In October 2019, the US Food and Drug Administration approved a second medication for use as HIV preexposure prophylaxis, also known as PrEP, sparking controversy about which drug should be prescribed. Gilead Sciences, which manufactures both approved drugs, has argued that the new drug is safer and more effective than the old drug. But these claims are overstated, say a team of clinical and public health experts.

Their commentary, “Tenofovir Alafenamide for HIV Preexposure Prophylaxis – What Can We DISCOVER About Its True Value?”, appears in the January 14 issue of Annals of Internal Medicine.

PrEP, which is 99% effective in preventing HIV, exists in two forms: tenofovir disoproxil fumarate with emtricitabine (TDF/FTC) – best known as Truvada, its brand name in the US – and tenofovir alafenamide with emtricitabine (TAF/FTC), known as Descovy. TDF/FTC has been used for PrEP for more than 7 years, with ample evidence of its safety and effectiveness.

“These drugs are equally effective when used for PrEP in gay and bisexual men and transgender women, and the potential safety benefits of TAF/FTC over TDF/FTC have not yet been shown to be clinically significant,” said lead author Douglas Krakower, MD, Assistant Professor at the Harvard Pilgrim Health Care Institute, Beth Israel Deaconess Medical Center, and Harvard Medical School.

The high cost of PrEP medications, around $24,000 per year in the US, has been a major barrier to PrEP use. Activists have argued that taxpayer money funded the development of PrEP medications, and the US Department of Health and Human Services recently sued Gilead Sciences over patent infringement.

The older PrEP medication, TDF/FTC, will be available as a generic as early as 2020, which could reduce costs and increase access. But Gilead Sciences holds the exclusive rights to manufacture TAF/FTC until 2022 and has requested a patent extension to 2025. If the generic version of TDF/FTC is perceived to be less safe, uptake of TAF/FTC would presumably rise – with cost ramifications.

“With the exorbitant cost of these drugs, there are huge public health and economic implications if most PrEP users begin to use the newer TAF/FTC pill rather than TDF/FTC for PrEP,” said senior author Julia Marcus, PhD, Assistant Professor in the Department of Population Medicine at Harvard Pilgrim Health Care Institute and Harvard Medical School. “Gilead is asking us to ‘update’ our PrEP to TAF/FTC, but that’s not a clinically necessary or cost-effective choice for the vast majority of PrEP users.”

The authors examined the available data on the safety, efficacy, and public health context for the two PrEP medications. Robust data show the effectiveness of TDF/FTC in all priority populations at risk for HIV, including gay and bisexual men, transgender women, people who inject drugs, and heterosexuals whose partners are living with HIV. In contrast, the only efficacy data for TAF/FTC come from the DISCOVER trial, which enrolled solely gay and bisexual men and a small number of transgender women.

“In the DISCOVER study, TDF/FTC was associated with small changes in renal and bone biomarkers, while TAF/FTC was linked to weight gain and changes in cholesterol,” noted Dr. Krakower. But there were no differences between the groups in clinical events or the number of people who stopped the drug for safety reasons, suggesting that these small changes may not be clinically important. “Given the available clinical evidence and public health context, TDF/FTC should remain the first choice for the vast majority of PrEP users,” he said.

In addition to Drs. Krakower and Marcus, authors of the commentary included Demetre Daskalakis, MD, Deputy Commissioner at the New York City Department of Health and Mental Hygiene, and Judith Feinberg, MD, Professor of Medicine at West Virginia University and Chair of the Board of Directors of the HIV Medicine Association.

In August 2019, there were 1,228 newly confirmed HIV-positive individuals reported to the HIV/AIDS & ART Registry of the Philippines (HARP). This was 17% higher compared with the diagnosed cases (1,047) in the same period in 2018.

This is worth noting: The figure is ALSO higher than the month before, July 2019, when the HARP recorded 35 new HIV cases per day.

As of end-August, the Philippines now has 36 new HIV cases per day; up one case in July 2019.

