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21st International AIDS Conference
July 18-22, 2016
Durban, South Africa
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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 21st International AIDS Conference represented the third such meeting in Africa and the return to Durban after the first meeting occurred 16 years ago. There were many presentations on topics ranging from epidemiology, prevention, treatment, implementation science and beyond. Prior to talking about specific studies it is worth noting that there was a substantial amount of attention given to the successes since the previous meeting in Durban as well as potential concerns moving forward. A particular focus was on the impact the roll out of antiretroviral therapy (ART) has had on the global pandemic. As of 2015 there are estimated to be nearly 37 million people living with HIV compared to just over 33 million in 2010. In addition, there were 1.1 million who died of AIDS in 2015, representing a 45% decrease since 2005. While this was good news, it was reported that there has been no real decline in new infection in past 5 years, remaining at just over 2 million per year as of 2015, approximately 5700 per day. That said, there has been a decline in new HIV infections among children, a more than 70% decline since 2001. No doubt, much of the positive data reflects the dramatic roll out of ART since 2000 with nearly 50% of people living with HIV now on treatment with an estimated 40% being virologically suppressed. This expansion of therapy has been further noted amongst pregnant women and children where in 2015 approximately 75% of the former were estimated to be on treatment for prevention of vertical transmission and 50% of the latter on ART for their own health.
There were many studies presented at the meeting which makes it very difficult to pick which to discuss. I will pick those related to key topics that I think are of interest to clinicians as well as a study using a new regimen for treatment of HCV in HIV/HCV co-infected individuals. I will provide summaries that include what I considered the "headlines" followed by "study findings/Interpretation."
HIV PREVENTION
A major focus at this meeting was the use of pre-exposure prophylaxis (PrEP) and treatment of HIV infected to prevent transmission to their uninfected partners. In addition, there was an overview of the vaccine effort with some new data defining a path forward.
Headlines:
⋅ "The HIV vaccine field is open for business," as stated in a plenary by Larry Corey the Principal Investigator of the National Institute of Allergy and Infectious Diseases (NIAID)-supported HIV Vaccine Trials Network (HVTN).
⋅ Follow-up data presented for on-demand PrEP from the IPERGAY study showed continued low risk of HIV acquisition, although limited by the frequent use of PrEP due to repeated sexual exposures. There was also continued concerns regarding the high frequency of sexually transmitted infections (STIs).
⋅ Follow-up analysis from ASPIRE study of Dapivirine (a nonnucleoside reverse transcriptase inhibitor [NNRTI]) impregnated vaginal ring placed once per month which showed efficacy could exceed 75% in those with optimal adherence.
⋅ PrEP use in the United States on the rise with over 700% increase between early 2013 and end of 2015.
⋅ Treatment of HIV-infected individuals engaging in condomless sex with uninfected partners (PARTNERS study) continues to demonstrate ZERO within partner transmission events, including in high risk men who have sex with men (MSM).
⋅ In serodiscordant couples the risk of transmission is very low if the uninfected person uses PrEP during the first 6 months that the infected partner initiates ART (PARTNER Demonstration Project).
Study findings/Interpretation:
⋅ HIV Vaccine plenary and "Go" Study. Larry Corey, Principal Investigator of NIAID-supported HVTN provided a plenary on current status of the vaccine program. He provided an overview of the importance of identifying a vaccine in light of the approximately 45,000 new cases of HIV infection per year in the United States and over 2 million globally. He noted that there are many strategies being pursued to address new infections but that vaccines have been key for curbing the spread of most infectious diseases. He provided a summary of the disappointing efficacy trials conducted to date with a small glimmer of hope from the RV144 Thai Trial using ALVAC/gp120 where there was some efficacy noted, although benefits were modest and waned with time. This hint of success was followed by an intensive effort to define potential correlates of protection. Without going into details the results found immunologic correlates that were not previously thought relevant but felt to provide guidance for how to decide which future vaccine candidate to move forward. This resulted in pursuing related compounds with a plan to proceed with those that met all of the immunologic correlates of protection identified in RV144 (1).
A phase 1/2 study using clade C ALVAC and bivalent subtype C gp120 in HIV-uninfected South African adults did indeed meet this "Go" criteria (2), and will be pursued in a phase 3 trial, HVTN 702 which is to be initiated within the next 6 months in South Africa. Two other efficacy studies were described, one using a multi-clade approach and another using broadly neutralizing antibodies that will be initiated over the next year.
