in the combination treated group did not experience viral rebound during the 6 months of post treatment interruption follow-up. The investigators noted that the delay could not be explained by presence of residual antibodies in circulation since it was not seen in the antibody alone group and blood levels of antibodies were very low for at least 2 months prior to treatment interruption. It was hypothesized that the outcome was a result of the TLR7 agonist effect on latently infected cells that facilitated binding and clearance by the antibodies. Further study is needed to verify the significance of these important findings.
HIV TRANSMISSION AND PREVENTION
Understanding transmission and ways to prevent HIV spread has resulted in some of the most important advances in clinical research. At this meeting there was interesting data related to transmission around pregnancy and several strategies to reduce the risk of transmission using pre-exposure prophylaxis (PrEP).
• Data from cohorts of HIV-infected women demonstrated an increased risk of HIV acquisition per sex act during pregnancy and postpartum.
• PrEP use is expanding but remains low in many high risk populations.
• Targeted PrEP implementation in New South Wales (EPIC NSW Cohort) resulted in a decreased rate of infection in the cohort as well as across the population.
• Targeted PrEP implementation in San Francisco has been associated with a decline in new HIV infections.
• Low dose weekly oral MK-8591 was 100% protective against SHIV infection in a non-human primate model.
• An analysis was performed of HIV-uninfected women in stable partnerships with HIV-infected men in Partners in Prevention HSV/HIV transmission and Partners PrEP studies. HIV incidence per 100 person-years of follow-up during early and late pregnancy, as well as during the first 6 months postpartum was compared to those not pregnant or postpartum (2, 3). There were 82 incident infections with incidence per 100 person-years (95% CI) for those nonpregnant or postpartum of 1.3 (0.9, 1.6) compared with 3.8 (1.2, 8.8) in early pregnancy (0-13 weeks), 7.0 (3.7, 12.0) during late pregnancy (14 weeks to delivery) and 4.7 (1.7, 10.2) postpartum (up to 6 months post-delivery or loss of the baby). Further research is needed to fully understand the reason for these findings which may well be multifactorial, representing behavioral and biologic factors. Regardless, these findings suggest that women need to be counseled during pregnancy and post-partum period to minimize their risk of acquiring HIV from infected sex partners.
• PrEP represents a highly effective means of preventing HIV infection of high risk individuals. This realization has led to analyses to identify the effectiveness of roll out of this strategy with an estimated approximately 100,000 unique individuals in United States having been prescribed PrEP. However, it has been estimated that there are more than one million people at high risk for HIV acquisition that might benefit. An analysis by the Centers for Disease Control and Prevention attempted to define roll-out using PrEP prescription data from a national health data company. They further defined the PrEP-to-need ratio (4) as the number prescribed PrEP relative to new HIV diagnoses across groups and by regions of the United States. It is estimated that during the 2nd quarter of 2017 that the PrEP-to-need ratio in the United States was 1.5 with higher ratios in Northeast and West and lower, suggesting low PrEP penetrance, in women and in those living in the South. This type of data provides information about groups and regions that require further outreach and education about PrEP, as well as the need for novel interventions to enhance PrEP uptake where appropriate.
• Several groups have attempted to target PrEP to high risk populations in order to increase PrEP-to-need ratio. The EPIC NSW Cohort directed outreach and PrEP initiation in high risk men who have sex with men with the goal of enrolling more than 90% who fall into this category within the year (5). Investigators identified those at least 18 years of age, HIV-uninfected without symptoms of acute HIV infection and an estimated glomerular filtration rate (eGFR) >60 mL/min as candidates for PrEP. The primary outcome was within-cohort HIV incidence and population effectiveness assessed by change in rate of new HIV infections in the community. It was reported that the within cohort rate was 0.5 per 100 person-years with 2 infections over 3900 person-years follow-up; one never having started PrEP and the other who did not take it prior to the infection. Equally important was the population change in new infections decreasing from 149 to 102 between the before and after implementation period, respectively.
A related study occurred in San Francisco as part of their City-wide getting-to-zero (SFG2Z) consortium. They similarly targeted high-risk individuals showing an increase in MSM on PrEP from 11% in 2014 to nearly 50% in 2017 (6). This was associated, along with the other aspects of the SFG2Z program, including rapid ART initiation and linkage-engagement in care with more than 50% reduction in new HIV diagnoses in the city between 2012 and 2016. Together these studies demonstrate that targeted outreach to high risk individuals that meet criteria for PrEP can be effective in increasing the PrEP-to-need ratios in select communities and be associated with favorable declines in HIV infection rates.
