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Rachel Lutz

Progression to anal cancer in HIV patients is 57 percent lower when a patient is involved in HSIL (or precancerous growths) treatment compared to active monitoring, according to a 

Investigators from the University of California, San Francisco School of Medicine randomized 4446 participants living with HIV aged 35 years or older in a phase 3 trial across 25 US cities in order to determine any related effect on treatment for anal high-grade squamous intraepithelial lesions (HSILs), as they noted anal cancer incidence is higher among HIV patients compared to the general population. The study authors said that data gathered from prospective studies based on treatment for anal HSIL to prevent anal cancer have so far been lacking. They also added that HSILs precede cancer, similar to the prognosis of cervical cancer.

The patients were randomized into groups that either received HSIL treatment—which included office-based ablative procedures, ablation, or excision under anesthesia, or topic administration of fluorouracil or imiquimod—or active monitoring without treatment. The patients in the intervention group were treated until HSIL was completely resolved, the study authors said, and all patients underwent high-resolution anoscopy at least every 6 months. The study participants also underwent biopsy; for the intervention group, that was performed for suspected ongoing HSIL. For the control group, biopsy was performed annually or any time there was a cancer concern, the study authors explained.

The investigators found 9 cases in the treatment group after a median follow-up of 25 months, they said, compared to 21 cases in the active-monitoring group. They determined that the rate of progression to anal cancer was lower in the treatment group compared to the active monitoring group by 57 percent.

“We’ve now shown for the first time that treating anal HSIL is effective at reducing the incidence of anal cancer in a very high-risk group of people — people living with HIV,” study leader Joel Palefsky, MD, said in a 

The study authors continued by saying they believe these findings could lead to changing the standard of care for other groups who are at a lower, but still increased, risk for anal cancer. This includes HIV-negative men who have sex with men, women who have had human papillomavirus (HPV) -related precancers or cancers, and people who are immunosuppressed after organ transplant or for other reasons.

“Although we did show a statistically significant reduction in anal cancer due to treatment, we did not prevent all the cases of cancer,” Palefsky added, but noted that the data supports treating HSIL as the standard of care for HIV patients aged 35 years or older. “What that points to is a need for ongoing follow-up of everybody who has developed anal HSIL, even if they’ve been treated, as well as for improvements in the treatments that we use.”

One reason the study authors noted their trial was successful was due to the level of training the participating clinicians received for high-resolution anoscopy and in treating HSILs. The results may not be replicated by other teams if the treatments are performed by clinicians with less training and clinical support, they wrote, which further highlights the need for more training for more clinicians.

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In a phase 3 trial, if HIV patients received treatment for precancerous HSILs, their risk for developing anal cancer was reduced by half. 

Treating HIV Patients’ Precancerous Growths Reduces Anal Cancer by Half

Combination therapy with 2 HIV-specific broadly neutralizing anti-HIV antibodies (bNAbs) may be a future alternative for those with HIV instead of daily antiretroviral therapy (ART), according to a 

Investigators from National Institute of Allergy and Infectious Diseases (NIAID) conducted a 2-comopnent clinical trial in order to determine the ability of 2 HIV-specific bNAbs (3BNC117 and 10-1074) to act as long-acting antiviral agents that inhibit viral replication in HIV patients.

The first part of the study involved a randomized, double-blind, placebo-controlled trial for 14 patients in the acute and early phases of HIV infection who were enrolled in ART. Between September 2018 and January 2021, the patients were taken off ART before their first infusion of bNAbs or placebo. They were given 2 infusions in the first month and once per month thereafter for a total of 8 infusions over 24 weeks. The investigators measured the patients’ CD4 T-cell counts and HIV levels every 2 weeks, they noted.

The study authors found that none of the 7 total patients who received combination therapy had to restart ART before 28 weeks post-infusion compared to 6 of the 7 patients who received placebo. Median time off ART was 39 weeks for the bNAbs group and 9 weeks for the placebo group, the study authors noted in a 

In the second part of the study, 5 ART-naïve HIV patients were enrolled in an open-label, single-arm trial. At the end of the study period, 2 of the 5 patients maintained complete suppression of the virus for an average of 41 weeks, the study authors reported.

If the participants had a resistant HIV strain, the study authors found the bNAbs combination therapy to be ineffective. They warned that antibody-resistant HIV is a threat to effective therapies going forward.

“Our data demonstrate that combination therapy with broadly neutralizing monoclonal antibodies can provide long-term virological suppression without antiretroviral therapy in individuals with HIV, and our experience offers guidance for future clinical trials involving next-generation antibodies with long half-lives,” the study authors wrote.

