CABOTEGRAVIR + RILPIVIRINE EVERY 2 MONTHS IS NONINFERIOR TO MONTHLY:
ATLAS-2M STUDY (Overton E, et al; Abstract #34):

Overton and colleagues presented the 48-week data on 1,045 patients in the ATLAS-2M comparison of long-acting cabotegravir/rilpivirine (CAB/RPV) at intervals of 1 or 2 months with a non-inferiority design. The doses were 600 mg CAB/900 mg RPV (2 months) and 400 mg CAB/600 mg RPV (1 month). 63% of subjects were naïve to CAB/RPV and 37% transitioned from earlier ATLAS studies. All patients were first exposed to oral CAB/RPV for 4 weeks prior to IM Rx. VL failures were 1.7% and 1%, and VL suppression was 94.3% and 93.5%, respectively, so the 2-month arm met non-inferiority criteria with both endpoints. 2% of patients discontinued the drug due to toxicity. Confirmed VL failures were 8 and 2 respectively, and 6/8 and 1/2 of these had archived resistance mutations to RPV alone or with a CAB RAM prior to initiation. During treatment, new INSTI resistance mutations developed in 5/8 (2 month) and 2/2 (1 month) patients with confirmed VL failure. 98% of injection site reactions were mild to moderate severity and lasted a median of 3 days, and 98% of patients preferred Q8W dosing over oral dosing. These findings support a more user and clinic-friendly 2-month interval for the use of long-acting cabotegravir/rilpivirine.

RANDOMIZED SWITCH TO B/F/TAF IN AFRICAN AMERICAN ADULTS WITH HIV
(Hagins D, et al; Abstract #36):

Hagins and colleagues presented the 24-week results of a switch trial in U.S. African American PWHIV with viral suppression with a 2:1 randomization to BIC/FTC/TAF vs. their current regimen (SBR). The baseline ART was INSTI in 61%, NNRTI in 31%, and PI/r in 9%. Patients with K65R/E/N, 3 or more TAMS or T69 insertions, or primary INSTI resistance were excluded. Of 558 screened, 495 patients were randomized to BIC/FTC/TAF (330) or SBR (165). 11% of patients had M184V at baseline, and 20% had NNRTI resistance. At 24 weeks, 0.6% and 1.8%, respectively, had VL >50 c/mL, and 96% and 95% of patients had VL < 50 c/mL, and the non-inferiority criteria were met. 6 patients on BIC/FTC/TAF discontinued ART due to side effects vs. 0 patients on SBR. No differences in viral outcomes were seen with pre-existing NRTI mutations. These preliminary data suggest that a switch to BIC/FTC/TAF is an effective strategy alternative among AA PLWHIV in the U.S.; it will be important to observe the results over a longer follow-up period to gauge the duration of these findings.

PREDICTED 10-YEAR RISKS OF DIABETES AND CARDIOVASCULAR DISEASE
IN THE ADVANCE TRIAL (Hill A, et al; Abstract #81):

Hill and colleagues reported the risk of DM, CVD and metabolic syndrome (met syn) in the ADVANCE trial in 1,053 treatment-naïve HIV+ patients in South Africa, comparing TAF/FTC + DTG, TDF/FTC + DTG, and TDF/FTC/EFV. In an earlier presentation of this study, a greater incidence of weight gain (5.8 kg) was seen in the TAF/FTC + DTG arm after 96 weeks compared to TDF/FTC+DTG (2.4 kg) or TDF/FTC/EFV (0.5 kg). HTN, DM, and met syn were present in 9%, 1%, and 5% of patients, respectively. Incident met syn was greatest with TAF/FTC + DTG (8%) than with TDF/FTC + DTG (6%) and TDF/FTC/EFV (3%). Risk of DM was greater in patients on TAF/FTC + DTG than TDF/FTC + DTG (P=0.005), and CVD was also significantly greater in the TAF/FTC + DTG arm compared to TDF/FTC + DTG. Further studies of the relative contribution of each ART component will be important to better understand the pathogenesis of metabolic syndrome, DM, and cardiovascular risk in HIV+ patients.