• Although current PrEP is highly effective and generally well tolerated, there is interest in developing new strategies that might be better tolerated or require less than daily dosing. One such agent being pursued is MK-8591, known as EFdA, a novel agent with a long half-life that inhibits reverse transcriptase by preventing translocation. The current study used 3.9 mg/kg per week in non-human primate model using low dose SHIV intrarectal challenge (7). In this study they demonstrated 100% protection with this dose. They further tested doses of 1.3, 0.43 and 0.1 mg/kg per week with the two higher doses being 100% protective in 8 animals at each dose and the lowest dose being protective in 6 of 8 animals. There were no safety issues and this study suggests that this may be a novel agent to pursue in human trials.
There has been substantial data related to when and what to start, as well as switching options in those virologically suppressed and with virologic failure. At this meeting several such studies addressed many of these critically important areas of research.
• When and who to start on antiretroviral therapy:
o The CASCADE Trial showed that starting people in rural villages in Lesotho the day of diagnosis rather than referring to local clinics for treatment resulted in improved rates of linkage to care and virologic suppression.
o Rapid antiretroviral therapy (ART) initiation in San Francisco has been associated with a substantial decline in the time to viral suppression.
o Starting ART in virologic controllers with viral loads less than 500 copies/mL results in decrease in plasma HIV RNA, CD8+ T cell activation and some markers of immune exhaustion.
• First-line ART:
o The first phase of the ANDES Study demonstrated that boosted darunavir (DRV) with lamivudine (3TC) was effective in suppressing plasma HIV RNA in treatment-naïve patients.
• Maintenance therapy:
o Switching virologically suppressed individuals on DTG/abacavir/3TC (DTG/ABC/3TC) single tablet regimen (STR) to bictegravir/FTC/TAF (BIC/FTC/TAF) showed maintenance of high level suppression, no emergent resistance, low incidence of adverse events and similar changes in lipids, bone and renal measures. Another study with similar design enrolled nearly 500 women on stable ART regimens with virtually identical results.
• Second and third-line ART:
o The DAWNING study demonstrated higher rates of virologic suppression in those having failed two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) switched to DTG versus lopinavir/ritonavir (LPV/r) when both were combined with two NRTIs with at least one being fully active. An analysis presented at this meeting suggested modest but significantly greater suppression in those receiving World Health Organization (WHO)-recommended NRTIs than those that did not.
o Study A5288 demonstrated the effectiveness of using drug resistance testing in resource limited setting in those failing LPV/r-based second-line therapy. The study demonstrated good outcomes in those that were integrase strand transfer inhibitor (INSTI)-naïve and LPV/r resistance with predicted susceptibility to boosted DRV when treated with boosted DRV, raltegravir (RAL) and best available NRTIs or etravirine (ETR), if the latter was predicted to be susceptible. In contrast, those without protease inhibitor (PI) resistance who were encouraged to stay on their current regimen with enhanced adherence had low virologic response rates.
Study findings and interpretation:
• The CASCADE Trial was an open-label study conducted in Lesotho to assess the impact same day initiation of ART has on linkage-to-care and viral suppression (8). The study was conducted between 2016 and 2017 where same-day HIV testing was performed in 6655 households in 60 rural villages and 17 urban centers. They identified 278 HIV-infected, treatment-naïve adults and randomized them 1:1 to either start ART the same day, given a 30-day supply of medications and follow-up instructions to nearby treatment center, or simply provided the latter without treatment. Approximately two thirds were women with median CD4 cell count of 350-400 cells/uL. They found that those started on treatment the same day of diagnosis were more likely to have followed-up at the treatment center and be linked to care within 3 months (69 vs. 43%, p<0.001) and to have HIV-1 viral load <100 copies/mL by 6 (50 vs. 34%, p=0.007) and 11-14 months (37 vs. 26%, p=0.05). In addition, in a post-hoc analysis of retention in care at one year there was significantly better outcomes for the same-day versus usual care groups (64 versus 48%, p=0.01). These results provide strong evidence that in rural villages in resource limited setting there are substantial benefits associated with same-day initiation of ART.