The study authors wrote that infusions of 3BNC117 and 10-1074 were well-tolerated without any serious adverse events related to the infusions. The investigators noted that is essential for larger studies to confirm their findings, as their studies were conducted with admittedly small sample sizes. Their total number of infusions was also limited to 8, which could be further investigated in larger trials, too.

“As the next generation of bNAbs with increased breadth and prolonged half-lives (>60 days) become available, there is a reason to believe that the infrequent administration (that is, twice a year) of such antibodies, possibly along with a long-acting injectable antiretroviral drug, could lead to ART-free HIV suppression for extended periods (years) in individuals with infection,” the study authors concluded.

This small study had 2 phases, but patients saw HIV viral suppression for about 40 weeks after receiving the combination therapy infusions. 

Combination bNAbs Therapy Could Eventually Replace Daily ART


HIV treatment should not increase the risk for cardiovascular events among patients who are already vulnerable, such as the case with integrase strand-transfer inhibitors (INSTIs), according to a 

Investigators from Denmark used data from an existing large-scale, prospective, observational study in order to determine whether exposure to INSTIs is associated with an increased incidence of cardiovascular disease. It has already been suggested that INSTI use can contribute to weight gain or metabolic syndrome, which in turn can lead to cardiovascular disease, the study authors explained. But INSTIs remain a recommended first-line treatment in North American and European guidelines because of their ability to successfully suppress HIV viral loads, they added.

Among 17 existing European and Australian cohorts, the study authors identified 29,340 HIV-positive individuals with a median age of 44 years, of which 25 percent were female, 74 percent were male and 1 percent were trans. In terms of race and ethnicity, the study authors said 70 percent of participants were white and 10 percent were Black. About half of the patients were exposed to INSTIs during the median 6 years of follow-up and the study authors categorized those patients as:

24 percent were exposed to cobicistat-boosted elvitegravir

During the follow-up period, the study authors found that 2.5 percent of patients (748 patients) experienced cardiovascular disease, with 299 individuals having myocardial infarctions, 228 having strokes, and 221 having invasive cardiovascular procedures. The study authors determined a crude incidence rate of 4.67 events per 1000 person-years of follow-up.

The crude incidence rate for cardiovascular disease increased from 4.19 events per 1000 person-years of follow-up in patients with no INSTI exposure to a peak incidence of 8.49 events per 1000 person-years of follow-up at more than 0 months to 6 months of INSTI exposure, but then gradually decreased to similar rates among those found with no INSTI exposure after 24 months of no exposure, the study authors wrote.

Interestingly, traditional cardiovascular disease risk factors (smoking, hypertension, dyslipidemia, chronic kidney disease, diabetes) were more prevalent at baseline among those who had a cardiovascular disease event during the follow-up period, the study authors determined. Those individuals who had a cardiovascular disease event tended to be older than those without an event, and their 5-year estimated risk of cardiovascular disease at baseline was consequently higher, the study authors noted.

The investigators did not have the statistical power to look at each cardiovascular event in detail, but noted that the crude incidence rate for myocardial infarctions, strokes, and invasive cardiovascular procedures were consistent with the primary analysis. They were also unable to separate ischemic from hemorrhagic strokes when looking at the 34 of 228 strokes caused by cerebral hemorrhages.

“With cardiovascular disease remaining a common cause of morbidity and mortality among people living with HIV, treatment given to suppress HIV must not add to the cardiovascular risk profile,” the study authors concluded. “Therefore, insights into cardiovascular disease risk factors, including the potential role of individual antiretroviral agents, remain crucial. Our results call for investigations in other large studies and further exploration of potential mechanisms underlying the increased relative cardiovascular risk we found here.”

INSTIs have been thought to contribute to weight gain and metabolic syndrome, which in turn may contribute to cardiovascular events in HIV patients. 

INSTIs and Cardiovascular Risk for HIV Patients

Regardless of viral load (VL) patients over the age of 10 years and >35 kg who are taking enofovir/emtricitabine or lamivudine/efavirenz (TEE/TLE) to manage HIV can now be switched to tenofovir/lamivudine/dolutegravir (TLD) regimens, according to a new recommendation from the Southern African HIV Clinicians Society.

For adults, the new recommendation includes switching patients to TLD from a first-line regimen containing an NNRTI (either EFV or NVP), the authors noted. This was true regardless of suppressed or unsuppressed VL or regardless of whether there is a recent VL result, they noted. Additionally, patients who were formerly on a regimen of EFV or NVP and were interrupted, they can be restarted on a TLD.