⋅ "On Demand" PrEP in ANRS IPERGAY open-label extension. The primary results of PERGAY was previously reported and published demonstrating that in high-risk MSM two doses of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 2-24 hours before sex and a single tablet at 24 and 48 hours after sex markedly reduced the risk of acquiring HIV infection (86% relative reduction compared to placebo). In fact, the efficacy was so great that the study was stopped prematurely. An open-label extension study was designed in order to continue to follow individuals using this strategy (3). At this meeting the results were presented from the open-label extension. The incidence of infection per 100 patient years of follow-up during the open-label phase with 515 patient years of follow-up was 0.19 (95% CI 0.01-1.08) compared to 6.60 in the placebo treated and 0.91 in the blinded TDF/FTC group. There was a single HIV infection during the open-label phase in a person who was reported to have not used PrEP for months, had no detectable drug levels at time of HIV diagnosis, and had no drug resistance mutations identified. Much like what was seen in the primary results, the median number of pills taken per month was 18 due to the frequent sexual exposures. This frequent dosing limits the ability to define how effective this strategy truly is for those who are dosing around less frequent sexual exposures. Moreover, it is important to note that this study did not include heterosexual men or women and therefore cannot be extrapolated to these populations. Finally, STIs were noted in 58% of patient during open-label phase.
⋅ PrEP use in United States was assessed using national, electronic, patient-level data collected from 80% of United States retail pharmacies dispensing TDF/FTC between Jan 2012 and December 2015 (4). They used an algorithm to distinguish those getting drug for PrEP versus treatment, such as excluding those receiving concomitant other antiretrovirals or having prior diagnosis of HIV infection or opportunistic infections. They also excluded those with chronic hepatitis B. The study reported that 79,684 unique individuals started TDF/FTC for PrEP with an increase from 1671 at end of 2012 to 14,000 in last quarter of 2015, a 738% increase. It was further reported that 75% of PrEP use was in men. In addition, 28% of women were <25 years of age compared to only 11% of men getting PrEP with Massachusetts, New York and Illinois having highest rates per population and 50% of all PrEP use being in California, New York, Texas, Florida and Illinois.
⋅ ASPIRE Study of Dapivirine ring.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. MTN 020/ASPIRE 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 the decline in the amount of drug remaining in the 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. The current analysis looked at how the amount of drug remaining in returned rings over the preceding months predicted protection in order to get a better sense of the potential efficacy in an idealized situation. For those with the highest tertile of adherence during the three months prior to detection of infection by this metric there was just 1 infection with incidence per 100 patient years of follow-up of 0.4 compared to 4.7 for placebo with over 90% risk reduction (5). While this type of data has numerous limitations it certainly provides some insight into the potential utility of this strategy. Regardless, more data is needed to better understand why women were not more adherent with this potentially promising prevention strategy.
⋅ Follow-up data was presented from the PARTNER Study that followed over 800 virologically suppressed individuals who routinely engaged in condomless sex with their stable HIV-uninfected partner. The initial analysis was recently published in JAMA showing no phylogenetically-linked transmissions (6). This study provides very important new data on the risk of transmission from virologically suppressed individuals to their stable partner. Unlike in HPTN 052 which demonstrated efficacy of this strategy, this cohort included those who admitted to not using condoms and a variety of risk groups, including MSM. Limitations of the original study was that despite the lack of transmission events the confidence intervals were variable especially for MSM, and particularly for high risk MSM admitting to unprotected receptive intercourse with ejaculation due to relatively small number of subjects and follow-up (7). This study expanded the follow-up including more than 22,000 condomless sex acts among MSM (8). As in previous analyses there remained no phylogenetically-linked transmission events, now including 415 couple years of anal sex, with 137 couple-years of follow-up for those admitting to receptive intercourse with ejaculation. It was further reported that additional follow-up in MSM is ongoing through 2018 to provide a more precise estimate of risk which is critically important to inform policy and individuals in making choices. While this data along with that from other cohorts and HPTN 052 continues to be extremely promising, the data has some limitations which prevents extrapolating to all couples. This includes fact that these couples had been together for a median of 2 years at time of enrollment and had been virologically suppressed a median of approximately 7 years at entry into study. It is also worth noting that STIs were frequent and there were transmission events from nonstable partners, i.e. non-phylogenetically linked infections. Despite the limitations this is important information and the extended follow-up in MSM will be invaluable in helping couples make decisions regarding their sexual practices.