CYP2B6 GENOTYPE AND WEIGHT-GAIN DIFFERENCES BETWEEN DOLUTEGRAVIR
AND EFAVIRENZ (Griesel R, et al; Abstract #82):

Griesel and colleagues conducted a sub-study in the ADVANCE trial of the relationship between the CYP2B6 genotype and incident weight gain in the TDF/FTC/EFV study arm. Of 171 pts, CYP2B6 genotypes were found to be slow (46), intermediate (74), or extensive (51). In women, weight gain was greatest among those with the extensive genotype and was similar to the weight gain observed with TDF/FTC+DTG; this effect was less striking in men. In women, extensive CYP2B6 genotype was also associated with a greater degree of lipoatrophy. The authors noted the multifactorial contribution to weight gain among PWHIV and the importance of variations in CYP2B6 genotypes on EFV metabolism and weight gain.

CHANGES IN BODY MASS INDEX AND THE RISK OF CARDIOVASCULAR DISEASE:
THE D:A:D STUDY (Petoumenos K, et al; Abstract #83):

Petoumenos and colleagues reported the results of an analysis of the D:A:D study in which the association between BMI and the risk of CDV and DM was explored in 43,011 HIV+ patients in whom there were 1,583 DM events and 2,104 CVD events. Increases in BMI were not associated with increased risk of CVD, but were associated with a 1.5-2x increased risk of DM. The enormous power of these observations, due to the large numbers of patients and the prospective clinical outcomes, give additional weight to these findings.

LOSARTAN TO REDUCE INFLAMMATION AND FIBROSIS ENDPOINTS IN HIV DISEASE
"LIFE HIV Study" (Baker JV, et al; Abstract #84):

Baker and colleagues extended our search for a suitable therapy for chronic inflammation in a study of the angiotensin receptor blocker losartan, which is known to have anti-inflammatory properties. They randomized 108 patients to receive losartan (100 mg daily) or placebo for 12 months. Patients were 96% male, 44% non-white, 20% current smokers, and 49% on an INSTI. Losartan reduced systolic and diastolic blood pressure by 6 and 5 mmHg, respectively, but no effect was seen on markers of inflammation, immune activation, fibrotic activity, or T-cell immune recovery. Unfortunately, the search for a suitable therapeutic approach to the chronic inflammation and immune activation in HIV disease continues.

FTC/TAF + BIC POSTEXPOSURE PROPHYLAXIS PROTECTS MACAQUES AGAINST RECTAL SHIV INFECTION (Bekerman E, et al; Abstract #87), ON-DEMAND HIV POSTEXPOSURE PROPHYLAXIS BY TAF/EVG VAGINAL INSERTS IN MACAQUES (Dobard C, et al; Abstract #88), WEEKLY ORAL ISLATRAVIR PROVIDES EFFECTIVE PEP AGAINST IV CHALLENGE WITH SIVMAC251 (Grobler JA, et al; Abstract #89LB):

Three presentations offered hope for innovative strategies for post-exposure prophylaxis in pre-clinical macaque studies. Bekerman and colleagues (#87) reported that two doses of FTC/TAF + BIC (200 mg/25 mg + 100 mg) as post-exposure prophylaxis in macaques given at 6 hours and 30 hours post-exposure were protective in 5/6 macaques, and in 4/6 macaques when given at intervals of 12 and 36 hours post-exposure. Dobard and colleagues (#88) studied co-formulated TAF + EVG (20 mg/16 mg) as a vaginal or rectal insert, and found that 6/6 macaques were protected after 13 vaginal SHIV challenges and a 20-week follow-up period. And Grobler and colleagues (#89) studied the effect of a single dose of islatravir (3.9 mg/kg) with 4, 3, 2, and 1 dose in weeks 1, 2, 3, and 4, respectively. While all unprotected macaques became infected, 6/6 macaques were protected throughout the first 3 weeks of the study, and 2/6 became infected in week 4. The investigators noted that drug levels from a single oral dose of islatravir when extrapolated to human pharmacokinetics suggests that a single dose taken 24 hours post-exposure might provide comparable protection in humans as post-exposure prophylaxis, a speculation that awaits clinical trials in humans. Taken together, these studies offer new hope for progress in the simplification and further improvement of post-exposure prophylaxis, an intervention that has been neglected for too long in HIV prevention research.