• There is very limited data, yet alone randomized trials for same-day initiation of ART in the United States. This strategy was evaluated as part of the SFG2Z Consortium with an accelerated ART initiation program for newly diagnosed individuals (9). The program was started in 2015 after a successful pilot project. All new confirmed HIV infections in the City were referred to care within 5 days and ART started the day of first visit unless there was a contraindication. Between 2013 and 2016 there were relatively stable and high rates of individuals starting on therapy (78-84%); however, there was a marked increase in proportion started on the same day during that interval, being 6% in 2013 and 30% by 2016. Consistent with the goals of the program there was 96% decrease in the days from entering care to starting antiretrovirals during the period of follow-up, from median of 27 days in 2013 to 1 day in 2016. Even more importantly, there was a dramatic decrease in median days to viral suppression; 134 days in 2013, with greater than 50% decline to 61 days in 2016. The latter is likely a reflection of both the rapid initiation of ART as well as increased use of INSTIs as first line therapy. These benefits were seen across a broad range of demographics as well as in those housed and homeless. The results provide strong evidence that a same day start program is feasible and is associated with some tangible benefits. That said, the resources needed to institute the program remain limited and consistent with current Department of Health and Human Services (DHHS) guidelines, probably should still be considered investigational until more data becomes available.
• Study A5308 attempted to define the potential benefits associated with starting HIV controllers on ART (10). Current guidelines suggest that elite controllers are a subset of treatment-naïve individuals in which the benefits of therapy are unknown. That said, there is data showing that these individuals do have higher levels of immune activation and systemic inflammation than HIV-uninfected controls. This study enrolled 35 individuals with plasma HIV-1 RNA <500 copies/mL to a single arm, open-label study of rilpivirine/FTC/tenofovir disoproxil fumarate (TDF) for 48 weeks followed by the option of continuing treatment or stopping with an additional 48 weeks of follow-up. Of the enrolled individuals 37% had viral loads <40 copies/mL. The study demonstrated that the proportion with single copy HIV RNA assay reported at <6 copies/mL increased from 19 to 94% with treatment, although there was no significant effect on total HIV DNA and cell-associated HIV. From a biologic perspective, there was a significant decline in CD8+ T-cell activation and in several markers of immune exhaustion. Overall the treatment was well-tolerated and patients reported improvement in select quality of life measures. The tolerability of current medications along with improvement in select biologic measures in this study certainly support the initiation of therapy in HIV controllers. However, the true clinical benefits of such a strategy remain unknown. In addition, no data was provided on the subset with HIV viral loads <40 copies/mL at baseline, thus the benefits in this group remain unknown.
• The ANDES Study assessed the safety and efficacy of open-label ritonavir (RTV)-boosted DRV in a fixed-dose combination with 3TC compared to when combined with 3TC/TDF (11). This presentation was the Phase 1 portion of the study which included 145 treatment-naïve participants randomized 1:1 to the dual versus triple drug regimen. Prior presentations showed good responses based upon proportion with viral loads <400 copies/mL at 24 weeks. The current analysis looked at viral loads <50 copies/mL at 48 weeks showing very high rates of viral suppression for both study arms, meeting criteria for non-inferiority with 93% versus 94% suppression in the 2 versus 3 drug regimen with a difference of -1.0% (95% CI: -7.5, 5.6). Similar rates of suppression were also seen in the subset with baseline viral loads >100,000 copies/mL. Overall results showed similar rates of serious and common adverse events with good tolerability. The study is moving on to enter Phase 2 portion that will enroll an additional 190 participants to be fully powered to assess noninferiority for efficacy endpoint. Prior to this study the only contemporary, fully-powered studies to look at a tenofovir and ABC-sparing first-line regimen was LPV/r plus 3TC and DRV plus RTV plus RAL. Both of these studies had limitations with the former using a PI with inferior tolerability and the latter demonstrating reduced antiviral activity in those with high plasma HIV RNA and low CD4 cell counts. Once fully enrolled, the ANDES Study will provide data using a better tolerated more commonly used PI option.
