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CROI Summary Report by Eric Daar, MD for NATAP
23rd Conference on Retroviruses and Opportunistic Infections
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CROI Summary Report by Eric Daar, MD for NATAP
23rd Conference on Retroviruses and Opportunistic Infections
February 22-25, 2016
Boston, Massachusetts
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 23rd Conference on Retroviruses and Opportunistic Infections (CROI) was an excellent meeting in Boston with approximately 4,000 delegates, nearly half from outside the United States and approximately 1000 oral and poster presentations on topics including but not limited to HIV pathogenesis, prevention, treatment and cure. 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."
HIV PREVENTION
After years of data focusing on the role of oral tenofovir DF (TDF) with or without emtricitabine (FTC) for pre-exposure prophylaxis (PrEP), this meeting represented a shift towards the potential of long-acting (LA) agents to address the various obstacles to adherence with daily therapy.
Headlines:
⋅ Dapivirine (a nonnucleoside reverse transcriptase inhibitor [NNRTI]) impregnated vaginal ring placed once per month was well tolerated and reduced infection in high risk women by 26-31% and up to nearly 60% when used consistently. Interestingly, two different studies showed a lack of efficacy in those 21 years or age or younger.
⋅ Intramuscular cabotegravir (an integrase strand transfer inhibitor [INSTI]) given every 3 months was reasonably well tolerated and demonstrated its potential as a LA PrEP.
⋅ The loss of bone mineral density (BMD) seen in those receiving TDF-based PrEP was reversed when such treatment was interrupted.
⋅ Maraviroc, a CCR5 antagonist given with or without other drugs showed some promise as an alternative daily PrEP regimen.
⋅ Tenofovir alafenamide (TAF) appears to have lower levels in vaginal and anal mucosa tissue than TDF.
Study findings/Interpretation:
⋅ Dapivirine is a new NNRTI that can be impregnated into a silicone ring and easily inserted and removed from the vagina. The ring slowly releases drug locally with systemic absorption. Two large studies using this product were conducted with results reported at this meeting. Both studies used dapivirine impregnated vaginal ring once monthly to reduce the risk of HIV acquisition in high risk heterosexual women. The studies MTN 020/ASPIRE (1, 2) and the Ring study (3) had similar designs and results. The MTN study enrolled just over 2600 women in Africa with approximately 99% finishing the study. Adherence was quantitatively assessed using detection of drug levels in blood and absence of drug remaining in returned rings, showing 82 and 84% adherence, respectively. Overall there were 71 incident infections in the active drug group versus 97 in the placebo arm with incidence per 100 patient years of 3.3 vs. 4.5 or a reduction of 27% (95% CI 1, 46), p=0.046. While this was a significant difference, the overall efficacy was modest with lower bound 95% CI interval being 1%. Further analyses attempted to better understand the results with a notable difference seen between those 21 years of age or younger, versus those greater than 21 years of age where for the former there was no benefit, while for the latter the reduction in risk was 56% (95% CI 31, 71), p<0.001.
The Ring study enrolled nearly 2000 women from Africa using the same product and assessments of adherence. The incidence of infection per 100 patient years was 4.1 vs. 6.1 for active drug versus placebo, respectively, with 31% reduction in risk (95% CI 1, 51). Once again there was no benefit for those 21 years or younger while those greater than 21 years had a reduced risk of 37% (95% CI 3.5, 59). Although some of the differences in response seen in the younger participants is likely related to adherence, further analyses will be needed to determine whether there were other yet unexplained reasons for this divergence. Conclusions from these studies are that we now have two confirmatory trials showing significant, albeit relatively modest benefit from a LA vaginal ring for PrEP. While we would have liked to see greater efficacy, the studies illustrate the very high rate of infection amongst these women and the importance of them having a method of protection that they completely control.