As contained in the still-delayed report of the DOH, 15% of the new cases in August (or 185) had clinical manifestations of advanced HIV infection (WHO clinical stage 3 or 4) at the time of diagnosis.

Ninety-five percent (1,170) of the newly diagnosed were male. The median age was 27 years old (age range: 1-72 years old). Almost half of the cases (47%, 578) were 25-34 years old and 35% (424) were 15-24 years old at the time of testing.

More than a third (34%, 417) were from the National Capital Region (NCR). Region 4A (18%, 218), Region 3 (9%, 117), Region 7 (8%, 93), and Region 6 (7%, 82) comprised the top five regions with the most number of newly diagnosed cases for the month, together accounting for 76% of the total figure.

Sexual contact remained as the predominant mode of transmission (98%, 1,202). Among the newly diagnosed, 61% (748) reported transmission through male to male sex, 25% (310) through sex with both males and females, and 12% (144) were through male to female sex. Other modes of transmission were sharing of infected needles (1%, 13) and vertical (formerly mother-to-child) transmission (<1%, 2). Eleven cases had no data on mode of transmission.

Among the newly diagnosed females this month, nine were pregnant at the time of diagnosis. Five cases were from NCR, two from Region 7 and one case each from Regions 3 and 11.

SPECIAL POPULATIONS

HIV continues to greatly adversely affect the young.

In August 2019, 424 (35%) cases were among youth 15-24 years old; and 97% were male. Almost all were infected through sexual contact (29 male-female sex, 288 male-male sex, 105 sex with both males and females). One case was infected through sharing of needles and one had no data on mode of transmission.

Still for the same period, there were 69 newly diagnosed adolescents (10-19 years old) at the time of diagnosis. Of these, two cases were 10-14 years old, 18 were 15-17 years old, and 49 were 18-19 years old. Almost all were infected through sexual contact (four male-female sex, 48 male-male sex, and 16 had sex with both males and females) and one had no data on mode of transmission. In addition, there were two diagnosed cases less than 10 years old and both were infected through vertical/mother-to-child transmission.

Sixty-three Filipinos who worked overseas within the past five years, whether on land or at sea, were diagnosed in August 2019. They comprised 5% of the total newly diagnosed cases for the month. Of these, 86% (54) were male. All were infected through sexual contact (seven male-female sex, 30 male-male sex, and 17 sex with both males and females). The ages of male OFWs ranged from 21 to 68 years (median: 32 years). Four were 15-24 years old, 27 were 25-34 years old, 22 were 35-49 years old, and one case was 50 years & older. Among the nine female OFWs diagnosed in August 2019, four each were in 25-34 & 35-49 years old age group and one was 50 years and older at the time of testing. The age range among diagnosed female OFWs were 31 to 56 years (median: 35 years old).

The number of those getting infected with HIV from transactional sex is still noteworthy.

In August 2019, 13% (163) of the newly diagnosed engaged in transactional sex. Ninety-eight percent (159) were male and aged from 13 to 72 years old (median: 28 years). Fifty-eight percent (92) of the males reported paying for sex only, 35% (56) reported accepting payment for sex only and 7% (11) engaged in both. Also, among the four female cases who engaged in transactional sex, two were reported to have accepted payment for sex only, one case was paying for sex only and one case had engaged in both paying and accepting payment in exchange for sex.

Meanwhile, and as already stated, nine pregnant women were newly diagnosed with HIV. Five cases were from NCR, two from Region 7 and one case each from Regions 3 and 11. The age of diagnosis ranged from 19 to 36 (median age: 31).

ACCESS TO MEDS

The number of those in ART has FINALLY breached half the total number of PLHIVs.

The first case of HIV infection in the Philippines was reported in 1984. Since then, there have been 70,740 confirmed HIV cases reported to the HARP.

In August 2019, there were 922 patients who were initiated on ART. The median CD4 of these patients upon enrollment was 207 cells/mm. With the 922, a total of 40,952 people living with HIV (PLHIV) were presently on ART as of end-August. Most of whom were males (97%). The age of reported cases ranged from 1 to 81 years (median: 31 years old). Ninety-five percent were on first line regimen, 4% were on second line, and 1% were on other line of regimen.