• Study 1844 was a fully-powered randomized controlled trial of those stably suppressed on DTG/3TC/ABC who either continued current regimen or switched to BIC/FTC/TAF (12). The study enrolled 563 subjects with primary endpoint being percent with plasma HIV RNA ≥50 copies/mL at week 48. The primary outcome was 1.1 and 0.4% in those that didn't versus did switch, respectively; difference of 0.7% (95% CI: -1.0, 2.8%). In addition, 94-95% had viral loads <50 copies/mL at week 48. There was no treatment-emergent resistance, discontinuations due to adverse events and were similar changes between study arms in lipids, bone and renal parameters. This was the second switch study using this new regimen, the prior being in those on stable boosted PI-based regimen which also demonstrated noninferiority for the efficacy endpoint. This was one of the 4 registrational trials leading to the approval of this new drug for first line and maintenance therapy in virologically suppressed individuals. The DHHS guidelines were recently amended to include this option as one of the recommended initial regimens for most people with HIV.
• Study 1961 was a switch study that exclusively enrolled virologically suppressed women to continue current regimen or switch to BIC/FTC/TAF (13). This study included 470 women randomized 1:1 to continue current regimen or switch to the new treatment. The primary endpoint was once again the proportion with viral load ≥50 copies/mL at week 48 which was 2% in each arm, difference 0.0 (95% CI: -2.9, 2.9%) with 95-96% having viral loads of <50 copies/mL at this time. As seen in the previous study, there was no emergent resistance, no discontinuations due to adverse events and similar changes in lipid, bone and renal markers. Overall, this and study 1844 demonstrated that BIC/FTC/TAF is a highly effective and well-tolerated switch option for men and women who are virologically suppressed on a stable ART regimen.
• The DAWNING Study was first presented last summer after being stopped early by a data monitoring board. This was a large randomized phase III study in those experiencing virologic failure on two NRTI plus a NNRTI. A total of 624 underwent real-time drug resistance testing and were randomized to open label DTG or LPV/r plus 2 NRTI of investigators choice. Importantly, unlike earlier studies of first-line NNRTI failures where resistance testing was not routinely performed and many enrolled with extensive NRTI resistance, this study required that at least one NRTI in the regimen be fully active based upon resistance testing. At baseline, the overwhelming majority of study participants received a study regimen that included only one fully active NRTIs. At the time of an interim analysis at 24 weeks the Data Safety Monitoring Board recommended the LPV/r arm be stopped due to superior suppression of plasma HIV RNA in the DTG group.
At the time of the initial presentation there was no data presented regarding baseline drug resistance, above and beyond how many active NRTIs were in the study regimen. More data was presented at this meeting on the relationship between NRTI selection and outcomes (14). Unfortunately, this presentation once again did not include any specifics regarding the actual resistance patterns present at baseline. The current presentation assessed whether outcome was influenced by whether the NRTIs were switched to WHO recommendations or not. WHO NRTI guidelines for this setting were largely implemented in setting where resistance testing was not available and recommended that those failing a zidovudine (ZDV)-based regimen switch to one containing tenofovir, and those failing on a tenofovir-based regimen switch to one with ZDV. It was reported that approximately 60% in DAWNING followed the WHO-guidelines and that regardless of which third drug was used the outcomes were better in this group compared to those that did not follow these recommendations. The biggest difference was seen in those in the DTG arm where suppression rates in those that followed WHO guidelines versus those that did not was 87 and 78%, respectively. While interesting, the data is limited without actually knowing anything about the baseline resistance patterns. Further caution is needed in considering this data for clinical practice since it is not consistent with results observed in second-line studies, such as EARNEST where the number of active NRTIs was not related to virologic outcomes. The other important caveat is to consider how much additional efficacy is needed to justify the use of ZDV in clinical practice as increasing number of first-line failures are on tenofovir-based regimens.
• Study A5288 was an important strategy trial of third-line therapy in resource limited settings (15). This study provided real-time drug resistance testing for those failing second-line PI-based regimens. Depending upon drug resistance patterns patients were assigned different regimens. Of the 545 enrolled subjects who were INSTI-naïve and had evidence of LPV/r resistance, suppression rates of nearly 90% were observed when assigned boosted DRV plus RAL with either best available NRTIs or ETR if the latter was predicted to be susceptible. In contrast those that did not have LPV/r resistance were instructed to remain on current regimen with adherence support with <50% achieving viral suppression. This study provides guidance for those with PI resistance but does not explain what responses might have been with DRV plus RTV with RAL or best NRTIs alone. Consistent with other studies, those experiencing treatment failure with limited resistance did the worst, likely suggesting poor adherence that needs to be more aggressively addressed.