⋅ Partners Demonstration Project provided final results of the study that assessed a strategy of using PrEP and ART to prevent HIV transmission in African HIV serodiscordant couples. This study assesses a strategy for serodiscordant couples where the infected partner is just starting ART, recognizing that there is likely to be some time before the partner will be at lower risk for acquiring HIV. This was an open-label, prospective interventional study. PrEP was used until the partner was on ART for 6 months and then stopped with continued follow-up for incident infections. The study included 1013 couples with 33% of the HIV-uninfected partners being women (9). Overall there were only 4 infections, an incidence of 0.2 per 100 patient years of follow-up. Of the 4 transmissions, none used PrEP or ART and no drug resistance was noted in the newly infected partner. This study provides guidance as to how serodiscordant couples can approach PrEP and ART for prevention, recognizing it is a demonstration project with no control group.
ANTIRETROVIRAL THERAPY
There were several very important presentations related to the treatment of ART-naïve and experienced patients. This includes data with new drugs in existing and new classes as well as new formulations of currently approved drugs.
Headlines:
⋅ The ARIA Study demonstrated that dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) was superior to ritonavir-boosted atazanavir (ATV/r) plus TDF/FTC in treatment naïve women.
⋅ The ONCEMRK Study demonstrated that once-daily raltegravir (RAL) given as two 600 mg tablets once daily was well tolerated and non-inferior in efficacy to standard RAL given at 400 mg twice daily dosing with TDF/FTC in treatment-naïve individuals.
⋅ The PADDLE Trial provides pilot data showing the efficacy of a novel DTG plus 3TC regimen in ART-naïve patients.
⋅ The STRIIVING Study demonstrated that virologically suppressed individuals can be safely switched to DTG/ABC/3TC with good tolerance and maintenance of virologic suppression.
⋅ LATTE-2 shows that maintenance therapy with a combination of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) is effective, reasonably well tolerated and acceptable to participants through week 48 of follow-up.
Study findings and interpretation:
⋅ The ARIA Study enrolled ART-naïve women and randomized them to receive DTG/ABC/3TC or ATV/r + TDF/FTC (10). This represents one of several recent studies that have made a concerted effort to define the role of first-line options in women, a group often underrepresented in registrational trials. The study randomized 495 women 1:1 to each regimen with the primary endpoint being HIV RNA <50 copies/mL at 48 weeks by Snapshot algorithm. There were 5% more individuals in the DTG/ABC/3TC than ATV/r + TDF/FTC arm that completed week 48 (83 vs. 78%, respectively) with the biggest difference being those who left study because of adverse events (4 vs. 7%). The study population overall had early stage disease but 27-28% did have plasma HIV RNA >100,000 copies/mL. The primary endpoint showed virologic success in 82 vs. 71%, favoring DTG/ABC/3TC over ATV/r + TDF/FTC, a difference of 10.5% (95% CI 3.1, 17.8) showing superiority (p=0.005). The difference was primarily driven by those categorized as virologic non-response, 6 vs. 14%. The difference in response rates were also seen in those with HIV RNA ≤100,000 copies/ml (83 vs 74%) and >100,000 copies/mL (80 vs. 64%). Resistance analysis was performed on those with confirmed virologic failure with plasma HIV RNA ≥400 copies/ml on or after 24 weeks with no resistance observed in the 6 patents studied on DTG/ABC/3TC and one of four patients studied on the ATV/r + TDF/FTC arm who had the M184V mutation. Adverse events were similar with the exception of ocular icterus and jaundice in the ATV/r group with slightly higher discontinuations due to AEs in the ATV/r + TDF/FTC than the DTG/ABC/3TC groups.