The guidelines also recommend that adults can switch to a DTG from a second-line boosted PI-containing regimen if they are patients have had any 2 NRTIs + LPV/r or ATV/r who have a VL <50 copies/mL in the last 6 months can switch to TLD. Patients should continue to be managed per the current guidelines, the recommendation states, if they are on LPV/r or ATV/r-based regimens with a VL >50 copies/mL.

For children, the guidelines categorize treatment recommendations into 3 categories. First, children aged greater than 10 years and who weigh > 35 kg can be treated as adults. The guidelines also suggest that adolescent patients who are transitioning from ABC-based first-line regimens can be moved to TLD, regardless of VL.

All children who weigh between 20 and 35 kg and who are on ABC/ 3TC/ EFV who have VL <50 copies/mL in the last 6 months can switch to ABC/ 3TC/ DTG, the guidelines suggest. Patients in this weight class on ABC/ 3TC/ EFV who have VL >50 copies/mL for whom a regimen switch is necessary, should switch to AZT/ 3TC/ DTG with repeat VL at 3 months. Additionally, patients who are on ABC/3TC plus LPV/r or ATV/r with a VL <50 copies/mL in the last 6 can switch can switch to ABC/3TC/DTG, the guidelines said. Finally, patients should continue to be managed per standard South African National Department of Health guidelines if they are on LPV/r or ATV/r-based regimens with a VL >50 copies/mL in the previous 6 months.

And for children who weigh less than 20 kg are not currently eligible for DTG 50 mg tablets, unless recommended by an expert opinion, according to the guidelines.

If patients switch to DTG and continue with an unsuppressed VL, they should be considered for additional support, the recommendation continued. This additional care would be to identify any potential causes for this increased VL such as drug-drug interactions or poor drug absorption, they said.

All of these recommendations have been made with the assumption that there are no contraindications to DTG or TLD, the guidelines noted. The authors also noted that “first-line” and “second-line” terminology will becoming increasingly confusing, a topic that the WHO is currently addressing. But during this period, the authors noted, this terminology will continue to be the standard.

“Since this recommendation was first made, evidence from several trials (NADIA, VISEND and ARTIST) has been published or presented, that demonstrates that tenofovir with lamivudine can be safely and effectively recycled from a first- to a second-line regimen,” the authors wrote.

The South African National Department of Health has updated their HIV regimen recommendations for patients aged older than 10 years and more than 35 kg. 

Recommendation to Use Dolutegravir-Based Regimens for First- and Second-Line ART

In order for access to preexposure prophylaxis (PrEP) to remove its over-reliance on Section 340B of the Public Health Services Act, changes to access for HIV care and PrEP need to be adopted, according to an 

Authors from Harvard Medical School wrote a perspective detailing why less than a quarter of the 1.2 million people eligible to take PrEP to reduce HIV infection are taking the medication. They began by acknowledging that until 2021, PrEP medications cost between $1200 and $1900 per month. After a congressional investigation, generic PrEP medications are available for $21 per month, the perspective authors noted, which is a benefit to patients in terms of access as well as health care cost savings. Despite this, the authors said, a more expensive medication, emtricitabine 200 mg/tenofovir alafenamide 25 mg, is being prescribed which is an unexpected downside of the 340B Drug Pricing Program.

Section 340B of the Public Health Service Act was enacted by congress in 1992, the authors said, and requires drug manufacturers to make discounted medications available to health centers that serve uninsured and low-income patients. As the authors explained, insurers reimburse 340B facilities for their medications near their list price which generates revenue known as the 340B spread that clinics can put towards other health services. When the price of the drug is high, the spread increases, too, the authors noted.

For emtricitabine 200 mg/tenofovir alafenamide 25 mg, for example, and another PrEP, emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg, 340B clinics are paying between $300 and $800 for a one-month supply of those medications. That can produce a monthly spread of as much as $1,600 per patient, the study authors said. The clinics can fund important health services through this revenue, the authors noted, but said “there are unintended consequences of a system that’s so dependent on high drug prices to sustain itself.”

This effect reveals itself in a variety of ways, the authors argued:

When clinics that are not 340B entities, they are left with limited financial options for uninsured or low-income patients. While yes, the 340B program has generated revenue and innovation in the HIV-prevention space, the gaps that remain leave patients that may not seek care at traditional health centers vulnerable due to a variety of stigma or structural barriers to care.

“But pockets of innovation—concentrated among well-financed providers—do not translate into the easy-access approach to PrEP that’s needed to address widening disparities in use,” the authors wrote.

