current issues in the philippines for research paper

Unraveling Economic Challenges: An in-depth Analysis of Issues Facing the Philippine Economy

18 Pages Posted: 21 Feb 2024

Heinrich Villareal

World Citi Colleges - Quezon City - Graduate School Department

Florinda Vigonte

Marmelo v. abante.

Date Written: February 16, 2024

This comprehensive study explores the nuanced perceptions of economic status in the Philippines, delving into the multifaceted dimensions that shape individuals' perspectives across diverse demographic parameters. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the research discerns the intricate interplay between age, gender, education, profession, and geographical location in shaping economic concerns. The findings illuminate distinct economic challenges faced by young professionals entering the job market, retirees managing fixed incomes, and individuals at various career stages. Gender-based disparities underscore the importance of inclusive policymaking, while educational attainment emerges as a pivotal determinant influencing economic outlooks. Profound insights into the impact of the COVID-19 pandemic on specific sectors, coupled with an exploration of historical economic trends and global events, provide a holistic understanding of the economic landscape. The study also emphasizes the critical role of government policies, sustainability considerations, and environmental consciousness in shaping economic trajectories. Despite challenges, the Philippines exhibits economic resilience, supported by positive growth rates and identified opportunities across sectors. Looking forward, collaborative efforts between governments and businesses, focusing on transparency, communication, and private sector engagement, emerge as essential drivers for sustainable economic growth and social progress. The Philippines, with its resilient economy, sustained remittances, and rebounding tourism industry, appears well-positioned for continued progress while navigating challenges such as income inequality and global geopolitical dynamics with strategic considerations.

Keywords: COVID-19 Pandemic, employment, inflation, Philippine economy, policy measures, poverty, PRISMA diagram, public debt, social equity

Suggested Citation: Suggested Citation

Heinrich Villareal (Contact Author)

World citi colleges - quezon city - graduate school department ( email ).

09171327441 (Phone)

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The State of the HIV Epidemic in the Philippines: Progress and Challenges in 2023

Louie mar a. gangcuangco.

1 Hawaii Center for AIDS, John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA

Patrick C. Eustaquio

2 Love Yourself, Inc., Mandaluyong 1552, Metro Manila, Philippines; hp.flesruoyevol@kcirtap

In the past decade, the Philippines has gained notoriety as the country with the fastest-growing human immunodeficiency virus (HIV) epidemic in the Western Pacific region. While the overall trends of HIV incidence and acquired immunodeficiency syndrome (AIDS)-related deaths are declining globally, an increase in new cases was reported to the HIV/AIDS and ART Registry of the Philippines. From 2012 to 2023, there was a 411% increase in daily incidence. Late presentation in care remains a concern, with 29% of new confirmed HIV cases in January 2023 having clinical manifestations of advanced HIV disease at the time of diagnosis. Men having sex with men (MSM) are disproportionately affected. Various steps have been taken to address the HIV epidemic in the country. The Philippine HIV and AIDS Policy Act of 2018 (Republic Act 11166) expanded access to HIV testing and treatment. HIV testing now allows for the screening of minors 15–17 years old without parental consent. Community-based organizations have been instrumental in expanding HIV screening to include self-testing and community-based screening. The Philippines moved from centralized HIV diagnosis confirmation by Western blot to a decentralized rapid HIV diagnostic algorithm (rHIVda). Dolutegravir-based antiretroviral therapy is now the first line. Pre-exposure prophylaxis in the form of emtricitabine–tenofovir disoproxil fumarate has been rolled out. The number of treatment hubs and primary HIV care facilities continues to increase. Despite these efforts, barriers to ending the HIV epidemic remain, including continued stigma, limited harm reduction services for people who inject drugs, sociocultural factors, and political deterrents. HIV RNA quantification and drug resistance testing are not routinely performed due to associated costs. The high burden of tuberculosis and hepatitis B virus co-infection complicate HIV management. CRF_01AE is now the predominant subtype, which has been associated with poorer clinical outcomes and faster CD4 T-cell decline. The HIV epidemic in the Philippines requires a multisectoral approach and calls for sustained political commitment, community involvement, and continued collaboration among various stakeholders. In this article, we outline the current progress and challenges in curbing the HIV epidemic in the Philippines.

