HPTN 083 interim results: Pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB-LA) is safe and highly effective for cisgender men and transgender women who have sex with men (MSM, TGW) (Landovitz R, et al; Abstract OAXLB0101) and HPTN 083 interim results: Efficacy of pre-exposure prophylaxis (PrEP) containing long-acting injectable cabotegravir (CAB-LA) is maintained across regions and key populations (Grinsztejn B, et al; Abstract OACLB0101):

Landovitz and colleagues present the results of the HPTN 083 comparison of long-acting cabotegravir in 2 monthly injections to oral TDF/FTC in 4,566 at-risk MSM and TGW, with the entry requirement of >50% under age 30, >10% TGW, and >50% black. The trial was stopped at a DSMB review in May 2020, and study retention was 91%, 87%, and 76% at 6, 12, and 24 months. 13 HIV infections were seen in the CAB arm for a rate of 0.41%, and 39 in the TDF/FTC arm for a rate of 1.2%. 87% of TDF/FTC users had detectable levels, and 75% had pK reflecting daily dosing. Site injection pain and redness were seen in 57% of CAB subjects and were mostly mild-moderate, leading to drug d/c in 47 (2.2%) of subjects in the CAB arm. While both arms were highly effective, cabotegravir met criteria for superiority. In a companion presentation, Grinsztjen and colleagues showed that these results were observed regardless of gender, age, region, or race/ethnicity. This groundbreaking study adds an important tool to the HIV prevention toolbox for MSM and TGW, and additional studies are needed to explore its use in women, in other
at-risk populations, and in a variety of clinical settings.

PrEP prescription abandonment at the pharmacy, United States, 2018
(Huang Y, et al; Abstract LBPEC22):

Huang and colleagues at the CDC reviewed 195,061 PrEP prescriptions in the U.S. in 2018 and found that 15,472 (7.9%) of patients abandoned their prescriptions. New PrEP patients, women, patients age <25 years or >65 years, cash payers, and patients with a high copayment had higher rates of abandonment. 52% of PrEP patients who paid cash abandoned their prescriptions, and they were 3.1 times more likely, and those with a high co-pay were 2 times more likely, to abandon their prescriptions. Financial barriers remain a critical barrier to effective PrEP implementation.

COVID-19 in the largest US HIV cohort (Park L, et al; Abstract LBPEC23):

Park and colleagues at the Veterans Aging Cohort Study (VACS) presented their experience with COVID-19 in the largest HIV cohort in the U.S., with 30,981 PLWHIV and 76,745 age-matched controls. COVID-19 was diagnosed in 189 PLWHIV
(12.7% of tested) and 380 uninfected (13.9%), with no major differences in baseline characteristics. In both groups, higher incidence rates were seen in persons of color, and the risk of severe COVID-19 outcomes was similar in both groups. These data are reassuring in support of the growing evidence of no higher incidence or disease severity of COVID-19 among PLWHIV.

Comparative outcomes in hospital admissions with COVID-19 in people living with HIV
and people living without HIV: A retrospective study (Lee M, et al; Abstract LBPEB09):

Lee and colleagues compared the course of COVID-19 in 17 PLWHIV and 50 non-HIV matched controls in a single hospital in the UK. There were no deaths among the HIV patients, of whom 15 (88%) had an undetectable VL, compared to 5 (10%) deaths among HIV negative patients, and they found no evidence of more severe illness among patients with HIV. In contrast, PLWHIV were significantly more likely to achieve a clinical improvement from baseline or discharge from hospital than non-HIV patients. These data further reinforce the observation that PLWHIV who are virologically controlled do not have a more severe illness with COVID-19 than non-HIV infected individuals.

Racial disparities and high rates of exposure to congregate settings among a cohort of people living with HIV and COVID-19 (Meyerowitz E, et al; Abstract LBPEB13):

Meyerowitz and colleagues compared the course of COVID-19 in 36 PLWHIV in Boston, of whom nearly 60% were hospitalized, 8 had severe disease requiring oxygen supplementation, 7 required ICU care, and two patients died. 85% had co-morbidities, including obesity (33%), HTN (31%), DM (22%), and CKD (22%), and nearly half lived or worked in a congregate living setting. 77% of the group were persons of color, compared to 40% in the HIV clinic overall, underscoring the vulnerability of Latinx and African American PLWHIV in the U.S. to COVID-19.