Clinics are incentivized to prescribe high-cost medications even when generic medications, that are cheaper and as effective, are available. The pressure to prescribe the high-cost, brand-name medication may indirectly influence prescribers’ medication choices as well as the patients’ views that generics or another brand-name drug are inferior.

“In a national cohort of mainly gay and bisexual men, 32 percent of PrEP users who switched to [emtricitabine 200 mg/tenofovir alafenamide 25 mg] were motivated by the perception that it’s safer than [emtricitabine 200 mg/tenofovir
disoproxil fumarate 300 mg], whereas only 6% reported having a clinical reason for switching,” the authors wrote.

The authors realized that sweeping changes to 340B may threaten to destabilize the entire system, but that some changes could be implemented to safeguard prescribing practices. For example, the federal government could negotiate fair prices for PrEP medications and labs for the uninsured or Medicaid beneficiaries and could build a network of PrEP providers. This plan, they noted, has been endorsed by President Biden and would allow for PrEP medication disbursement to be based on clinical evidence and not on the “spread” incentive.

“Although 340B will continue to facilitate access to discounted drugs, a national PrEP program would ensure that overreliance on 340B does not dictate clinical decision making,” the authors concluded. “A decade after the emergence of PrEP as a powerful HIV-prevention tool, it’s time to ensure widespread availability by promoting access to safe, effective, and sustainably priced medications, rather than providing incentives to prescribe higher-cost alternatives.”

“It’s time to ensure widespread availability by promoting access to safe, effective, and sustainably priced medications, rather than providing incentives to prescribe higher-cost alternatives,” the authors said. 

An Unintended Consequence for High HIV Drug Prices 


Those who were newly diagnosed with HIV had a low uptake of receiving the recommended meningococcal A, C, W, Y (MenACWY) vaccine, according to an 

A team of investigators from around the United States retroactively identified more than 1200 individuals with newly-diagnosed HIV in order to determine how many newly-diagnosed people with HIV received the recommended MenACWY vaccination. The study authors noted that people infected with HIV are at a 4.5- to 12.9-fold increased risk of meningococcal disease compared to an otherwise healthy population. Additionally, they noted that the US Advisory Committee on Immunization Practices unanimously passed the recommendation that MenACWY be given to people with HIV infection in a 2-dose series.

In their study, the investigators identified 1208 people with a new diagnosis of HIV who were eligible for the MenACWY vaccine. Their mean age was 38 years, though most were between 19 and 55 years, the study authors said, and the majority (nearly 85 percent) were male. The participants had a diverse race and ethnicity makeup, the study authors said.

The study authors checked in at the 12, 18 and 24 months post-HIV diagnosis and found that vaccine uptake was 10.6 percent, 12.9 percent, and 16.3 percent, respectively (those that had received 1 or more doses). There were 71 individuals who received a first dose and had 12 months’ worth of follow-up data, the investigators said; of those, two-thirds received the second dose within a year of the first.

When breaking down the age groups, the study authors noted that those aged 2 to 13 years had an uptake of about 30 percent, compared to those 19 to 55 who had 13 percent, and those over 56 years of age had a 4 percent rate of vaccine uptake.

There was also a wide range of clinician types who administered the vaccine, the study authors observed. A quarter of vaccines were administered by an infectious disease specialist, followed by 20 percent being internal medicine, 17 percent primary care, and 3 percent pediatrician, with the remainder being other specialists (30 percent) and unknown. Only about 10 percent of vaccinations were given at well-care visits, the study authors wrote. All 4 children between the ages of 11 to 18 received their vaccines from pediatricians.

Receipt of pneumococcal vaccine, attendance at a well-care visit, male sex, and West or Midwest geographic location were all factors statistically significantly associated with receiving the MenACWY vaccine, the study authors said. The age 56 years or older and baseline emergency department visits were statistically significantly associated with a reduced incidence of vaccine uptake, though, the study authors said.

“Only 16.3 percent of retrospectively identified people with a new diagnosis of HIV were estimated to have received the MenACWY vaccine during the 24 months after their diagnosis,” the study authors wrote. “Uptake of a second dose of the MenACWY vaccine was considerably higher than uptake of a first dose, perhaps because people who received an initial vaccination were visiting clinicians who are more likely to vaccinate in general and/or indicating that people with HIV are more likely to complete a vaccine series than to start it.” 

People infected with HIV are at a 4.5- to 12.9-fold increased risk of meningococcal disease compared to an otherwise healthy population, the study authors said. 

Rachel Lutz

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