ViralEd - CROI 2018 eSymposium

Switch to Bictegravir/F/TAF from DTG and ABC/3TC
(Molina JM, et al; Abstract 22):

Molina and colleagues presented the 48-week safety and efficacy results of a 1:1 switch to bictegravir/FTC/TAF from dolutegravir/ABC/3TC in 563 HIV-suppressed adults. Non-inferiority was established: After 48 weeks, 93.6% on B/F/TAF and 95.0% on DTG/ABC/3TC were <50 c/ml. There was no resistance in either arm, and few participants (6 [2%], 2 [1%], respectively) had AEs leading to drug discontinuation. Bone and renal markers were similar between arms, as were lipids, with the exception of a small decrease in triglycerides seen in the B/F/TAF group.

DRV/R/3TC FDC for HIV-1 Treatment-Naïve Patients: Week 48 Results of the ANDES Study
(Figueroa M, et al: Abstract 489):

Figueroa and colleagues presented the 48-week results of the open-labelled ANDES study in Argentina of double vs. triple drug regimens in 145-ART naïve patients comparing DRV/r + TDF/3TC (TT) to DRV/r + 3TC (DT). One quarter of subjects had a baseline VL > 100,000. At week 48, 93% of patients on DT and 94% on TT achieved VL <50 copies/mL. Median CD4+ changes were similar in both arms, and side effects were as expected with DRV/r and comparable between the two groups. Significantly more total cholesterol elevations were seen in the DT arm in the absence of TDF, 19% vs. 4%. This study adds credibility to the case for two drug regimens with boosted PIs in selected patients.

Safety and Efficacy of Dolutegravir-based ART in TB/HIV Co-infected Adults at Week 24
(Dooley K, et al; Abstract 33):

Dooley and colleagues presented the 24-week data from a randomized, open-label study of DTG vs EFV in ART naïve patients with ≥ 50 CD4 cells and active TB who recently initiated treatment. Participants on rifampin-based TB treatment for up to 8 weeks were randomized (3:2) to receive DTG (50 mg twice daily during and for 2 weeks post-TB therapy, followed by 50 mg once daily [QD]) or EFV (600 mg QD), with 2 investigator-selected NRTIs. Mean baseline VL and CD4 were 5.1-5.2 logs and 202-208 cells. 81% of subjects on DTG and 89% in the EFV arm had VL <50 c/mL at Week 24. CD4+ cell increases were 146 cells/μL for DTG and 93 cells/μL for EFV. Only two patients in the EFV arm stopped drug due to side effects. TB- IRIS incidence was low (6-9%) and not different between arms, and did not lead to discontinuations. This study adds a useful new option to the management of HIV-TB co-infected patients.

Age, Gender, and Race Analyses of D/C/F/TAF in HIV-1 Treatment-Naïve Patients
(Rashbaum B, et al; Abstract 492):

Rashbaum and colleagues presented the 48-week sub-group analyses of the AMBER non-inferiority trial comparing the fixed dose DRV/C/F/TAF to DRV/C + FTC/TDF in 725 ART naïve patients, of whom 68 (9.4%) were age >50 y, 85 (11.7%) women, and 80 (11.5%) black/AA. Overall, virologic response rates were 91.4% for D/C/F/TAF and 88.4% for DRV/c + FTC/TDF. Responses were similar across age, gender, and race subgroups. AEs were similar in both groups. In bone (bone loss/atrophy AEs, bone mineral density) and renal (eGFR) safety parameters were observed for D/C/F/TAF across subgroups.

Similar Efficacy & Safety by Subgroup in DRIVE-AHEAD: DOR/3TC/TDF versus EFV/FTC/TDF
(Orkin C, et al; Abstract 491):

Orkin and colleagues presented the sub-group analyses of the DRIVE-AHEAD study of doravirine/3TC/TDF compared to EFV/FTC/TDF in 728 ART-naïve patients. Overall, 84% and 81% achieved a VL <50 c/ml. There were no significant differences in these outcomes by gender, race/ethnicity, viral sub-type, CD4 cell count, and baseline viral load. Adverse events were few and similar between the sub-groups.

HIV Diagnoses Among People Who Inject Drugs – United States, 2010-2015
(Lyss S, et al; Abstract 970)

Lyss and colleagues from the U.S. CDC presented updated the changes in the epidemiology of HIV in people who inject drugs (PWIDs) using the National HIV Surveillance System. HIV diagnoses in PWID decreased 35% from 2010-2014. In contrast, from 2014-2015, HIV in PWID in the US increased 5%. Increases occurred in whites (+32%), people aged 13-34 years (+22%), and in the Midwest (+ 85%), all consistent with the local epidemic in Scott County, IN in 2015. The authors noted that vigilance is needed to maintain the longstanding gains in reducing HIV in PWIDs in the US.

Characteristics of HIV Incident Infections Among Persons Who Inject Drugs in the US
(Chapin-Bardales J, et al; Abstract 971):

In a companion CDC presentation on the shifting epidemiology of IDUs in the US, Chapin-Bardales and colleagues characterized recent HIV infections in IDUs in a sample of PWIDs from 19 US cities. Recently HIV infected were significantly more likely in the past year to inject stimulants such as crystal meth, have a greater number of sex partners, and have had male-male sex. PWID who have sex with men were highest among recent infections. Recently infected PWID were more likely to be young, white, have a high school diploma, not have health insurance, share syringes, have a greater number of sex partners, and have condom-less sex in the past year. Taken together, these studies point to the remarkable ability of HIV to infect new groups of vulnerable Americans, and call attention to the growing impact of the opioid and methamphetamine epidemics in the US and the need for harm reduction and targeted prevention and treatment programs.