GS-6207 sustained delivery formulation supports 6-month dosing interval
(Begley R, et al; Abstract PEB0265):

Begley and colleagues presented a glimpse of the future potential for long-acting drugs with a pK study in healthy volunteers
of the subcutaneous administration of the novel capsid inhibitor GS-6207 at a dose of 300 mg or 900 mg. The safety was satisfactory, with mild grade induration reported (87% of subjects), erythema (70% of subjects), and pain (63% of subjects). Maximal drug concentrations were seen at 11-14 weeks. At the 900 mg dose, sustained therapeutic drug levels were observed for 6 months post-dose. Plans for clinical trials in HIV infected persons with a 6-month dosing interval are underway.

Virological efficacy and tolerability of dual therapy maintenance with dolutegravir plus lamivudine in heavily treatment experienced HIV-infected patients: Four years data from DOLULAM study (Reynes J, et al; Abstract PEB0241):

Reynes and colleagues presented the 4-year follow-up findings of the DOLULAM study of the 2 drug combination
dolutegravir + lamivudine in 27 treatment-experienced patients, of whom 37% had a known M184V mutation, offering one of the longest periods of follow up to date in a group on ART for a median of 17 years, and on their previous regimen for a median of 51 months (13-108 months), most often a boosted PI (81%). There were no virologic failures, and 4 discontinuations, 3 for personal reasons and one for low level viremia. No weight gain was observed among the study subjects after 4 years. These observations provide some reassurance for the durability of DTG/3TC in treatment-experienced patients with an M184V mutation.

PrEP continuum of care and new HIV infections: Long-term follow-up in a large clinical cohort (Volk J, et al; Abstract OAC0807):

Volk and colleagues presented the extensive PrEP care continuum experience among 12,963 patients linked to PrEP care at Kaiser Permanente, of whom 95% were male and 50% were white. Of this group, 80% received a prescription and 66% started treatment, and PrEP persistence at 1, 3, and 5 years was 73%, 60% and 56%. 37% of those who dropped PrEP restarted at a later time. African Americans were 19% less likely to start PrEP, and 18% more likely to discontinue PrEP. HIV incidence rates were highest among those who stopped PrEP (1.5%), and lowest among those who persisted on PrEP (0.14%). These real-world data are essential to assess the positive impact of PrEP and to address the barriers by race and ethnicity to PrEP access and persistence.

Estimated time from HIV infection to diagnosis, 50 U.S. states and the District of Columbia, 2014-2017 (Crepaz N, et al; Abstract OAC0206):

In a discouraging analysis from CDC, Crepaz and colleagues updated the mean time from HIV diagnosis to treatment in 195,052 PWHIV in the United States from 2014-2018 using the National HIV Surveillance System. Although the mean time improved annually with a 2.3% annual decline, it was still 39 months in 2018. The largest improvements were seen in the West and the South, but the median time was over 3 years in three quarters of reporting jurisdictions. There is still much work to be done to shorten the time from HIV infection to treatment with ART in the United States.

Compassionate use of long acting (LA) cabotegravir (CAB) and rilpivirine (RPV) for patients
in need of parenteral antiretroviral therapy (D'Amico R, et al; Abstract PEB0263):

D'Amico and colleagues presented the results of the compassionate access usage of co-formulated CAB/RPV in 35 patients who were unable to manage oral medications. The main indications were chronic non-adherence to oral medications (9) or GI (9 - malabsorption [6] or dysphagia [3]). Eleven patients were perinatally infected. Of 7 patients with suppressed VL at entry, all remained suppressed. Of 28 with viremia at entry, 16 (57%) suppressed after a median 2 mos of treatment. Two patients had VL failure with emergent NNRTI mutations and no INSTI mutations, and 3 patients had serious adverse effects. These data are encouraging for patients and clinicians facing the difficult problem of refractory non-adherence to oral medications or chronic malabsorption, and underscore the need for caution in the use of this two-drug regimen in the presence of VL failure and prior ART resistance.

Update on neural tube defects with antiretroviral exposure in the Tsepamo study, Botswana (Zash R, et al; Abstract OAXLB0102):

Zash and colleagues presented the updated results of the TSEPAMO study of the use of DTG or EFV in HIV+ pregnant women. In the updated analysis, with one additional case of neural tube defects (NTD) in women on DTG at conception for a total of 7 of 3,591 exposures, the risk of NTD in women on DTG at the time of conception fell from 0.30% to 0.19%. The investigators noted that this outcome will result in one additional case of NTD per 1,000 births. The investigators explained that this finding is now not statistically different from NTD incidence with other ART regimens, and with that of the general population. These data provide reassurance to the continued use of DTG in women of child-bearing age with appropriate engagement and information sharing between clinician and patient.