1. Introduction

In the past decade, the Philippines has gained notoriety as the country with the fastest-growing human immunodeficiency virus (HIV) epidemic in the Western Pacific region [ 1 ]. The first recorded cases of HIV in the Philippines were in 1985 among two then-labeled “ hospitality women ” from the cities of Angeles and Olongapo in Central Luzon [ 2 ]. Prior to 2010, the HIV epidemic was described to be “low and slow”, with about four newly diagnosed cases reported every month and a national prevalence of less than 0.1% [ 3 ]. Several factors implicated for the initial indolent rise in cases include the archipelagic geography of the Philippines, high rates of male circumcision, lower proportion of people who injecting drugs, and the culture of sexual conservatism [ 3 ].

While the overall trend of HIV incidence and AIDS-related deaths are declining globally [ 4 ], an increase in new cases was reported to the HIV/AIDS and ART Registry of the Philippines (HARP) in the recent decade ( Figure 1 ). In 2012, there were only approximately nine new HIV cases every day. In 2023, however, there have been 46 cases reported daily [ 5 ], a stunning 411% increase in daily incidence in 10 years. Late presentation in care remains a concern, with 29% of new confirmed HIV cases in January 2023 having clinical manifestations of advanced HIV disease at the time of diagnosis [ 5 ].

Estimated annual new HIV infections among individuals 15 years old and above from 2000–2021 globally and in the Philippines, based on UNAIDS estimates.

As of January 2023, there were 110,736 HIV cases reported in the Philippines [ 5 ]. Although this number seems low considering that the country has over 109 million people [ 6 ], the pervasive stigma, sociopolitical conditions, and barriers to healthcare services are fueling the epidemic in marginalized populations. The number of people living with HIV (PLHIV) is projected to increase by 200% from 158,400 in 2022 to 364,000 by 2030 [ 7 ]. Despite these challenges, there were advances in the rollout of newer antiretroviral agents, access to pre-exposure prophylaxis, and healthcare legislations that positively impact HIV treatment and prevention. In this narrative review, we outline the current progress and challenges in curbing the HIV epidemic in the Philippines.

2. Populations Disproportionately Impacted by HIV

Populations disproportionately affected by HIV include key populations, comprising 92% of the new infections in 2022, and vulnerable populations [ 7 ]. Key populations include males having sex with males (MSM), transgender women, sex workers, trafficked women and girls, and people who inject drugs (PWID) [ 7 ]. Vulnerable populations include migrant workers, people with disabilities, people in enclosed spaces, and female partners of key populations [ 7 ].

2.1. Men Having Sex with Men

Sexual transmission remains to be the predominant mode of HIV acquisition in the Philippines, primarily among MSM [ 5 ]. One of the earliest HIV prevalence studies among MSM was conducted in 2010. HIV testing performed outside the entertainment areas/gay bars of Manila found that, among 406 MSM screened using rapid HIV antibody test kits, 48 tested positive (11.8% [95% confidence interval: 8.7% to 15.0%]). Forty participants consented to a Western blot confirmatory test, with 39 participants testing positive for HIV-1 and one patient testing positive for both HIV-1 and HIV-2 [ 8 ]. Data from the Philippine Department of Health (DOH) in January 2023 showed that approximately 70% of all HIV cases were among males who have sex with other males, and 17% were among males who have sex with both males and females [ 5 ].