⋅ ONCEMRK Study evaluated a new formulation of RAL given as two 600 mg tablets once-daily versus the currently approved 400 mg twice daily dosing (11). This was a phase 3, double-bind (double-dummy) study that randomized 797 ART-naïve individuals 2:1 to RAL 1200 daily versus RAL 400 mg twice-daily, both combined with TDF/FTC. The study included nearly 30% of patients with baseline plasma HIV RNA >100,000 copies/mL and approximately 85% being men. The rate of virologic suppression with plasma HIV RNA <40 copies/mL was virtually identical at 88-89% in both study arms with difference of 0.5 (9% CI -4.2, 5.2), meeting criteria for noninferiority. There was similarly no difference in the subgroup with plasma HIV RNA >100,000 copies/mL. It was further noted that there were no apparent differences in the frequency of adverse events between the groups. This study demonstrates that a new formulation of RAL is a safe and effective alternative to the currently approved twice-daily dose, providing a potentially new and convenient option for ART-naïve patients.
⋅ The PADDLE Trial was a pilot study to assess the activity of a novel two-drug regimen in ART-naïve individuals with relatively low plasma HIV RNA levels (12). Preferred options continue to include two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third drug. The potential of two-drug regimens can result in novel combinations that could be convenient, well-tolerated and potentially have a lower cost. This pilot study attempted to assess whether DTG plus 3TC might be a viable option which could eliminate the need for ABC, TDF or tenofovir alafenamide (TAF). Since this is a novel regimen the study took a deliberate approach of enrolling in an open-label, single arm study design 10 patients and if there was a good response to expand this to 10 more. The study also limited enrollment to those with screening plasma HIV RNA ≤100,000 copies/mL and CD4 ≥200 cells/uL. Since there is only one hepatitis B virus (HBV) active drug they excluded those with chronic HBV infection. The study group was all male except one with median HIV RNA of 24,000 copies/mL and CD4 of 507 cells/uL. The data demonstrated that all patients had plasma HIV RNA <50 copies/mL by week 8 with all but two being <50 at week 48. One of the "failures" committed suicide between week 24 and 36 due to a reportedly stressful life event. The other patient had protocol-defined virologic failure with viral load increase from <50 at week 24 to 99, then 246 and then 61 copies/mL prior to being <50 copies at week 48. No reverse transcriptase mutations were detected when viral load was 246 but the integrase region did not amplify and could not be assessed. These results are promising but limited by small sample size and selective inclusion of those with relatively low plasma HIV RNA and high CD4 cell counts. Larger studies including those with higher viral load are being pursued with a plan for fully-powered phase 3 study using this novel combination.
⋅ The STRIIVING Study was designed to see whether virologically suppressed patients can safely be switched to DTG/ABC/3TC (13). When new drugs become available questions often emerge as to whether suppressed patients can safely be switched. This was a fully powered study with primary endpoint of plasma HIV RNA <50 copies/mL at week 24 by Snapshot algorithm. Eligible patients had to be on a stable regimen and have confirmed plasma HIV RNA <50 copies/mL and be HLA-B*5701 negative. The study included 553 patients randomized 1:1 with 85% of those randomized to switch and 88% that remained on stable regimen being suppressed at 24 weeks with virtually all of the "failures" having no virologic data available at week 24. There were no protocol defined virologic failures, defined as RNA ≥400 copies/mL on consecutive assessments. There were 3 who had plasma HIV RNA levels ≥50 copies/mL at week 24, all with low level viremia and who re-suppressed without change in the regimen. Adverse events included nausea, diarrhea, fatigue, headache, insomnia, dizziness and abnormal dreams. This study provides another large data set that can be used in discussing with virologically suppressed patients whether they can safely consider switching to alternative regimens for any one of a variety of reasons.
⋅ The LATTE 2 study is a phase 2 trial to assess the ability of CAB LA plus RPV LA given as intramuscular injections to maintain viral suppression (14). The study enrolled approximately 300 ART-naïve participants who were initiated on ABC/3TC plus oral CAB (30 mg/day) for 20 weeks. Those virologically suppressed had oral RPV 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 one or every two month injections of CAB LA (400 or 600 mg) and RPV LA (600 or 900 mg), or continued on ABC/3TC + oral CAB 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 48 weeks of follow-up on LA therapy plasma HIV RNA levels were less than 50 copies/mL in greater than 89% in all groups with 2 protocol-defined virologic failures in the Q8 week dosing regimen and 1 in the oral CAB regimen. Amongst the 2 LA failures one had the Q148R integrase mutation and several NNRTI mutations. Adverse reactions were fairly similar with the exceptions of injection site reactions (ISRs) in the injectable groups. Of the ISRs 82% were defined as mild, 17% moderate and 90% were reported to resolve within 7 days. Only 2 of 230 receiving injections withdrew as a result of ISRs.