SAFETY AND EFFICACY OF DTG VS EFV AND TDF VS TAF IN PREGNANCY:
IMPAACT 2010 TRIAL (Chinula L, et al; Abstract #130LB):

Chinula and colleagues (#130LB) presented the results of the IMPAACT 2010 trial in which 643 pregnant women in Africa were randomized to TAF/FTC + DTG, TDF/FTC + DTG, and EVF/TDF/FTC at 14-28 weeks gestational age. VL suppression at delivery was achieved in 97.5% of evaluable women on DTG regimens and 91% in the EFV arm (P=0.005). Significantly fewer adverse pregnancy outcomes were seen in the TAF/FTC + DTG arm (24%) than TDF/FTC + DTG (32.9%) or TDF/FTC/EFV (32.7%). Pre-term delivery, small for gestational age, and stillbirth were observed in (%) 5.8/16.3/3.7, 9.4/22.5/5.2, and 12.1/20.5/1.9, respectively. Two babies were diagnosed with HIV at 14 days, one in each DTG arm, and one with VL suppression and the other with 58,590 c/mL in the mother at delivery. Weight gain was highest among patients in the DTG + TAF/FTC arm, and was closest to the amount of weight gain expected in pregnancy among the arms. These findings further reinforce the superiority of DTG over EFV for virologic suppression in pregnant women, and suggest that TAF may be associated with a lower rate of adverse birth outcomes. If supported by additional studies, these findings may offer a new paradigm for the optimal management of HIV in pregnancy.

LONG-ACTING CABOTEGRAVIR + RILPIVIRINE FOR HIV TREATMENT:
FLAIR WEEK 96 RESULTS (Orkin C, et al; Abstract #482PS):

Orkin and colleagues presented the 96-week results of the FLAIR trial, a comparison of injectable long-acting cabotegravir/rilpivirine (CAB/RPV) to DTG/ABC/3TC in 566 ART-naïve patients with HIV for maintenance virologic suppression. At Week 96, virologic success was maintained in 86.6% and 89.4% of patients, respectively, and the non-inferiority criteria were met. No new virologic failures occurred between weeks 48 and 96 in the CAB/RPV arm, and no new resistance mutations occurred. Discontinuations due to AER were low, 4.2% and 1.4%, respectively, and most for CAB/RPV were due to grade 1-2 injection reactions. Weight gain was highest among patients in the DTG + TAF/FTC arm, and was closest to the amount of weight gain expected in pregnancy among the arms. Client satisfaction with the monthly long-acting injectable arm was significantly higher (P<0.001) than with the oral arm. These data lend further support to the potential for long-acting virologic maintenance suppression.

TESTOSTERONE THERAPY AND SUBCLINICAL ATHEROSCLEROSIS PROGRESSION AMONG MEN WITH HIV (Haberlen SA, et al; Abstract #642):

Haberlen and colleagues in the MACS reported a longitudinal analysis over 4.5 years of the CVD risk in older men aged 40-70 in the MACS CVD sub-study in the U.S. who use testosterone supplementation, as measured by coronary artery calcium (CAC), total plaque volume, and non-calcified plaque volume. In 300 men, mean age was 51, 48% were white, 91% were on ART and 81% had undetectable VL at entry. 70% never used TST, 8% were former users, 7% were new users, and 15% were continuous users. Risk of CVD by CAC progression over 4.5 years was 2x and 2.4x higher among continuous TST users and new TST users, respectively. Changes in plaque volume were not significant. One key question is whether the TST use was supplemental or replacement therapy for hypogonadism. These data add further evidence to the potential contribution of androgen treatment to CVD risk in HIV+ men.