COMORBIDITY AND COINFECTION
There were many interesting presentations related to various co-morbidities and coinfections. I will focus on select data related to HIV association with atherosclerosis, the management of patients with end stage renal disease and tuberculosis coinfection.
• HIV infection, especially in non-blacks was associated with increased progression of high coronary artery plaque.
• A prospective study of CT angiography showed increased risk of noncalcified plaque in HIV-infected patients using ABC-compared to other commonly used agents.
• Reversible platelet abnormalities were observed in those on ABC-containing regimens that were switched to tenofovir-based ART.
• Preliminary data suggests that elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF may be a STR in those on hemodialysis.
• Rifampin probably can be used with twice-daily DTG, probably cannot be used with twice-daily BIC/FTC/TAF and might be an option for those taking TAF.
Study findings and interpretation:
• An analysis from the Multicenter AIDS Cohort Study (MACS) further explored the relationship between HIV infection and atherosclerosis, with particular focus on high risk non-calcified plaque and mixed plaque (16). The current study included just over 400 individuals, approximately 250 being HIV-infected, with serial non-contrast CT for coronary calcium and CT angiography; median interval of 4.5 years between images. HIV-infected men experience greater plaque volume progression than those uninfected, a finding that was true for both non-calcified and calcified plaque. Upon further analysis the difference was noted in non-black HIV-infected individuals but not those that were black. This data is consistent with others from the MACS and other cohorts demonstrating that HIV may be an independent risk factor for coronary atherosclerosis and progression of existing disease, although the explanation for racial differences needs further exploration.
• The SWISS HIV Cohort Study prospectively followed 403 individuals at least 45 years of age without documented coronary atherosclerosis or stroke and eGFR of at least 60 mL/min who underwent coronary CT angiography (17). They found that the only antiretroviral regimen with evidence for an increased risk of noncalcified or mixed plaque were those containing ABC with an odds ratio for having plaque, based upon cumulative exposure per 5 years being 1.5 (95% CI 1.1, 2.0). While this observation is consistent with other studies showing increased risk of cardiac events with ABC use, there remain other studies that have not demonstrated such a relationship. This study does provide additional evidence and is one of the first to make the assessment based upon coronary plaque as opposed to outcomes alone. It is noteworthy that the NA-ACCORD analysis was published around the time of this meeting and reported that ABC was independently associated with myocardial infarctions (18). An important limitation of these observational studies remains the inability account for all potential confounders.
• Study 1717 was a platelet subsidy performed to further identify a potential biologic explanation for how ABC may be associated with increased risk of myocardial infarctions (19). This substudy evaluated 61 individuals on ABC/3TC plus a third drug who either remained on this regimen or switched to TAF/FTC while continuing the same 3rd drug. Those who switched were found to have decrease in platelet reactivity induced by collagen with increased expression of the collagen receptor- glycoprotein VI on platelets. There was also an increase in soluble glycoprotein VI that persisted over time. The investigators concluded that in this randomized study they found an inherent platelet defect in those on ABC that was mediated through the glycoprotein VI pathway and was influenced by a switch to TAF/FTC. While this is interesting data that could be consistent with data from several observational cohorts, it is a relatively small dataset and does not necessarily link the observations with clinical outcomes.
• Study 1825 addressed the potential to use single tablet regimen of EVG/COBI/FTC/TAF in virologically suppressed patients with end stage renal disease on hemodialysis (20). The study included 55 patients and switched them from their stable regimen to the STR. The rationale for the study is that it is currently quite complicated to treat those on hemodialysis in light of the necessary dose adjustments with tenofovir, 3TC and FTC. It was proposed that despite the expected higher levels of FTC it would not be associated with increase toxicity. Similarly, since tenofovir levels are relatively low with TAF and renal toxicity is not relevant in these patients, even higher levels might not be clinically relevant. The investigators reported good viral suppression and drug levels of EVG and COBI were similar to those seen in those with normal renal function. FTC levels were nearly 6 times higher than those with normal renal function but without associated toxicity. There was the expected marked increase in tenofovir levels; however, the long-term consequences of this is not well defined in this setting. This regimen for 48 weeks was noted to be convenient, well tolerated, maintain viral suppression and be associated with high patient satisfaction. The long-term consequences of high levels of FTC and tenofovir are not yet know, but this study provides promising data that may represent an option for HIV-infected individuals on hemodialysis.