⋅ The ÉCLAIR Study assessed the safety, tolerability and acceptability of cabotegravir, a novel INSTI that has been developed in an oral and nanoformulation, the latter being for LA intramuscular administration (4). The drug is being developed as part of a LA treatment regimen and for PrEP. New data on treatment is summarized below. As for its role in PrEP there is a great deal of enthusiasm based upon animal studies showing high levels of protection. One of the challenges for use in humans will be the acceptability of relatively large volume intramuscular injections. The ÉCLAIR study dosed the oral formulation of cabotegravir (30 mg/day) on a daily basis for 4 weeks to assure there were no severe drug reactions and then randomizing participants 5:1 to cabotegravir LA (800 mg) versus saline injection every 12 weeks for 3 doses. The drug was well-tolerated with the most common adverse events being injection site reactions which occurred more frequently in the cabotegravir LA than placebo group with no participants discontinuing study due to adverse events. Most reactions were characterized as mild to moderate pain and/or swelling. Despite this being a fairly common reaction, most said that they were very satisfied with the treatment (~85%) and in fact would happily continue the injectable therapy (~90%). Modeled pharmacokinetics (PK) data suggested that adequate levels could be maintained with once every 12 week dosing, but the actual data measured in ÉCLAIR suggested that every 8 week dosing would probably be more appropriate. Conclusions from this study include that the drug will likely be given every 8 weeks in further clinical trials of this product and despite injection site reactions being common, the overwhelming majority of study participants were very content moving forward with this type of treatment.
⋅ One of the concerns about current PrEP strategies which include TDF is the frequently associated decline in BMD. A follow-up study of iPrEx which included men who have sex with men, monitored participants that stopped PrEP prior to restarting an open-label follow-up study (5). The investigators reported that there was a return in BMD to pre-therapy levels which is somewhat reassuring that when this form of PrEP is used as a bridge to a time when the patient can safely stop, the loss of BMD will be regained, perhaps placing patients at lower long term risk associated with lower bone density.
⋅ HPTN 069/ACTG 5305 explored another novel strategy for PrEP to avoid the toxicity of TDF by substituting it with maraviroc, a CCR5 antagonist that is approved for treatment of HIV infection (6). This study was designed to assess safety and enrolled nearly 400 HIV-uninfected individuals and randomized them to daily maraviroc (150 mg/day), maraviroc + FTC, Maraviroc + TDF or the standard of care TDF/FTC. The study included matched placebo so each individual received three pills per day. There were no significant drug-drug interactions observed between the drugs and relatively high level of adherence with study drug seen, with drug levels present in blood of 83% of participants. The enrolled participants continued to have high risk activities with 22% having over 100 sexually transmitted infection during follow-up. Adverse events were rare and no different between study arms; however, select adverse events such as changes in BMD are yet to be reported. Although the study was not powered to show difference in efficacy, there were 5 incident infections, 4 in the maraviroc alone group and one in the maraviroc + TDF study arm. Drug levels were performed in these cases with 3 of the 4 maraviroc alone participants having suboptimal levels. The individual on maraviroc + TDF had no detectable levels of either drug, suggesting poor adherence.
A sub study looked at mucosal markers including the ability to infect tissue explants (7). In this study less protection was seen in explants from those in the maraviroc alone group than those receiving other regimens. Conclusions from this study was that the regimens were well tolerated, recognizing that there may be additional benefits of the novel regimens when further data is analyzed, such as BMD. That said, there are some concerns regarding the explant data with maraviroc alone, acknowledging that the ability of this type of ex vivo study to predict in vivo protection has not been definitively shown.
⋅ One of the concerns about TDF-based PrEP is that it is associated with a variable decline in BMD. One strategy to overcome this is to avoid TDF, such as explored in HPTN 069/ACTG 5305, or LA formulations of NNRTIs or INSTIs. Another is to consider the potential role of the new formulation of tenofovir, TAF which has been shown to be associated with less effect on BMD and possibly enhanced renal tolerability. A phase 1 PK study was performed with TAF in 8 healthy women given one 25 mg dose of TAF with sampling of plasma, peripheral blood mononuclear cells (PBMCs), cervicovaginal fluid, as well as biopsies of cervix, vagina and rectum (8). As expected, plasma levels of tenofovir (TFV) were lower and levels in PBMCs were higher including for the active TFV diphosphate (TFVdp) than with TDF. In all mucosal tissues the TFV area under the curve ranged from 20-90% lower with TAF than TDF. In addition, TFVdp was detected in only 2 vaginal and cervical samples and on 4 rectal tissue biopsies, which is much lower than what has been seen with TDF dosing. Conclusions from this study are that TDF and TAF do behave the same and pending more data with TAF it should not be used for PrEP. That said, the path forward for studying TAF for PrEP is unclear since a standard clinical endpoint trial comparing it with TDF-based regimen would likely be prohibitively large.