Effects of INSTI and other ARV combinations on folate distribution via folate transporters: Implications for neural tube defects (Okochi H, et al; Abstract PEA0084):

Okochi and colleagues added to our understanding of dolutegravir and neural tube defects with a demonstration of interference with the folic acid transporters SLC46A1 and SLC19A1. While DTG alone did not inhibit folate uptake, combinations of TDF/FTC, DTG/ABC/3TC, and DTG/TDF/3TC inhibited >50% of SLC19A1 activity. These findings offer a possible insight into the mechanism of DTG-induced neural tube defects and reinforce the importance of pre-conception dietary folic acid fortification for HIV+ women on INSTI-containing ART regimens.

Dolutegravir- versus low-dose Efavirenz-based regimen for the initial treatment of HIV-1 infection in Cameroon: Week 96 results of the ANRS 12313 - NAMSAL trial
(Kouanfack C, et al; Abstract OAB0402):

Kouanfack and colleagues presented the 96-week results of the NAMSAL study comparing DTG + TDF/FTC (n=310) to low-dose EFV + TDF/FTC (n=303) in which the median age was 36 yrs, and 68% were women. Viral loads were >100k in 66%,
and 33% had a CD4 <200 cells/mL. Overall, the DTG arm met the non-inferiority criteria, with 73.9% and 72.3% achieving VL <50 c/ml, respectively. Weight gain was higher in the DTG arm vs. the EFV arm (6.7 kg vs. 4.2 kg), and a higher percentage of patients in the DTG arm became obese (22% vs. 16%).

Analysis of protocol defined virologic failure through week 48 from a phase 2 trial (P011)
of islatravir and doravirine in treatment-naïve adults with HIV-1 infection
(Orkin C, et al; Abstract OAB0302):

Orkin and colleagues presented an analysis of virologic failures in the phase II trial of doravirine + islatravir (DOR/ISL) in treatment-naïve patients who first received DOR + 3TC + ISL and were switched to the two-drug regimen after week 20 when VL control was established. All participants with PDVF had confirmatory HIV-1 RNA levels <80 copies/mL There were 6 patients who met study defined criteria for VL failure, all of whom had VL between 50-100 c/mL, and no participants met the criteria for resistance testing (HIV-1 RNA >400 copies/mL). The pK for ISL for participants who experienced PDVF was similar to other participants at the same dose level, and the once daily co-formulation of DOR/ISL is in multiple clinical trials.

Doravirine resistance profile in clinical isolates and impact of baseline NNRTI resistance-associated mutations observed in treatment-naïve participants from phase 3 clinical trials (Asanti-Appiah E, et al; Abstract PDB0406):

Asanti-Appiah and colleagues presented the baseline resistance profiles of 4,070 treatment-naïve and experienced patients
in doravirine clinical trials. Using a 5x DOR cut off, 92.5% of samples were susceptible to DOR, compared to NVP (77.5%),
EFV (81.5%), RPV (89.5%), and ETR (91.5%). Five or more NNRTI resistance mutations were required to confer reduced susceptibility to DOR; in addition, rare NNRTI mutations at the Y188L and Y318F loci were associated with 11-41 fold reduction in susceptibility. These data offer greater insights into the high barrier to resistance with doravirine compared to other NNTIs.

Sub-optimal outcomes with switching to zidovudine vs. recycling tenofovir in second-line treatment in Haiti (Pierre S, et al; Abstract OAB0405):

Pierre and colleagues presented an important study in Haiti in 1,017 patients requiring second-line regimens comparing
a switch to ZDV to continuation of TDF in combination with lamivudine and a boosted PI. Retention was good, with 83% retained in care at 12 months in both arms during the study. 72/200 (36%) of patients in the ZDV arm had a VL <200 at 12 mos, compared to 253/480 (52.7%) in the TDF arm. Adherence was better in the TDF arm (72%) than the ZDV arm (57%). The investigators suggested that adherence to the twice-daily ZDV dosing and tolerability were the main reasons for the adverse outcomes. These are important outcomes to consider in the application of the WHO guidelines for second-line ART in resource limited settings.