• Treating HIV in those with tuberculosis is complicated by a multiplicity of drug-drug interactions with rifampin. Treatment often includes antiretrovirals that can be used with rifampin, such as efavirenz or dose-adjusted antiretrovirals with rifabutin as an alternative to rifampin. It is currently not recommended that TAF be used with any rifamycins. A phase 1 study gave 21 healthy volunteers TAF/FTC alone, then TAF/FTC with rifampin and then TDF alone (21). Levels of plasma and intracellular tenofovir were decreased when given with rifampin. However, with TAF the intracellular levels, where drug actually works, remained higher than that seen when TDF is given without rifampin. The authors conclude that the use of rifampin with TAF is worthy of additional study. Another presentation reported data on the effect of rifampin on BIC/FTC/TAF when the latter is given twice daily to overcome the rifampin effect (22). Plasma levels of BIC were markedly reduced compared to the same drug given once-daily without rifampin. Based upon this it does not appear that twice-daily dosing of BIC is able to overcome the rifampin effect and that pending further data this regimen should not be used in this setting. In contrast to these results, PK studies suggest that twice-daily DTG can overcome the rifampin effects. The INSPIRING Study was a clinical trial looking at DTG at a dose of 50 mg twice-daily when given during TB therapy, compared to an EFV-based regimen and showed high rates of virologic suppression at week 24 in both groups, 81 vs. 89% for DTG versus EFV, respectively (23). This data is supportive of using this regimen in this setting.
CROI: INSPIRING: SAFETY AND EFFICACY OF DOLUTEGRAVIR-BASED ART IN TB/HIV COINFECTED ADULTS AT WEEK 24 - (03/05/18)
CROI: Switch to Bictegravir/F/TAF From DTG and ABC/3TC - (03/05/18)
CROI: Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Women - (03/06/18)
CROI 2018 was an excellent meeting with many important studies. I have chosen to focus on a select group of studies in the Cure, prevention, treatment and comorbidities/coinfection arena that are likely to impact the field and HIV management moving forward. I strongly encourage readers to go to http://www.croiconference.org where you can watch videos of presentations and download pdf versions of many of the poster presentations.
Conflicts: In the last year Eric Daar has received research support from Gilead, Merck, ViiV and was a consultant for Gilead, Merck, Theratechnologies and ViiV.
1. Borducchi E, Abbink P, Nkolola J, et al. PGT121 combined with GS-9620 delays viral rebound in SHIV-infected rhesus monkeys. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 73LB. http://www.croiconference.org/sessions/pgt121-combined-gs-9620-delays-viral-rebound-shiv-infected-rhesus-monkeys.
2. Thomson KA, Hughes JP, Baeten J, et al. Female HIV acquisition per sex act is elevated in late pregnancy and postpartum. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 45. http://www.croiconference.org/sessions/female-hiv-acquisition-sex-act-elevated-late-pregnancy-and-postpartum.
3. Thomson KA, Hughes J, Baeten JM, et al. Increased risk of female HIV-1 acquisition throughout pregnancy and postpartum: A prospective per-coital act analysis among women with HIV-1 infected partners. J Infect Dis 2018. [Epub ahead of print].
4. Smith DK, Van Handel M, Grey JA. By Race/ethnicity, blacks have highest number needing PrEP in the United States, 2015. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 86. http://www.croiconference.org/sessions/raceethnicity-blacks-have-highest-number-needing-prep-united-states-2015;
5. Grulich A, Guy RJ, Amin J, et al. Rapid reduction in HIV diagnoses after targeted PrEP implementation in NSW, Australia. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 88. http://www.croiconference.org/sessions/rapid-reduction-hiv-diagnoses-after-targeted-prep-implementation-nsw-australia.
6. Buchbinder SP, Cohen SE, Hecht J, et al. Getting to zero new HIV diagnoses in San Francisco: What will it take? 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 87. http://www.croiconference.org/sessions/getting-zero-new-hiv-diagnoses-san-francisco-what-will-it-take.
7. Markowitz M, Gettie A, St. Bernard L, et al. Low dose MK-8591 protects rhesus macaques against rectal SHIV infection. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 89LB. http://www.croiconference.org/sessions/low-dose-mk-8591-protects-rhesus-macaques-against-rectal-shiv-infection
8. Labhardt ND, Ringera I, Lejone TI, et al. Same day ART initiation after home-based HIV testing: A randomized controlled trial. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 94.