Still also worth noting is the continuing problem with access to treatment in the Philippines. The DOH itself has been lambasted for its problematic procurement issues that affect ART intake; and this is even if DOH continues to deny that there are issues hounding its HIV-related efforts.

COUNTING DEATHS

But that HIV is no longer a death sentence remains an invalid claim in the Philippines.

In August 2019, there were 70 reported AIDS-related deaths. Ninety-six percent (67) were males. One (1%) were less than 15 years old at the time of death, 16 (23%) cases were 15-24 years old, 30 (43%) were 25-34 years old, 19 (27%) were 35-49 years old and four (6%) were 50 years and older. Eighty-nine percent of the cases were reported to have acquired the infection through sexual contact.

Sexual contact (96%) was the most common mode of HIV transmission among reported deaths (752 through male-female sex, 1,698 through male-male sex, 987 through males who have sex with both males and females). Other modes of transmission of reported deaths were sharing of infected needles (79), vertical/mother-to-child transmission (26),

To stress, the actual number of AIDS-related deaths in the country is questionable because of non- and/or under-reporting.

Women living with HIV who are also pregnant don’t always receive recommended antiretroviral medications, according to a recent study of prescribing patterns carried out by a MassGeneral Hospital for Children (MGHfC) researcher in collaboration with other members of the Surveillance Monitoring for ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) network.

Few studies, if any, have compared actual prescribing patterns of HIV medications for pregnant women to national treatment guidelines. This study suggests that physicians may be prescribing ahead of the published recommendations, and using drugs or drug combinations they have seen work in the adult population in general.

“We studied, more than 1,500 women and found that 30% were prescribed drugs that had insufficient evidence of safety in pregnancy,” says Kathleen M. Powis, MD, MPH, investigator in MGHfC’s division of Pediatric Global Health and first author of the study, which was published in JAMA Network Open.

For the last 25 years, the US Department of Health and Human services Panel on Treatment of HIV-infected Pregnant Women and Prevention of Perinatal Transmission has published Perinatal HIV Treatment Guidelines on prescribing antiretroviral medications (ARVs) during pregnancy. In 1994, the guidelines just addressed the use of zidovudine, then the only drug approved to treat HIV infection. But by 2008 the prescribing guidelines for pregnant women were updated to recommend the use of triple ARVs, regardless of the woman’s HIV disease status. Pregnant women are typically excluded from studies testing newer drugs until safety has been established in nonpregnant adults. As a result, this data is usually some of the last to be collected.

“The guidelines change nearly annually,” says Powis, who is also an assistant professor of Pediatrics at Harvard Medical School (HMS). “And a lot of the treatments that doctors are already using simply had ‘insufficient data’ to recommend their use in pregnant women. But doctors were prescribing them anyway.”

Since many of these regimens (70%) were eventually recommended for pregnant women, Powis suggests that doctors may be prescribing “ahead of time.” That is, they are seeing promising therapeutic results in the general population, and prescribing HIV drug treatment combinations to pregnant women based on that experience, rather than on guidelines.

While early antiretroviral therapy, or ART, has ensured less deadly outcomes for children living with and exposed to HIV, studies show the virus still may affect the brain. HIV may disrupt neurodevelopment, affecting how children learn, reason and function.

That’s why Michael Boivin, professor and director of the Psychiatry Research Program in the Michigan State University College of Osteopathic Medicine, set out to understand exactly how HIV impacts children’s neuropsychological development in a two-year longitudinal study, published in Clinical Infectious Diseases.

The research was supported in part by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Boivin and his colleagues evaluated the neuropsychological development of three groups of children aged 5 to 11: those who acquired HIV perinatally and were treated with ART, those exposed but HIV-negative, and those who were never exposed. The research took place at six study sites across four countries in sub-Saharan Africa for a robust view of how HIV is affecting children in the region.

