No evidence of transmitted TDF/FTC resistance was found in patients prescribed PrEP who acquired HIV infection. Pre-exposure prophylaxis for HIV (PrEP) with tenofovir-emtricitabine reduces the transmission of HIV infection between serodiscordant sex partners. Some clinicians, however, have expressed concern that PrEP use could lead to increased transmission of HIV viruses resistant to tenofovir and emtricitabine (e.g. carrying mutations M184V or K65R), which would be a big deal given that those two drugs are the backbone of many, perhaps most, antiretroviral regimens across globe.
However, the actual risk of transmitting these resistances seems negligible. This welcome news come from an analysis of patients who developed HIV infection during the IPERGAY ANRS trial, which demonstrated the efficacy of tenofovir disproxil fumurate (TDF) and emtricitabine (FTC) for the prevention of HIV transmission in highly exposed men who have sex with men. The authors took frozen plasma samples from the 31 participants diagnosed with HIV infection either at study entry or during the trial and performed sequencing of the viral reverse transcriptase. Six participants had virus with RT mutations conferring resistance to either an NRTI (zidovudine) or NNRTIs, but no TDF or FTC-associated resistance mutations were detected. One explanation for the lack of transmitted resistance is that the patients prescribed PrEP who acquired HIV infection acquired their infections on account of not being on medication, meaning there was no drug to exert selective pressure for the (generally less replication-competent) resistant viruses. 30096070
Here’s a small cohort study to comfort us about using doxycycline to treat syphilis in people with HIV infection. The authors report their experience treating syphilis in HIV-infected patients during a benzathine penicillin shortage, comparing their outcomes with doxycycline versus penicillin for early, late latent, and latent of unknown duration syphilis. Over a two-year period, 50 patients received doxycycline and 115 patients received benzathine penicillin (all for standard durations for the type of syphilis being treated). Doxycycline recipients were slightly older and had a lower median CD4 count (542 versus 617 cells/ul in the penicillin recipients). Otherwise the groups were similar, and overall 95% of the cohort was on antiretroviral therapy, with 83% having achieved an undetectable viral load. Response to therapy, defined as a negative VDRL or >4-fold reduction in VDRL titer measured 6-12 months after antibiotic treatment, occurred in 70% of the cohort and did not differ by antibiotic used (70% for penicillin versus 72% for doxycycline). No difference was noted after multivariate adjustment for age and CD4 count.
This is a small study, and importantly did not include cases of neurosyphilis, but it’s nice to know about for that occasional patient in HIV clinic who’s been diagnosed with late latent syphilis and absolutely refuses to return for his or her 2nd and 3rd shots of penicillin. 30102654
Switching from efavirenz or ritonavir-boosted protease inhibitor based regimens to a rilpivirine-based regimen improves lipid profiles. I am an unapologetic fan of rilpivirine (RPV). Yes, guidelines recommend that it should only be used in patients with a CD4 count >200 cells/ul and an HIV viral load <100,000 copies/ml, which is based on RPV’s lower rates of viral suppression versus efavirenz (EFV) in patients with higher viral loads in the ECHO and THRIVE trials that lead to RPV’s approval. However, subsequent studies demonstrated that switching EFV to RPV is safe in patients who have achieved viral suppression, and that’s where I see RPV’s role in the modern antiretroviral armamentarium. Given its benign side effect profile, daily dosing, and few med interactions, RPV (coformulated with either dolutegravir or tenofovir alafenamide and emtricibine) can be a great switch option for patients who’ve achieved viral suppression on more complicated or toxic regimens.
Here’s one more reason to like switching to RPV: potential cardiovascular benefit. This study used data from a long-term surveillance cohort of people living with HIV infection (the SCOLTA database) to evaluate the effects on lipid profile of switching from an EFV or ritonavir-boosted protease inhibitor (PI/r) based regimen to either an integrase inhibitor or RPV based regimen. A total 490 subjects met the study criteria, including 242 who switched to a RPV-containing regimen. Switching either EFV or PI/r to RPV resulted in significant reductions in LDL (-21 mg/dl for EFV and -13.6 mg/dl for PI/r), triglycerides (-31.5 mg/dl for EFV and -28.2 for PI/r), and total cholesterol (-31.6 mg/dl for EFV and -20.7 mg/dl for PI/r) over a one-year period. HDL levels modestly decreased when switching EFV to RPV (-2.9 md/dl; p=0.042) but not when switching PI/r to RPV. Switching to INSTI-based regimens provided some of these benefits in some cases, but generally to lesser degrees. Detectable HIV viremia occurred following switch in 18/490 patients, and the majority of viremias were <1000 copies/ml.
Once a person living with HIV has managed to suppress their viral load, cardiovascular disease becomes one of the diseases most likely to eventually kill them, so anything we can do to limit a HIV-infected patient’s cardiovascular risk is worth considering. If your clinic panel includes one of these 65-year-old men with hypertension, dyslipidemia and HIV infection controlled for years on EFV/TDF/FTC, consider having a conversation about switching them to rilpivirine. 30064371
Histoplasmosis may be more common and deadly than tuberculosis among people with HIV infection in Latin America. This was a modeling study based on a search of relevant literature. The authors aimed to estimate the incidence of histoplasmosis exposure, disease, and associated death in Latin Americans with HIV infection, identifying 24 papers on the topic. They then compared these estimates to WHO data on the burden of tuberculosis in the same region. They estimate that 6700-15600 cases of histoplasmosis occur in Latin American patients with HIV infection annually, accounting for 600-9300 deaths each year. This potentially exceeds the estimated 5062 annual deaths attributed to tuberculosis.
Why does this matter? Not only is histoplasmosis notoriously difficult to diagnose, but its clinical presentation in patients with HIV infection and low CD4 counts closely mimics that of tuberculosis and/or disseminated MAC. So, if we don’t start out considering histoplasmosis in these patients, we’re likely to miss it. 30146320