Pooled Week 48 Efficacy and Baseline Resistance: B/F/TAF in Treatment-Naïve Patients
(White K, et al; Abstract 532):

White and colleagues presented the pooled efficacy and baseline resistance analysis of 1,274 patients in the 1489 and 1490 studies of bictegravir/FTC/TAF (B/F/TAF) compared to DTG/ABC/3TC and DTG + F/TAF, respectively. 91% were <50 c/ml at wk 48 in the B/F/TAF group and 93% in the comparators. Primary resistance mutations were found in 18% of patients overall, as follows: NRTI – 2.5%, NNRTI - 12%, PI-R - 2.5%, and INSTI-R - 1.0%. One subject in the B/F/TAF group had Q148H+G140S at baseline and was suppressed with HIV-1 RNA <50 c/mL at W48. Viral suppression was similar with or without pre-existing resistance mutations. 1.3-1.5% had resistance testing during the studies, and none had emergent resistance to study drugs. In sum, all three regimens rapidly achieved viral suppression with no impact of pre-existing mutations, and no resistance mutations emerged during the study.

One Month of Rifapentine/Isoniazid to Prevent TB in People with HIV: Brief-TB/A5279
(Swindells S, et al; Abstract 37LB)

Swindells and colleagues presented a study that may have the greatest global impact of any presentation at CROI this year, a comparison of 1-month treatment with once daily isoniazid (INH) and rifapentine (SHORT) vs. standard 9-month treatment with INH (STND) for latent TB by TST or IGRA in HIV/TB co-infected patients. ART was either EFV- or NVP-based, and the primary endpoints were incident TB, death from TB, and all-cause mortality. Of 3,000 pts, 634 (21%) had a positive TST, and another 70 had a positive IGRA. Median CD4 was 470, and 50% were on ART. TB incidence rates were 0.65/100 PY for SHORT and 0.67 for STND, meeting the criteria for non-inferiority for the SHORT course. Higher overall rates were seen with no ART, with a lower CD4 cell count, and with a positive TST or IGRA, but not different between arms. SAEs were 5.6% for SHORT and 7.1% for STND. TB treatment completion was higher in SHORT (97%) than STND (89%) (P<0.01). In sum, the short course was non-inferior, had fewer adverse events, and was more likely to be completed than standard treatment. This study is likely to change the paradigm for the optimal management of TB globally, and to introduce a new opportunity to offer a more user-friendly treatment of latent TB.

Platelet Function Upon Switching to TAF vs Continuing ABC: A Randomized Sub-study
(Mallon P, et al; Abstract 80):

Mallon and colleagues conducted a sub-study of platelet aggregation at 4 and 12 weeks in 61 patients switched from ABC/3TC to FTC/TAF. Baseline aggregation was comparable with 5 agonists. Through week 12, significantly lower platelet reactivity to 2 agonists – thrombin receptor activating peptide and adenosine diphosphate - was seen at 4 weeks, and to collagen through 12 weeks. The finding of lower platelet reactivity following a switch from ABC/3TC to FTC/TAF may offer some insight into the pathogenesis of accelerated cardiovascular disease that has been associated with short-term use of abacavir.

Combined Effects of Bisphosphonates & TDF→TAF Switch in HIV+ Adults with Low BMD
(Brown T, et al; Abstract 724):

Brown and colleagues studied the relative and additive benefits of a switch to TAF or the use of bisphosphonates for osteoporosis in a sub-set of patients with viral control who switched to ELV/C/F/TAF and who had T scores < 2.0 at baseline. Of 1,117 subjects, 214 (19%) had low BMD, and of those, 43% had osteoporosis. Bisphosphonates were used by 14% of pts with low BMD during the study and were associated with 5.1% increase in spine BMD and 4% increase in hip BMD, compared to 2.6% and 2.3% for non-users, respectively; the spine changes were significant (P=0.002), and the hip changes were not. In sum, the switch to TAF improved BMD in this sub-study, and the addition of a bisphosphonate added significantly in the spine, but not in the hip.

By Race/Ethnicity, Blacks have Highest Number Needing PrEP in the United States, 2015
(Smith D, et al; Abstract 86):

Smith and colleagues from the U.S. CDC presented compelling data on the estimated national need for PrEP among at-risk individuals with reliance on the estimated prevalence of high-risk behavior and a PrEP indication among MSM in the U.S. of 24.7%. The total estimated need for PrEP in the U.S. in 2015 was 1.1 million persons. By race, 500,340 were black (44%), 303,230 were white, 282,260 were Hispanic/Latino (Latino), and 58,720 were of other race/ethnicities. 71% were MSM, and of these, 38% were black, 29% were white, and 27% were Latino. The need in heterosexuals at risk was estimated to be 258,080, of whom 68% were female, 64% were black, 18% were Latino, and 14% were white. And among PWID at risk, 39% were white, 37% were black, and 21% were Latino, reflecting the evolving impact of the opioid epidemic. By region, the highest needs were in the South. These data dramatically underscore the need to address the inequities in PrEP access at present in the U.S. and to focus on engagement in care and HIV testing, prevention, and PrEP for at-risk individuals.