New research was presented at IAS 2021, the virtual 11th International AIDS Society Conference on HIV Science, from July 18-21. The features below highlight some of the studies that emerged from the conference.
HIV Increases Risk for Severe COVID-19
To determine if people with HIV have worse outcomes from COVID-19 when compared with those without HIV, researchers from the WHO Clinical Platform conducted an investigation of 268,412 people hospitalized with COVID-19 from 37 countries, mainly South Africa; of those, 22,640 people were from the US. The study team found that people with HIV—as with those without HIV—older people, men, and people with diabetes, hypertension, or obesity had the worst outcomes from COVID-19 and were most likely to die from the virus. HIV increased the risk for severe COVID-19 by 6% and the risk of dying of COVID-19 in the hospital by 30%. They also discovered that effective treatment for HIV lead to undetectable viral loads, which when maintained for 6 months or more, eliminated transmission of HIV to sexual partners. However, some critical information was not addressed by the study, including the impact on outcomes of T-cell counts or rates of viral suppression. “We know that in South Africa, over 90% of people receiving antiretroviral therapy are virologically suppressed,” a study co-author stated. “So, we could speculate that this effect persists, despite the use of antiretroviral therapy, in a population likely to be virally suppressed, although we cannot be certain based on this data set.”
PrEP Rollout Programs Need to Screen for Acute Infections
For a study from the Global Evaluation of Microbicide Sensitivity (GEMS) project, researchers sought to discover how rates of HIV development among patients who had been prescribed pre-exposure prophylaxis (PrEP) but had drug-resistant HIV. The study was conducted in real-world settings as national PrEP programs were rolled out in several countries. The tesearchers found that breakthrough infections occurred in a subset of 204 individuals in GEMS, out of more than 140,000 people, and many of those in the subset had mutations resistant to antiretroviral drugs. Of those experiencing breakthrough infections, 175 gave blood samples for analysis, among which 104 were genotyped, with at least one HIV drug-resistant mutation detected in 47 (45%) of that subgroup. “Although the number of reported infections of PrEP was very small compared with the total number of PrEP users, these findings reinforce the need for PrEP rollout programs to screen for acute infections before starting people on PrEP and to conduct HIV drug-resistance monitoring,” a study co-author wrote in a statement. This is important, according to the study’s authors, because the same drugs used for PrEP are also used for HIV treatment and prevention, and drug resistance could undermine the progress that has been made toward ending the global HIV epidemic.
On-Demand PrEP Vs. Daily Use Among MSM
Researchers seeking to compare event-driven HIV prevention—with which individuals only took medication before and after sex—with daily regimens among men who have sex with men (MSM), reviewed the cases of 520 MSM who selected a daily regimen, 503 who selected an event-driven regimen, and 507 who declined to initiate PrEP. Those initiating PrEP were younger than non-users (age 29 vs 33, respectively) and had higher scores for risk behaviors. At-risk MSM who were unwilling to initiate PrEP acted as a control group. The authors followed up with participants every 3 months for up to 12 months. During the follow-up period, all PrEP users had a relative reduction of 87% in HIV infection, while adherent PrEP users experienced 100% risk reduction. Incidence rates of HIV infection were lowest among event-driven PrEP users (0.37 per 100 person-years), followed by daily PrEP users (0.90 per 100 person-years), and they were unsurprisingly higher among PrEP non-users (5.10 per 100 person-years). A study co-author noted that PrEP can reduce HIV risk among MSM in a real-world setting, with event-driven PrEP offering “a better HIV protective effect.”
Long-Acting Lenacapavir Shows Viral Suppression at 26 Weeks
The phase II/III CAPELLA trial was conducted to assess the efficacy and safety of lenacapavir, a first-in-class capsid inhibitor. The study showed that, after 26 weeks, 81% of heavily treatment-experienced people with HIV in a randomized cohort who were treated with a subcutaneous injection of lenacapavir combined with an optimized background antiretroviral regimen achieved sustained virologic suppression, with an undetectable viral load (< 50 copies/mL). Lenacapavir-treated patients also achieved a clinically meaningful mean increase in CD4 counts of 81 cells/μL throughout the 26 weeks. the study investigators found that the drug was well-tolerated, with no drug-related serious adverse events or adverse events leading to discontinuation. “With regulatory approval, lenacapavir could become the only HIV-1 treatment option given every 6 months,” the study’s lead author said in a statement “These data support the use of lenacapavir in patients with multidrug-resistant viruses, and according to its long half-life of two subcutaneous injections per year, it could help reduce pill burden.” He added that providing a drug administered every 6 months subcutaneously offers an ideal treatment for overcoming resistance and lack of adherence to an HIV treatment regimen.
Dose Adjustment in BPaL Regimen for TB Benefits Patients With HIV
As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of tuberculosis (TB). However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption. Researchers who sought to examine if lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) could reduce adverse effects associated with the treatment for patients with highly drug-resistant TB, without affecting its high efficacy, found that adjustments in the dose substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in treatment efficacy. They also observed that results were similar among both patients with and without HIV. This is noteworthy, they said, because TB is the leading cause of death among patients with HIV. “These are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” a study co-author said in a statement.