9. Bacon O, Chin JC, Hsu L, et al. The rapid ART program initiative for HIV diagnoses (RAPID) in San Francisco. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 93. http://www.croiconference.org/sessions/rapid-art-program-initiative-hiv-diagnoses-rapid-san-francisco.
10. Li JZ, Segal FP, Bosch R, et al. ART reduces T cell activation and immune exhaustion markers in HIV controllers. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 229. http://www.croiconference.org/sessions/art-reduces-t-cell-activation-and-immune-exhaustion-markers-hiv-controllers
11. Figueroa MI, Sued OG, Gun AM, et al. DRV/R/3TC FDC for HIV-1 treatment-naïve patients: Week 48 results of the ANDES Study. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 489. http://www.croiconference.org/sessions/drvr3tc-fdc-hiv-1-treatment-na%C3%AFve-patients-week-48-results-andes-study
12. Molina J-M, Ward D, Brar I, et al. Switch to Bictegravir/F/TAF from DTG and ABC/3TC. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 22. http://www.croiconference.org/sessions/switch-bictegravirftaf-dtg-and-abc3tc
13. Kityo C, Hagins D, Koenig E, et al. Switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in women. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 500. http://www.croiconference.org/sessions/switching-bictegraviremtracitabinetenofovir-alafenimide-bftaf-women.
14. Aboud M, Brites C, Lu H, et al. DTG versus LPV/R in second line (DAWNING): Outcomes by WHO-recommended NRTI backbone. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 508. http://www.croiconference.org/sessions/dtg-versus-lpvr-second-line-dawning-outcomes-who-recommended-nrti-backbone
15. Grinsztejn B, Hughes MD, Ritz J, et al. Results of ACTG A5288: A strategy study in RLS for 3rd-line ART candidates. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 30LB. http://www.croiconference.org/sessions/results-actg-a5288-strategy-study-rls-3rd-line-art-candidates
16. Post W, Haberlen S, Zhang L, et al. HIV infection is associated with progression of high risk coronary plaque in the MACS. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 77. http://www.croiconference.org/sessions/hiv-infection-associated-progression-high-risk-coronary-plaque-macs.
17. Kovari H, Calmy A, Doco-Lecompte T, et al. Antiretroviral drugs associated with subclinical coronary artery diseases. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 670. http://www.croiconference.org/sessions/antiretroviral-drugs-associated-subclinical-coronary-artery-disease.
18. Elion RA, Althoff KN, Zhang J, et al. Recent abacavir use increases risk for types 1 and 2 myocardial infarctions among adults with HIV. J Acquir Immune Defic 2018. [Epub ahead of print].
19. Mallon PW, Maughan RT, Garcia AA, et al. Change in soluble glycoprotein VI (SGPVI) when switching from ABC/3TC to TAF/FTC. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 677LB. http://www.croiconference.org/sessions/change-soluble-glycoprotein-vi-sgpvi-when-switching-abc3tc-tafftc
20. Eron JJ, Lelievre J-D, Kalayjian R, et al. Savety and efficacy of E/C/F/TAF in HIV-infected adults on chronic hemodialysis. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 732. http://www.croiconference.org/sessions/safety-and-efficacy-ecftaf-hiv-infected-adults-chronic-hemodialysis
21. Cerrone M, Alfarisi O, Neary M, et al. Rifampin effect on tenofovir alafenamide (TAF) plasma/intracellular pharmacokinetics. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 28LB. http://www.croiconference.org/sessions/rifampin-effect-tenofovir-alafenamide-taf-plasmaintracellular-pharmacokinetics
22. Custodio JM, West SK, Collins S, et al. Pharmacokinetics of bictegravir administered twice daily in combination with rifampin. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 34. http://www.croiconference.org/sessions/pharmacokinetics-bictegravir-administered-twice-daily-combination-rifampin
23. Dooley K, Kaplan R, Mwelase N, et al. Safety and efficacy of dolutegravir-based ART in TB/HIV coinfected adults at week 24. 25th Conference on Retroviruses and Opportunistic Infections 2018, Abstract 33. http://www.croiconference.org/sessions/safety-and-efficacy-dolutegravir-based-art-tbhiv-coinfected-adults-week-24.