June 2018: HIV and STDs

For people with HIV infection, viral suppression with ART = cancer prevention, both for AIDS-defining cancers and other cancers caused by viruses, and longer durations of suppression are more protective. This retrospective multicenter VA study compared the incidence of a wide variety of cancers in veterans with vs without HIV infection, stratified by whether the patient had HIV infection  not suppressed on ART, had become suppressed within the past 2 years, had been suppressed for more than 2 years, or did not have HIV infection.

The authors found that, relative to the uninfected controls, the incidence of cancer was greatest in HIV patients without viral suppression (RR 2.35), then those who only recently achieved suppression (RR 1.99), and was lowest among those with long-term suppression (RR 1.52). The increased risk was dramatic for AIDS-defining cancers (unsuppressed RR 22.73; early suppression RR 9.48; long-term suppression RR 2.22), and modest for other caused by other viruses (unsuppressed RR 3.82; early suppression RR 3.42; long-term suppression RR 3.17). There was no association between HIV control and cancer risk for non-AIDS defining cancers not caused by viruses. Disclaimer: Dr. Maria Rodriguez-Barradas, a co-author of this study, is one of my mentors. PMID: 29893768

Do you send your patients with well-controlled HIV for low-dose CT screening for lung cancer? I haven't been doing this, but perhaps I should. This practice has been endorsed by multiple societies for patients 55-77 years of age who have at least a 30 pack-year smoking history and who either still smoke or quit within the past 15 years; however, there is no specific screening recommendation for people living with HIV. This modeling study suggests that in people with HIV infection who have a CD4 count of at least 500 cells/ul and who are 100% adherent to ART, screening would decrease lung cancer-attributable mortality by 18.9%, similar to the benefit gained by people without HIV infection. PMID: 29683843

Pharmacokinetic data suggests PrEP might be less efficacious in women who are pregnant. Specifically, this study looked at levels of tenofovir disproxil fumurate and its metabolite tenofovir diphosphate in 37 pregnant and 97 nonpregnant women receiving PrEP. They found that tenofovir DF levels were 58% lower in the pregnant women (not significant after adjustment for confounders) and tenofovir diphosphate levels were 27% lower (which was significant). There is no established minimum tenofovir concentration for preventing HIV infection, but this study makes me nervous about PrEP in pregnancy, particular because recent data suggests the HIV transmission risk increases continuously throughout the stages of pregnancy. Until there's more data, even in the absence of concern re: other STIs (e.g. a monogamous serodiscordant couple not falling under U=U) I think I would strongly encourage a pregnant woman to consistently use barrier protection with sex in addition to taking PrEP. PMID: 29894385

Protease inhibitor therapy may be a risk factor for osteopenia and osteoporosis, particularly in older women with HIV infection. So says this retrospective study of people with HIV infection who were stratified by whether their regimens contained tenofovir, a PI, both, or neither. For men, darunavir carried particularly elevated risk; for women, that was true of both darunavir and atazanavir. One more study for me to quote when my co-fellows make fun of me for liking rilpivirine so much. PMID: 29860519 

Darunavir has been associated with increased cardiovascular risk. This was an international prospective cohort study including 35,711 patients with HIV infection treated with either darunavir-ritonavir or atazanvir-ritonavir. The patients were followed from 2009 until either 2016 or their first cardiovascular event, which was defined as a composite outcome of sudden cardiac death, myocardial infarction, stroke, or need for an invasive cardiovascular procedure such as cath, CABG, or carotid endarterectomy. After adjustment for confounding factors, receipt of darunavir-ritonavir was associated with an increased risk of cardiovascular events, which increased with more prolonged use of darunavir-ritonavir (IRR 1.59 per 5 years of use).

Association is not causation, but until more data is available, these findings leave me hesitant about sticking with darunavir-ritonavir for antiretroviral therapy in patients with coronary artery disease or CV risk factors. We're living in an age where we have multiple options for high barrier to resistance ART regimens, including dolutegravir, bictegravir, and soon doravirine, so we ought to be able to find alternative regimens. PMID: 29731407

Two HIV regimen switch studies published this month demonstrate the safety of switching to BIC/TAF/FTC (Biktarvy) from either PI-based or dolutegravir-based regimens. One study looked at switching patients from a regimen of two NTRIs plus either boosted atazanvir or boosted darunavir to BIC/TAF/FTC, and the other looked at switching from DTG/ABC/3TC (Triumeq) to BIC/TAF/FTC. No surprise, both switches were safe and fairly well-tolerated when compared to keeping patients on their prior regimen. A significant number of patients in the switch arm of the PI study reported drug-related adverse events (19%), which was not the case in the DTC/ABC/3TC switch study. This shouldn't surprise us much: bictegravir is in the same class as and structurally very similar to dolutegravir, so people already tolerating DTG/ABC/3TC were likely to do well on BIC/TAF/FTC.

Bictegravir has a high barrier to resistance and is coformulated with tenofovir alafenamide, which is the new and better tolerated form of tenofovir, as well as emtricitabine. This makes for a highly effective and high barrier to resistance single tablet regimen with few side effects or major drug interactions and little resistance in the community. Right now BIC/TAF/FTC is looking like a great option to start or switch to for most patients with HIV infection. The most common scenarios in which BIC/TAF/FTC may not be a good choice include rifampin/rifabutin treatment for TB (because tenofovir AF interacts with rifamycins), advanced renal disease, and resistance to one or more of the drugs included in BIC/TAF/FTC. Until we have more information, I'd also think twice about starting it in someone who is pregnant or likely to become so, given that use of bictegravir's sibling dolutegravir during pregnancy has been associated with neural tube defects – but to be clear, I’m not aware of any FDA or other official guidance to that effect for bictegravir. PMIDs: 29925490 and 29925489