POSTPARTUM WEIGHT CHANGES IN WOMEN INITIATING DTG VS EFV IN PREGNANCY: DOLPHIN-2 (Malaba T, et al; Abstract #771):

Malaba and colleagues presented data on post-partum (pp) weight changes in the DOLPHIN-2 study of DTG vs. EFV + 2 NRTIs in late pregnancy (>28 weeks). Mean weights in the 3rd trimester were higher in South Africa (80 kg) than in Uganda (67 kg). Breastfeeding at 12, 24, and 48 weeks pp was reported in 73%, 61%, and 3% of participants. From 4 weeks antepartum to 6 weeks pp, a mean 6.1 kg weight loss was found, with stable weights thereafter, and no significant differences in pp weight changes were seen in the DTG and EFV arms. More pp weight gain was seen among South African women (2.8 vs. -0.6 kg), and the investigators encouraged further study of regional and interpersonal differences in weight gain in the post-partum period.

DOLUTEGRAVIR USE IS ASSOCIATED WITH HIGHER POSTPARTUM WEIGHT COMPARED
TO EFAVIRENZ (Jao J, et al; Abstract #772):

Jao and colleagues reported results on weight gain during pregnancy and the post-partum (pp) period in 284 women in Botswana on DTG or EFV in the Tshilo Dikotia study of both HIV+ and HIV- pregnant women. Weekly weight gain in the 2nd and 3rd trimester were highest in HIV- women (0.3 kg/week) vs. w/DTG (0.2 kg/week) and EFV (0.1 kg/week). Compared to HIV- women, WHIV on DTG had similar weight after 18 months, and both were 5 kg heavier than WLHIV on EFV after 18 months pp. No differences were seen in income, gestational DM, or BMI that might partially explain differential weight gain, and the investigators noted that more study of the many factors that lead to post-partum weight gain in WHIV is still needed.

HIGH PROBABILITY OF SURVIVAL IN PATIENTS WHO MAINTAIN VIRAL LOADS <200 COPIES/ML (Lee JS, et al; Abstract #863):

Lee et al presented an analysis of the impact of low-level viremia on mortality risk of 19,465 patients with HIV from 2007-2016. Low-level viremia or blips were defined as 20-199 c/mL, and the analysis compared patients with VL suppression throughout their course with patients with one or more blips. Patient survival over 2 years was 97% for both groups, with no apparent impact of blips. These data add to the evidence that episodes of low-level viremia have no impact on survival, and they support the current guideline recommendation that the goal of therapy is viral suppression to <200 c/mL, rather than an undetectable VL at a lower threshold.

SAME-DAY ART IN THAILAND: THE IMPACT OF ART INITIATION PERIODS ON TREATMENT OUTCOMES (Seekaew P, et al; Abstract #1072):

Seekaew and colleagues presented the results of same day and early ART initiation in 4,642 HIV+ patients, of whom 3,888 started ART in 10 facilities in Thailand. Same day starts were done in 78.5% of patients, 12.5% started within 2-7 days, 4.2% started within 8-14 days; 1.3% started withing 14-21 days; and the rest started after 21 days. Retention rates at 3/6/12 months were 94%/92%/96%, 94%/95%/96%, 96%/97%/100%, 95%/91%/100% and 97%/91%/95% respectively. VL suppression rates were 94%/94%/84%/100%/88%. AER rates were comparable across the Rx categories, and transgender women had significantly more losses to follow up and adverse events. The investigators concluded that viral suppression rates with same day starts were comparable to standard care, and no differences were seen in losses to follow up or adverse events. These data support the viability and effectiveness of same day starts across a large population.

RAPID START LEADS TO SUSTAINED VIRAL SUPPRESSION IN YOUNG PEOPLE
IN THE SOUTH (Seybolt L, et al; Abstract #1073):

Seybolt and colleagues reported on the Rapid Start (RS) initiative for same day ART in a federally qualified health center (FQHC) in New Orleans. Linkage to care and initiation of ART in RS were defined as within 72 hours and included labs and expedited insurance enrollment. Between 12/1/16 and 5/15/18, 124 patients enrolled in RS, of whom 93 (75%) were age >25 and 31 (25%) were <25 years. All patients chose to start ART, and viral suppression at 28 days and at 12 months in younger patients was 96.8% and 83.9%, respectively, and in older patients 97.9% and 92.5%. Retention in care was 96.8% and 97.9% for younger and older patients, respectively. These findings suggest that rapid start is associated with high rates of viral suppression and retention among older and younger adults after one year.