2.2. Persons Who Inject Drugs

HIV transmission through the sharing of infected needles remains relatively low in the Philippines. It was reported to be highest in 2010, accounting for 9% of all new HIV cases that year [ 9 ]. In the same year, an outbreak of HIV and hepatitis C virus (HCV) occurred in Cebu City, where over 50% of PWID were found to have HIV, and 93% were infected with HCV [ 10 ]. HIV transmission through infected needles has decreased since 2011 and constitutes ~1% of all newly reported cases in the past few years [ 9 ]. However, due to the recent sociopolitical climate, particularly during former president Rodrigo Duterte’s “ war on drugs” [ 11 ], it is likely that data among PWID and among those who use illicit drugs remain underreported for fear of legal ramifications. The last biobehavioral surveillance data among PWID were reported in 2015.

Needle and syringe programs (NSPs) provide access to sterile needles and syringes and facilitate their safe disposal. NSPs have been shown to effectively reduce HIV transmission [ 12 ]. However, the implementation of NSPs remain difficult in the Philippines given that the Comprehensive Dangerous Drugs Act of 2002 (Republic Act [RA] 9165) considers any unauthorized possession of drug paraphernalia as prima facie evidence of self-administration of dangerous drugs [ 13 ]. Violation could lead to a maximum of 4 years imprisonment and a minimum monetary penalty of PHP 10,000 (~USD 182) [ 13 ], which is higher than the upper bound of the average monthly minimum wage in 2022 [ 14 ]. Political pressure and the Dangerous Drugs Act of 2022 continue to make NSPs inaccessible, deterring effective community-based comprehensive HIV prevention services among PWID. The Big Cities Project (BCP) in Cebu funded by the World Bank and the Asian Development Bank aimed to reduce HIV transmission by reducing risk behaviors among PWID. However, the sterile needle distribution aspect of this project was halted within 5 months of implementation due to political pressure [ 15 , 16 ]. Mental health and substance use disorders need to be addressed as part of a comprehensive response to the HIV epidemic in the Philippines.

2.3. Transgender Populations

In the HIV surveillance systems of the Philippines, transgender women were previously included under MSM until 2018 when the HARP and the Integrated HIV Behavioral and Serologic Surveillance (IHBSS) disaggregated data based on gender identity. Of the total reported new HIV cases in January 2023, 3% were transgender women [ 5 ]. Unique concerns among transgender populations in the Philippines include differences in HIV knowledge, need for safe sex communication, and disparate access to healthcare services [ 17 ]. One study among trans men and trans women ( N = 525) in Metro Manila showed that as many as 82% declined HIV testing and counseling services [ 18 ]. Amid the gaps in healthcare access, a community-led health service delivery model providing integrated HIV and gender-affirming care showed promise in providing essential health services to transgender people [ 19 ].

2.4. Other Vulnerable Groups

There are other populations in the Philippines vulnerable to HIV. These include migrant workers, people who exchange sex, people trafficked for sex, and people in enclosed spaces.

Despite efforts to abolish policies that discriminate against PLHIV, several countries continue to mandate HIV antibody testing prior to migration or employment [ 20 ]. Historically, overseas Filipino workers (OFWs) have comprised a significant proportion of HIV cases, likely because of increased case detection from the pre-departure HIV testing imposed by their prospective employers abroad. In a 2006 publication, it was reported that, of 2410 HIV seropositive cases in the Philippines, 821 (34%) were OFWs [ 21 ]. As HIV testing entry requirements are eased by countries globally and the epidemic affects other key populations, there has been a decline in the proportion of OFWs diagnosed to have HIV. In January 2023, OFWs comprised only 5% ( N = 76) of newly diagnosed cases in the Philippines [ 5 ]. In a serological study of over 69,000 OFWs screened for HIV antibody, only one (0.001%) tested positive [ 22 ]. OFWs remain vulnerable to HIV due to the intersectionality of sociocultural factors, stigma, working conditions abroad, and barriers to healthcare access [ 23 ].