To date, it’s the first well-validated, multi-site neuropsychological evaluation of African school-aged children affected by HIV.

What the researchers discovered through various assessments was that even in the face of early treatment and good clinical care, there are still significant neuropsychological problems for children living with HIV.

“These children came into the study with a deficit compared to their counterparts,” Boivin said. “It stayed about the same throughout the two years, except in one important area: reasoning and planning. On that specific test domain, the children living with HIV failed to progress over time.”

In other words, the gap between infected and HIV-negative children grew in the planning and reasoning area over the study period. Typically, these abilities tend to blossom in the school-aged years in healthy children.

“This is the most important cognitive function for the future of children living with HIV in terms of their likelihood of taking their medications, making good decisions, abstaining from risky behaviors like early sexual activity, psychosocial issues and school-related achievement,” Boivin said.

The bottom line? Early medical treatment, started as early as 6 months of age, is probably not enough to address the neurocognitive deficits associated with HIV, even though it helps keep children alive and healthier than they would be without treatment. In these children, treatment should be started even earlier to improve long-term neurocognitive outcomes.

“We’re going to have to complement the long-term care and support with actual behavioral interventions,” Boivin said.

That’s something Boivin and his colleagues are already working on. Earlier this year, Boivin received a 5-year, $3.2 million NIH grant to continue his work with children affected by HIV in Uganda and Malawi.

Through this grant, researchers will investigate how MSU-developed computer cognitive games can serve as tools for neurocognitive evaluation, enrichment and potentially rehabilitation.

Boivin hopes that the results of both of these studies will help make this model of neuropsychological evaluation a considered part of the cost benefit of care for kids affected by HIV.

“Often it’s overlooked or seen as an afterthought, but unlike other areas of medical follow up, neuropsychological evaluation really gets at how well the kids are going to adapt and function in school, at home, in the community and in society in general,” Boivin said. “It’s really what links us most directly to the human burden of disease.”

Stigma is an important contributor to the continued HIV epidemic in the United States. While pre-exposure prophylaxis (PrEP) is a medication that can be taken to prevent HIV infection, previous research has shown that a barrier preventing gay, bisexual and other men who have sex with men from using PrEP is fear that partners, family members or community members would believe that those who use PrEP are HIV infected. Less is known, however, about these factors among women.

While women make up nearly one in five of all new HIV infections, PrEP is largely underutilized by women who are at risk for infection and little is known about the role of stigma among women. A new study that includes a team from the University of Pennsylvania School of Nursing (Penn Nursing), the New York Blood Center, and The CUNY School of Medicine at the City College of New York advances scientific knowledge about how stigma about PrEP use may affect whether or not a woman at elevated risk for HIV infection is interested in starting PrEP.

“Advancing our understanding of factors that influence uptake of PrEP among women is a critical goal, given how significantly underutilized PrEP is among women at risk for HIV infection in the United States,” says Penn Nursing’s Anne M. Teitelman, PhD, FNP, FAAN, Associate Professor of Nursing, and one of the study’s investigators. Results of the study “PrEP Stigma, HIV Stigma, and Intention to Use PrEP Among Women in New York City and Philadelphia,” will be published in an upcoming issue of the journal Stigma and Health.

Funded by the National Institutes of Health, the study Just4Us Study surveyed 160 women aged 18-55 years in Philadelphia and New York City, cities which have high HIV infection rates. The researchers used a scale developed specifically for women that includes an item of particular sociohistorical importance to people of color, low-income women and other marginalized groups of women. Higher stigma about PrEP use, but not stigma about HIV, was significantly associated with lower intention to start PrEP among the women who participated in the study.

The study recommends different ways to design behavioral interventions that specifically address PrEP stigma among women. They include:

-Expand public messaging to increase PrEP awareness and knowledge among women; -Include messaging that addresses the role of PrEP stigma and challenges stereotyped beliefs about women PrEP users; and -Design interventions that integrate stigma reduction at the individual and community levels.