A qualitative assessment of patient acceptability was also collected asking patients how satisfied they were with their current treatment and how satisfied they would be to continue their present form of treatment. Amongst those receiving injections 79-83% said they were very satisfied with their current treatment and 85-88% said they would be very satisfied to continue their current regimen. Based upon the results of this study it appears that the LA preparations were highly effective in maintaining viral suppression and despite frequent ISRs were considered a very acceptable option by the study participants. It was reported that at least in part because there were less cases of virologic non-response with monthly than every other month dosing that the phase 3 study soon to begin will dose the drugs monthly.
CURE RESEARCH
There continues to be a substantial investment in developing an approach to curing HIV or at least completely controlling it off of ART. The focus of research continues to be on potential latency-reversing agents to stimulate viral replication from the latently infected cells that represent a measurable reservoir of infection. It is further understood that a cure may also require host immune responses to clear these latently infected cells. It has been suggested that ideal population to study novel cure therapeutic interventions might be those treated during acute infection where the reservoir may relatively small and perhaps there are preserved HIV-specific immune responses. What has also been learned from current studies is that even the most sensitive virologic assays are not capable of determining who will be able to control virus off ART. In fact, there are notable examples of HIV-infected patients who underwent stem cell transplants and the Mississippi Baby/Child that was treated early, both of whom had little or no detectable virus by very sensitive methods only to experience delayed viral rebound (15).
Headline:
⋅ The SEARCH 19 Trial studied 15 patients treated with suppressive ART during early stages of acute infection (Fiebig 3 and 4). Some received ART with vorinostat, hydroxychloroquine and maraviroc and others continued ART alone with all ultimately undergoing a treatment interruption with no difference in the time to viral rebound between the groups.
Study findings and interpretation:
⋅ The SEARCH 19 Trial studied 15 patients treated during first weeks of acute HIV infection (Fiebig III/IV) who were on suppressive ART for at least 2 years and likely to have a relatively small reservoir size (16). Ten were given three cycles of vorinostat (V) 400 mg/d (14 days on and 14 days off) as a latency reversing agent, hydroxychloroquine (H) 200 mg twice-daily as an immunomodulating agent, and maraviroc (M) an entry inhibitor at a dose of 600 mg twice-daily, with this study group referred to as ART + VHM. Five other patients were used as controls and simply remained on ART alone. The primary objective was to look at time to viral rebound after treatment interruption. Two participants had serious adverse events in the VHM group. During the treatment interruptions there were no episodes of acute retroviral syndrome, new resistance mutations emerging and all participants re-suppressed upon reinitiation of therapy. However, the median time to first viral load detection was 22 days (range 14-77) with the one with the longest time to rebound being in the ART alone group with no obvious difference in time to rebound in the VHM + ART versus ART alone participants. In addition, there was no change in total HIV DNA in peripheral blood mononuclear cells between groups despite the fact that there was evidence of low level viremia emerging in those on the VHM regimen. This carefully designed proof-of-concept study of VHM + ART in those who initiated ART during acute infection showed that such treatment is not without risk and despite the fact that it does stimulate viral release it was not associated with decline in total cellular DNA (i.e. reservoir) or time to viral rebound. The study illustrates that further research is needed to define the optimal study population for such research, which novel agents can significantly reduce the viral reservoir and the potential role for enhancing immune responses to target activated HIV-infected cells when using latency reversing agents.
HCV/HIV COINFECTION
The rapid development of direct acting agents for treatment of HCV has led to unprecedented advances in treatment with multiple options now available which achieve very high cure rates. One of the most recently approved options is sofosbuvir, a potent pan genotypic nucleoside inhibitor combined in a single tablet with velpatasvir, a second generation pan genotypic NS5A inhibitor. Recent studies demonstrated good tolerability with greater than 90% cure rates for HCV monoinfected patients with HCV genotype 1-6 virus. At this meeting data was presented from a large trial of HIV/HCV co-infected patients for both efficacy and other analyses of drug-drug interactions (DDIs) with antiretroviral agents.