ANTIRETROVIRAL THERAPY
There were several very important presentations related to the treatment of antiretroviral-naïve and experienced patients. This includes data with new drugs in existing and new classes as well as new formulations of existing drugs. Perhaps the big advance is the emergence of LA therapy.
Headlines:
⋅ Maintenance therapy with a combination of LA cabotegravir and rilpivirine is effective, reasonably well tolerated and acceptable to participants.
⋅ Switch from TDF/FTC to TAF/FTC is effective and associated with less renal and bone adverse events.
⋅ Extended analyses support the relative renal safety of TAF in those with or at risk for renal disease.
⋅ Doravirine, a new NNRTI is effective and well tolerated in early studies.
⋅ Those failing first-line NNRTI-based therapy respond equally well to lopinavir/ritonavir with nucleoside reverse transcriptase inhibitors (NRTIs) as with the INSTI raltegravir.
⋅ MK-8591 is a promising new LA NRTI.
Study findings and interpretation:
⋅ The LATTE 2 study is a phase 2 trial to assess the ability of cabotegravir LA plus rilpivirine LA given as intramuscular injections to maintain viral suppression (9). The study enrolled approximately 300 treatment naïve participants who were initiated on abacavir/lamivudine plus oral cabotegravir (30 mg/day) for 20 weeks. Those virologically suppressed had oral rilpivirine added for four weeks to assure tolerability and then if still suppressed, which was the case for the overwhelming majority, they were randomized 2:2:1 to either every month or every two month injections of cabotegravir LA (400 or 600 mg) and rilpivirine LA (600 or 900 mg) or continued abacavir/lamivudine + oral cabotegravir as a control. The LA drugs were given at the once monthly and every two month intervals as either two 2-mL or two 3-mL intragluteal injections, respectively. After 32 weeks of follow-up on LA therapy plasma HIV RNA levels were less than 50 copies/mL in greater than 90% in all groups with only 2 protocol-defined virologic failures. There were no major adverse events noted other than injection site reactions, mostly being pain that lasted only a few days and became less frequent with time. Despite the frequent injection site reactions only two individuals withdrew and nearly 100% of individuals in both LA study groups were satisfied with treatment and willing to continue if asked. A PK study was performed and suggested that both the monthly and every two month dosing schedule maintained therapeutic levels. The conclusion from this study is that the LA preparations were highly effective in maintaining viral suppression and despite frequent injection site reactions were considered very acceptable options by the study participants. As a result of this study a phase 3 protocol is being planned.
⋅ The results of GS 1089, a TAF/FTC switch study was reported at this meeting (10). TAF is a novel formulation of tenofovir that is given as a very small dose, 10 or 25 mg per day depending upon whether it is given with a boosted protease inhibitor or not. TAF results in lower levels of drug in plasma with higher concentration in lymphoid cells and was recently approved as part of the single tablet regimen of elvitegravir/cobicistat/emtricitabine/TAF which proved to be as effective and with enhanced renal and bone tolerability compared to the previously approved TDF-containing regimen. In fact, in the United States it was rolled out at no additional cost compared to the previously approved therapy and was approved for those with creatinine clearance (CrCl) of down to 30 mL/minute, unlike the equivalent TDF-based regimen which is approved for those with CrCl down to 70 mL/minute. Although another study with single tablet rilpivirine/FTC/TAF has not yet been reported, it was submitted to the FDA and approved on March 1, 2016.
GS 1089 is the registrational trial for FTC/TAF. The study enrolled 663 virologically suppressed individuals on a TDF/FTC-based regimen with CrCl of at least 50 mL/minute and randomized them 1:1 to continue their current medications or switch TDF/FTC to TAF/FTC. The primary endpoint was viral suppression at 48 weeks with planned follow-up to 96 weeks. Approximately half of the participants were on a boosted protease inhibitor and the other half not with suppression rates at 48 weeks being 93-94% with a difference of 1.3% (95% CI -2.5, 5.1), meeting noninferiority criteria. There was no difference in response based upon age, sex, race or which third drug was used and only one individual experienced virologic failure with resistance. The adverse event profile was as expected based upon other TAF studies with a more favorable effect on change in CrCl, although modest and of unknown clinical benefit, as well as less proteinuria and renal tubular proteinuria. The BMD data was also compelling, remaining stable in those randomized to continue their current regimen and increased by 1.1 and 1.5% in the TAF arm at the spine and hip, respectively. The conclusion from this study is that TAF/FTC is a viable substitute for TDF/FTC and has a more favorable effect on bone density and a variety of renal parameters. The fixed dose combination of TAF/FTC is under FDA review and expected to be approved in April of 2016.