“The next steps to address this gap are to use these findings to guide intervention development and to rigorously evaluate these interventions,” said Teitelman.

Co-authors of the study include: Beryl A. Koblin, Bridgette M. Brawner, and Annet Davis, all of the University of Pennsylvania; Deepti Chittamuru, of the University of California Merced; Victoria Frye, of the City University of New York; and Hong Van Tieu, of the New York Blood Center.

Many high-risk people eligible for medication to prevent HIV infection face barriers to obtaining a prescription, according to research by University of Massachusetts Amherst psychologist Avy Skolnik.

Those barriers include knowledge gaps and attitudinal roadblocks among providers and systems, and the placement of responsibility on the patient to request the service – even though it’s typically the role of health care providers to educate patients about preventive care, such as flu shots and cancer screenings.

“This study points to a need for better HIV preventive care,” says Skolnik, lead author of the study published in the Journal of General Internal Medicine and staff psychologist for University Health Services. “Placing the burden on the patient is not quality care.”

For HIV-negative people, a single pill a day can reduce the risk of acquiring HIV by 99%, according to the National Institutes of Health. Skolnik points out that the Centers for Disease Control and Prevention estimates that up to 1.2 million people at risk for HIV could benefit from taking preventive medication known as PrEP (pre-exposure prophylaxis), but less than 6% are accessing it.

Along with colleagues from the Bedford VA Medical Center, Boston University, Case Western University, the VA Boston Healthcare System and the Cleveland Department of Veterans Affairs Medical Center, Skolnik conducted a targeted medical records review during his post-doctoral work at VA Bedford. The researchers wanted to explore possible barriers, in addition to financial, that would help explain the “modest” use of the PrEP pill.

In 2012, the Food and Drug Administration approved PrEP, which consists of emtricitabine/tenofovir, two antiretroviral drugs that are among those used to treat HIV infections. HIV is transmitted mainly through sex or sharing needles for intravenous drug injections.

Veterans constituted an ideal study group because in 2013 the Veterans Health Administration (VHA) agreed to cover the cost of PrEP, allowing researchers to study barriers beyond the financial issues that people with commercial insurance limits may face.

In a retrospective chart review, Skolnik and colleagues mined the medical records of 161 veterans who received PrEP at one of 90 low-, medium- or high-prescribing sites across the country. Some 97% were men whose primary HIV risk factor was having male sexual partners. Skolnik detected “implicit homophobic undertones” in some of the provider notes, such as, “Patient admits to same sex sexual relationship” and “I am not comfortable prescribing for this purpose.”

Other highlights of the findings:

• Patients initiated 94% of PrEP conversations, and 35% experienced delays in receiving PrEP ranging from six weeks to 16 months. “We thought that was striking,” Skolnik says. “Patients had to initiate the self-disclosure involved and also have that conversation multiple times. We don’t expect any other patient to have that level of persistence for any other preventive service.”
• Barriers to access were identified in more than 70% of cases. They included knowledge gaps about PrEP or the VHA system related to PrEP, confusion or disagreement about which provider (primary care or specialist) should prescribe PrEP and attitudes or stigma associated with PrEP.
• Married heterosexuals in monogamous relationships were least likely to experience access barriers.

The study used an algorithm to identify electronic records of patients who were prescribed PrEP. That leaves “two big question marks,” Skolnik says – the cases in which a provider recommended PrEP and the patient declined, and those in which patients asked for PrEP but dropped the matter when they encountered a barrier.

The researchers recommend increased access to PrEP in the primary care setting and educational initiatives to enhance providers’ knowledge about PrEP and address implicit bias to improve care, especially for LGBT veterans and veterans of color.

“The medication isn’t the solution for every patient,” Skolnik says, “but there are barriers to access that should be addressed.”

The study’s recommendations can be applied in other health care settings because the access barriers to PrEP identified inside the VHA are likely to exist in other health care delivery arenas, as well, Skolnik points out.

“These findings can inform targeted approaches that are needed to improve PrEP access to those at risk for HIV infection,” the study concludes.