Headline:
⋅ ASTRAL-5 showed that Sofosbuvir/Velpatasvir (SOF/VEL) was well tolerated with ≥95% cure rates in HIV/HCV co-infected patients on a wide range of antiretroviral agents and that these cure rates were consistent across genotypes 1 through 4, in those with and without cirrhosis, as well as treatment naïve and experienced. There also were no meaningful DDIs with the antiretrovirals studied except for efavirenz (EFV) which should not be used.
Study findings and interpretation:
⋅ ASTRAL-5 was a large, single arm study of HIV/HCV co-infected individuals treated with SOF (400 mg) combined with VEL (100 mg) as a once daily single tablet regimen for 12 weeks (17). This regimen has previously been shown to be safe, well tolerated and to demonstrate high cure rates in HCV monoinfected individual with genotype 1 through 6. The study included 106 patients who were HCV genotypes 1 through 4, treatment naïve or experienced and included 30% with compensated cirrhosis on stable ART for at least 8 weeks with CD4 cells of at least 100 cells/uL with plasma HIV RNA <50 copies/mL on NNRTIs, integrase strand transfer inhibitors or protease inhibitor-based regimens combined with either TDF/FTC or ABC/3TC. The primary endpoint was sustained viral response at 12 weeks (SVR12). The study population included 73% with HCV genotype 1a or 1b with 10% being genotype 2, 11% genotype 3 and 5% genotype 4. There were no patients enrolled with genotypes 5 or 6. Fifty three percent were on TDF-based regimen with boosted 3rd drug with 33% on TDF-based regimen with non-boosted third drug and the remainder on ABC/3TC-based therapy. SVR12 rates were 95% overall (101 of 106) with little difference across the genotypes studied. There were 2 relapsers and 1 lost to f/u in the genotype 1a group, 1 lost to follow-up in the genotype 1b group, and 1 that withdrew consent in the genotype 3 group. Response rates varied little between those with or without cirrhosis, with 19 of 19 cirrhotic patients achieving SRV12, or in those treatment naïve or experienced with slightly higher response rate in the experienced than naïve group, 97 vs. 93%, respectively. Finally, those with NS5A resistance-associated variants at baseline, 12/103 (12%) all achieved SVR12. The regimen was well tolerated with only 2 discontinuing due to adverse events with most common laboratory abnormality being elevated bilirubin in those on boosted atazanavir. The most common adverse events were fatigue in 25% and headache in 13%, most being categorized as mild, i.e. grade 1 and 2. The overall conclusion is that this regimen is safe, well tolerated and highly effective in HIV/HCV co-infected patients with HCV genotype 1, 2, 3 and 4 virus regardless of cirrhosis status, presence of NS5A resistance variants and type of ART used, including TDF-based regimens with boosted third agents.
⋅ Another study assessed DDIs between SOF/VEL and various antiretroviral agents. The study used data from two phase 1, open-label multiple-dose studies of healthy volunteers with regimens including TDF/FTC, TAF/FTC in various combinations with third drugs including EFV, RPV, DTG, RAL, elvitegravir/cobicistat, ATV/r, darunavir/r and lopinavir/r (18). There were no meaningful interactions with SOF or its metabolite with any antiretrovirals tested. VEL exposure decreased by 50% when given with EFV, thus these drugs should not be given together. TDF-containing regimens given with SOF/VEL was associated with increased TFV exposure by 20-80% without meaningful impact on TFV exposure when TAF/FTC was used with SOF/VEL. The conclusion from this study is that SOF/VEL in coinfected patients can be given with all tested agents except EFV, with further data on safety likely to emerge from ASTRAL-5 study.
CONCLUSIONS
It was great to see this meeting return to South Africa for the third time and to reflect on the changes that have occurred over the past 15+ years. While the roll out of ART in resource limited settings has been very impactful, it is also clear that there has been enormous advances in prevention and treatment that can have a profound impact on HIV/AIDS across the globe. My only regret is that there were so many important presentations that I could not cover. Consequently, I strongly encourage you to visit the IAC 2016 web site for more information (http://www.aids2016.org/).
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, Janssen, Merck, Teva and ViiV.