⋅ Most studies have demonstrated that TAF is associated with more favorable change in CrCl and in overall proteinuria and specifically renal tubular proteinuria than TDF. This along with a single arm study of TAF used in those with CrCl between 30 and 60 mL/minute led to the approval of the first TAF-containing combination pill, elvitegravir/cobicistat/emtricitabine/TAF for those with CrCl as low as 30 mL/minute. The limitations of short term studies and the fact that the study of those with advanced kidney disease did not have a control arm will require that further analyses to confirm the overall safety of TAF in those with renal dysfunction. At this meeting there were three analyses presented that attempted to address this issue using follow-up data from a variety of existing studies, focusing on the subset of individuals enrolled with underlying renal disease (11-13). All three posters showed that TAF appears to be safe in these participants. The conclusion from these studies is that TAF appears to have a relatively good renal safety profile, including in those with underlying renal disease. Recognizing that the full extent of TDF renal toxicity became most evident with longer-term follow-up, it is hoped that further analyses will continue to assess the renal safety of TAF over time, with a particular focus on those with advanced renal disease.
⋅ Doravirine is a new NNRTI in development that is anticipated to be at least as effective as, and better tolerated than efavirenz. Results of a phase 2 study were reported at this meeting where after a dose-finding study established the 100 mg dose as the one to move forward with, compared doravirine to efavirenz when combined with TDF/FTC (14). The study enrolled 216 participants with the rate of virologic suppression for doravirine (77.8%) and EFV (78.7%)-based regimens being very good and similar. Adverse events favored doravirine with notably less central nervous system toxicity and less of an effect on lipids than EFV. The conclusion from this study is that doravirine does appear to be effective and tolerable at a dose of 100 mg/day and this supports the rationale for the ongoing phase 3 trial.
⋅ ACTG5273 is the third study conducted in resource limited setting to assess the safety and efficacy of switching those failing first-line NNRTI-based regimens to lopinavir/ritonavir with either NRTIs or raltegravir (15). The previous studies addressing this issue were SECOND LINE and EARNEST which showed that the raltegravir-based regimen performed as well as the NRTIs when used with lopinavir/ritonavir. A5273 randomized over 500 participants who like the other studies did not have access to routine plasma HIV RNA or resistance testing so that virologic failure was often identified late and after there was already accrual of considerable NNRTI and NRTI resistance. The study enrolled participants from India, Malawi, South Africa, Zimbabwe, Kenya, Tanzania Peru, Thailand and Brazil. The median follow-up was 87 weeks with the primary endpoint being time to virologic failure which showed a difference of -3.4% (95% CI -8.4, 2.5), confirming noninferiority of raltegravir to NRTI-based regimens. The proportion with plasma HIV RNA <400 copies/mL was approximately 90% at 48 weeks in both groups with time to tolerability endpoint being shorter for NRTIs than RAL. Additional analyses showed that in the NRTI arm the response rates remained high even in those who had substantial NRTI resistance, including multiple thymidine analogue mutations or K65R. As seen in the previous studies, those with the most underlying resistance at the time of entering the study had the best virologic response, an observation that suggests that the amount of resistance is a surrogate for adherence. The conclusion from this study is that it confirms others that have influenced guidelines both for how to manage first-line NNRTI-based regimen failures. It also illustrates the potency of boosted protease inhibitors in any setting where they can be combined with a new drug, such as an INSTI, or even recycled NRTIs.
