Update on neural tube defects with antiretroviral exposure in the Tsepamo study, Botswana. Zash, R. Abstract # OAXLB01
The Tsepamo Study has been evaluating birth outcomes in Botswana since 2014. In May 2018 this group reported the prevalence of neural tube defects (NTD) to be 0.94% in mothers taking dolutegravir (DTG) at time of conception compared to 0.12% in those on non-DTG ART. However, in an updated analysis (April 2019) these numbers were 0.30% vs 0.10% for a prevalence difference of only 0.20%. The authors reported new data through April 2020 on 39,200 births. Among women on DTG at conception, 7/3591 NTDs were found (0.19%). In comparison, NTDs occurred in 21 of 19,361 infants (0.11%) of women taking non-DTG antiretrovirals from conception. The prevalence of NTDs in infants was not significantly different between DTG and non-DTG antiretrovirals, including efavirenz. The prevalence of NTDs was also not significantly different from that seen in HIV-negative women (0.07%). These data show a gradual decline in NTDs since the original Tsepamo data were reported. The prevalence of NTDs among infants born to women on DTG at conception has stabilized at about 2 per 1000 deliveries.
Commentary: I believe these data continue to support the safe use of DTG in women of child-bearing age as recommended by the current DHHS guidelines. DTG is noted to be an “Alternative” ARV drug for women who are trying to conceive and a “Preferred” ARV drug throughout pregnancy. View the full presentation by Dr. Zash HERE
PrEP continuum of care and new HIV infections: Long-term follow-up in a large clinical cohort. Jonathan Volk J. Abstract # OAC0807
This study from Kaiser Permanente (California) evaluated the PrEP continuum of care and new HIV infections over five years or more of follow-up. The authors used EHR data on members who were linked to care from 2012 to 2019. “PrEP prescription” was defined as a prescription written by a provider, “initiation” as a pharmacy fill by 6 months of linkage, and “persistence” as <120 days since last day of PrEP based on pharmacy fills. During this time period 12,963 patients linked to PrEP care, of whom 10,310 (80%) received a prescription and 8,571 (66%) initiated PrEP. This translates to 12,810 person-years of PrEP use or a mean use of 1.9 years/person. African Americans in this cohort were less likely to receive a prescription, less likely to initiate PrEP and more likely to discontinue it. PrEP persistence was 73%, 64%, 60%, 57%, and 56% at years 1 through 5 respectively. Overall, there were 136 new HIV infections. This included 42 at the time of PrEP linkage and 37 among those who were linked to care but never started PrEP. There were 13 infections among those who received a prescription but never initiated it. There were 38 infections among those who discontinued PrEP and 6 infections among those who were persistent on PrEP. The 6 with HIV who were “persistent” on PrEP all self-reported suboptimal adherence. There were NO new HIV infections in 12,810 person-years in those adherent to PrEP.
Commentary: This study continues to show how effective TDF/FTC is for HIV prevention if taken consistently. However, the overall numbers along the continuum remain sub-optimal on several levels. More work must be done to address racial disparities in the PrEP continuum and also the lack of PrEP persistence, especially after the first year. Dr. Volk’s presentation of this study can be viewed HERE
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. Landovitz R. Abstract # OAXLB0101
This study (HPTN 083) is a Phase 2b/3 randomized double-blind trial evaluating safety and efficacy of long-acting injectable cabotegravir (CAB) compared to daily oral TDF/FTC for HIV PrEP. The study included 4,566 HIV-uninfected MSM and TGW from Africa, Asia, Latin America and the United States. Subjects were randomized 1:1 to oral CAB +TDF/FTC placebo or TDF/FTC + oral CAB placebo for five weeks. The subjects were transitioned to CAB 600mg IM every 8 weeks or oral TDF/FTC + CAB placebo injections for 148 weeks. The primary endpoints were incident HIV infection and grade 2 or higher clinical and laboratory events. There were 13 infections in the CAB arm and 39 infections in the TDF/FTC arm. Adherence to oral TDF/FTC was very good with 87% of a random subset of participants (n=372) having detectable plasma drug concentrations. Injection site reactions were more common in CAB participants and resulted in discontinuation by 2% of recipients. Although both CAB and TDF/FTC were safe and highly effective for PrEP, CAB was superior to TDF/FTC with a 66% lower risk of HIV infection. The blinded portion of this trial was stopped at the recommendation of the interim DSMB review in May 2020.
Commentary: The findings of this study are quite significant and IM cabotegravir may represent the future of PrEP if this product ultimately gains FDA approval. I would encourage you to view the full presentation of this study by Dr. Landovitz.