REFERENCES
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2. Bekker LG, Laher F, Moodie Z, et al. Meeting the "Go" criteria: Immunogenicity from HVTN 100, a phase ½ randomized, double blind, placebo-controlled trial of clade C ALVAC- ® (vCP2438) and bivalent subtype C gp120/MF59® in HIV-uninfected South African adults. 21st International AIDS Conference 2016, Durban, South Africa, Abstract TUAX0102LB.
3. Molina JM, Charreau I, Spire B, et al. Efficacy of "On Demand" PrEP in the ANRS IPERGAY open-label extension Study. 21st International AIDS Conference 2016, Durban, South Africa, Abstract WEAC0101.
4. Mera R, McCallister S, Palmer B, et al. Truvada (TVD) for HIV pre-exposure prophylaxis (PrEP) utilization in the United States (2013-2015). 21st International AIDS Conference 2016, Durban, South Africa, Abstract TUAX0105LB.
5. Brown ER, Palanee-Philips T, Marzinke M, et al. Residual dapivirine ring levels indicate higher adherence to vaginal ring is associated with HIV-1 protection. 21st International AIDS Conference 2016, Durban, South Africa, Abstract TUAC0105LB.
6. Rodger AJ, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA 2016; 316:171-181.
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8. Rodger A, Cambiano V, Bruun T, et al. Sexual activity without condoms and risk of HIV transmission when the HIV positive partner is using suppressive ART: The PARTNER study. 21st International AIDS Conference 2016, Durban, South Africa, Abstract TUAC0206.
9. Baeten JM, Heffron R, Kidoguchi L, et al. Integrated delivery of PrEP and ART results in sustained near elimination of HIV transmission in African HIV serodiscordant couples; Final results from the Partners Demonstration Project. 21st International AIDS Conference 2016, Durban, South Africa, Abstract WEAC0105.
10. Orrell C, Hagins D, Belonosova E, et al. Superior efficacy of dolutegravir/abacavir/lamivudine FDC compared with ritonavir-boosted atazanavir plus tenofovir disoproxil fumarate/emtricitabine FDC in treatment-naïve women with HIV-1 infection: ARIA Study. 21st International AIDS Conference 2016, Durban, South Africa, Abstract THAB0205LB.
11. Cahn P, Kaplan R, Sax P, et al Raltegravir (RAL) 1200 mg once daily (QD) is non-inferior to RAL 400 mg twice daily (BID), in combination with tenofovir/emtricitabine, in treatment-naïve HIV-1 infected subjects: Week 48 results. 21st International AIDS Conference 2016, Durban, South Africa, Abstract FRAB01013LB.
12. Cahn P, Rolon MJ, Figueroa MI, et al. Dolutegravir-lamivudine as initial therapy in HIV-infected, ARV naïve patients: 48 week results of the PADDLE trial. 21st International AIDS Conference 2016, Durban, South Africa, Abstract FRAB0104LB.
13. Lake J, Tottier B, Garcia-Diaz J, et al. STRIIVING: Switching to dolutegravir/abacavir/lamivudine fixed dose combination (DTG/ABC/3TC FDC) from a PI, INI or NNRTI based regimen maintains HIV suppression at 48 weeks. 21st International AIDS Conference 2016, Durban, South Africa, Abstract THAB0203.
14. Margollis D, Podzamczer D, Stellbrink H-J, et al. Cabotegravir + rilpivirine as long-acting maintenance therapy: LATTE-2 week 48 results. 21st International AIDS Conference 2016, Durban, South Africa, Abstract THAB0206LB.
15. Deeks SG, Lewin SR, Ross AL et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nature med 2016; 8:1-12.
16. Kroon E, Ananworanich J, Eubanks K, et al. Effect of vorinostat, hydroxychloroquine and maraviroc combination therapy on viremia following treatment interruption in individuals treated during acute infection. 21st International AIDS Conference 2016, Durban, South Africa, Abstract TUAX0101LB.
17. Brau N, Wyles D, Kottilil S, et al. Sofosbuvir/velpatasvir for 12 weeks in patients coinfected with HCV and HIV-1: The ASTRAL-5 study. 21st International AIDS Conference 2016, Durban, South Africa, Abstract WEAB0301.
18. Mogalian E, Luetkemeyer A, Naik S, et al. Drug-drug interactions studies between HCV antivirals sofosbuvir and velpatasvir and HIV antiretrovirals. 21st International AIDS Conference 2016, Durban, South Africa, Abstract WEAB0302.
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