⋅ Very early data was presented with a novel NRTI, MK-8591, known as EFdA which inhibits reverse transcriptase by preventing translocation. Preliminary data presented at this meeting showed that a single 10 mg oral dose reduced plasma HIV RNA by 1.6 log10 copies/mL by 7-10 days. In addition, the pharmacokinetics of a parenteral formulation demonstrated therapeutic levels in an animal model in excess of 180 days (16). The conclusion from the presented data is that this novel drug may represent another LA option with potential for both HIV therapy and prevention.
LINKAGE AND RETENTION IN CARE
Despite the availability of increasingly effective, tolerable and easy to take regimens there remains a large number of individuals that do not engage in care and maintain virologic suppression. In fact, in the United States it is estimated that only approximately 30% of HIV-infected individuals have suppressed plasma HIV RNA despite widely available care and treatment. Although there are many reasons why so many fail to take advantage of available treatments, one very high risk group remain those dealing with substance abuse. One of the largest study to target this population was reported at CROI.
Headline:
⋅ An intensive intervention using patient navigators with or without cash payment (contingency management) in hospitalized substance abusing participants resulted in improved engagement in care and viral suppression at 6 months that was no longer present at the time of the primary endpoint of 12 months.
Study findings and interpretation:
The HOPE Study was an ambitious attempt to engage in care a very high risk patient population defined as those admitted to the hospital with detectable plasma HIV RNA who engage in substance or alcohol abuse (17). The study enrolled 801 participants at 11 different hospitals across the United States. Inclusion criteria was being admitted to a hospital, having detectable plasma HIV RNA and CD4 cell count <500 cells/uL as well as opioid, stimulant and/or alcohol abuse. Participants were randomized them 1:1:1 to treatment as usual, a patient navigator or a patient navigator with financial incentives. The patient navigator intervention included up to 11 sessions to engage the participants in care as well as assisting them with attendance of medical and substance abuse treatment appointments. For the financial incentive group participants were paid up to $1160 if they attended all visits and met a variety of other objectives. The interventions were all limited to the first 6 months and the primary endpoint of the study was viral suppression after 12 months. There were multiple secondary endpoints including but not limited to viral suppression at 6 months and engagement in care at both 6 and 12 months. There was no difference between any of the arms for the primary endpoint with viral suppression being 34-39%, p=0,68. Although there were some advantages between the intervention arms and treatment as usual at six months for viral suppression, ranging from 34-46%, p=0.04, and engagement in care, these benefits that were lost by the 12 month visit. Conclusions from this study include that the benefits observed were lost after the interventions were stopped at 6 months. The study further shows how difficult it will be to engage some of the most challenging patient populations and the critical need to address obstacles to care amongst substance abusing individuals.
HPV VACCINATION
There is clear evidence supporting the use of the quadrivalent HPV vaccine in HIV-infected and uninfected individuals up to 26 years of age. A common question is whether there would be any benefit for those older.
Headline:
⋅ The quadrivalent HPV vaccine was highly immunogenic in healthy HIV-infected individuals more than 26 years of age but there was no evidence that this was associated with any clinical benefits.
Study findings and interpretation:
The quadrivalent HPV vaccine immunizes against HPV 6, 11, 16 and 18 and has been shown to be beneficial and is currently approved for use in those up to 26 years of age. ACTG 5298 was designed to determine whether older HIV-infected individuals would derive benefit from immunization with this product (18). The study randomized participants greater than 26 years of age without history of HPV malignancy and who engage in receptive anal intercourse, stratifying by sex and presence or absence of high grade intraepithelial lesions (HSIL). Participants were dosed at week 0, 8 and 24 with active vaccine or placebo and followed with serology, as well as cytology and HPV testing of anal and oral specimens. Follow-up was to be for 3-4 years with the primary endpoint being the development of persistent HPV infection that was not present at baseline. In September 2015 the Data Safety Monitoring Board stopped the study due to futility, i.e. the inability for the study to demonstrate a difference between study groups.
At baseline 33% had anal HSIL, 64% abnormal cytology and 60% with anal infection by at least one of the HPV serotypes included in the vaccine. The vaccine was well tolerated and highly immunogenic with seroprevalence to HPV 16 going from ~50% at baseline to 99.6% at week 28. Outcomes of persistent new HPV infection (detected on two consecutive visits), or presence at the last study visit was detected in 26 versus 33 individuals for the vaccine and placebo group, respectively, HR 0.75 (95% CI 0.45, 1.26), which was not significant. There was similarly no difference when only including those with persistent infection or for the development of HSIL at week 52 or later. It was noted that persistent new oral HPV infection occurred in 1 versus 8 in the vaccine and placebo, p=0.019, respectively. Conclusions from this study are that that although safe and highly immunogenic, the findings do not support the routine use of quadrivalent vaccine in HIV-infected individuals more than 26 years of age. The intriguing data with oral HPV infection represents small numbers and may be worthy of further study in the future.
CONCLUSIONS
Another great CROI with exciting new data on topics ranging from pathogenesis, cure, viral hepatitis, tuberculosis. Since I could not begin to discuss the many outstanding presentations I strongly encourage people to go to the CROI website (www.croiconference.org/) where they can review many of the presentations as well as see abstracts and posters.
Conflicts: In the last year Eric Daar has received research support from Bristol Myers Squibb, Gilead, Merck, ViiV and was a consultant for Abbvie, Bristol Myers Squibb, Gilead, Merck, Teva and ViiV.
REFERENCES
1. Baeten JM, Palanee-Phillips T, Brown ER, et al. A phase III trial of dapivirine vaginal ring for HIV-1 prevention in women. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 109LB.
2. Baeten JM, Palanee-Phillips T, Brown ER, et al. Use of a Vaginal ring containing dapivirine for HIV-1 prevention in women. NEJM 2016 [Epub ahead of print].
3. Nel Am Kapiga S, Bekker S-G, et al. Safety and efficacy of dapivirine vaginal ring for HIV-1 prevention in African women. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 110LB.
4. Markowitz M, Frank I, Grant R, et al. ÉCLAIR: Phase 2A safety ad PI study of cabotegravir LA in HIV-uninfected men. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 106.
5. Grant R Mulligan K, McMahan V, et al. for the iPrEx study team. Recovery of bone mineral density after stopping oral HIV preexposure prophylaxis. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 48LB.
6. Gulick R, Wilkin TJ, Chen Y, et al. HPTN 069/ACTG 5305: phase II study of maraviroc-based regimens for HIV PrEP in MSM. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 103.
7. McGowan I, Nikiforov A, Young A, et al. PrEP implant on T cell activation and explant infection: HPTN 069/ACTG 5305 substudy. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 104.
8. Garrett KL, Cottrell ML, Prince HM, et al. Concentrations of TFV and TFVdp in female mucosal tissues after a single dose of TAF. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 102LB.
9. Margolis DA, Gonzalez-Garcia J, Stellbrink H-J, et al. Cabotegravir + rilpivirine as patient-acting maintenance therapy: LATTE-2 week 32 results. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 31LB.
10. Gallant JE, Daar E, Raffi F, et al. Switching tenofovir DF to tenofovir alafenamide in virologically suppressed adults. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 29.
11. Post FA, Tebas P, Clarke A, et al. Longer-term safety f tenofovir alafenamide in renal impairment. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 680.
12. Wohl D, Thalme A, Finlayson R, et al. Renal safety of tenofovir alafenamide in patients at high risk of kidney disease. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 681.
13. Rijnders BJ, Post FA, Rieger A, et al. Longer-term renal safety of tenofovir alafenamide vs tenofovir disoproxil fumarate. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 682.
14. Gatel JM, Raffi F, Plettenberg A, et al. Doravirine 100 mg qd vs efavirenz + TDF/FTC in ART-naïve HIV+ patients: Week 48 results. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 470.
15. La Rosa AM, Harrison LJ, Taiwo B, et al. ACTG 5273 randomized trial of second-line ART supports WHO guidance. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 30.
16. Grobler J, Friedman E, Barrett SE, et al. Long-acting oral and parenteral dosing of MK-8591 for HIV treatment or prophylaxis. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 98.
17. Metsch L, Feaster D, Gooden L, et al. A patient navigation/contingency management RCT for hospitalized HIV+ substance users. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 27.
18. Wilkin TJ, Chen H, Cespedes M, et al for the ACTG A5298 Team. ACTG A5298: A phase 3 trial of the quadrivalent HPV vaccine in older HIV+ adults. 23rd Conference on Retroviruses and Opportunistic Infection 2016, Boston, MA, Abstract 161.
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