Data from the Young Adult Fertility and Sexual Health (YAFSH) study showed that 1% of Filipino men and 0.03% of women aged 15 to 24 years paid for sex in 2021, while 1% of men and 0.1% of women received payment for sex [ 24 ]. High-risk behaviors were also reported in this survey, with only 13% of male youth using condoms every time they paid for sex in the past 12 months [ 24 ]. Vulnerable populations are more likely to engage in transactional sex. For instance, female sex workers previously constituted majority of the HIV cases during the early part of the epidemic [ 25 ]. Moreover, around 38% of MSM and transgender women surveyed in the IHBSS 2018 reported receiving payment in exchange for sex in the past year [ 26 ]. Additionally, sex work has been reported outside of urban areas, as demonstrated by the “ call boys ” in rural fish ports [ 27 ]. Although commercial sex work is illegal in the Philippines, transactional sex encompasses “nonmarital, noncommercial sexual relationships motivated by the implicit assumption that sex will be exchanged for material benefit or status” [ 28 ]. Alcohol, drugs, monetary gifts, and housing have also been implicated as drivers of transactional sex [ 29 ]. Young people who engage in transactional sex have increased risk of alcohol and substance use, as well as of HIV and sexually transmitted infections [ 28 , 29 ].

According to human rights groups, the Philippines is a major sex trafficking hub in Southeast Asia. Underage Filipinos as young as 14 years old have been reported to trade sex while working in entertainment bars, spas, or illegal brothels [ 30 ]. The minors, compared to the older workers, were more likely to have been told to have sex without a condom by their managers [ 30 ]. Some risk factors for sex trafficking that have been identified include a history of childhood abuse, gender inequality, and poverty [ 31 ].

Multiple social vulnerabilities prior to incarceration, the prison environment, and management practices in these facilities have magnified HIV vulnerability among prisoners in the Philippines [ 32 ]. This is a particularly urgent issue as the recent “war on drugs” was associated with the 511% congestion rate in prisons and jails in the Philippines, fueling the twin epidemic of HIV and HCV [ 33 , 34 ].

3. The “ABCs” of HIV Prevention

HIV prevention efforts have traditionally focused on the ABCs: abstinence, being faithful, and condom use [ 35 ]. Among MSM, several reasons for not using condoms were trust in one’s sexual partner, diminished pleasure, and unavailability of condoms [ 8 ]. Among heterosexuals, condoms were perceived primarily as a birth control measure rather than as protection against HIV and sexually transmitted infections [ 36 ]. Other barriers identified were the stigma associated with purchasing a condom, as it is associated with premarital sex or infidelity [ 36 ]. Behavioral and cultural challenges to these interventions call for more robust prevention strategies, including pharmacological interventions (pre-exposure prophylaxis, PrEP), increased HIV testing, and treatment as prevention. The seventh AIDS Medium Term Plan (2023–2028), serving as the country’s blueprint to address the HIV epidemic, aims to expand access to combination prevention services and to address social, gender inequities, and stigma [ 7 ].

Stigma is an attribute causing people to be perceived as less or shamed, and it can be (1) enacted through experiencing discrimination, (2) felt through vulnerability toward discrimination, or (3) internalized through self-validation of negative societal experiences [ 37 ]. Stigma is enacted through various forms of discrimination, including victimization, violence, and macro- and microaggressions, by different perpetrators, including by the general public, employers, healthcare workers, or even oneself, friends, and family [ 38 , 39 ]. Stigma and discrimination are associated with poor quality of life and poor physical and mental health outcomes [ 40 , 41 , 42 , 43 ], which affect engagement in HIV-related services [ 44 , 45 ]. In the Philippine PLHIV Stigma Index 2019, about one in five reported stigma and discrimination within the past year, mostly from being gossiped by friends and/or family [ 46 ]. There were reports of HIV status disclosure without consent, particularly among coworkers [ 46 ]. Around one in three reported that their HIV status negatively affected their self-efficacy, most commonly in losing desire to have children [ 46 ]. There were also reports of feelings of worthlessness, shame, guilt, and self-exclusion [ 46 ].

Populations disproportionately affected by HIV experience multiple sources of stigma, from their serostatus, race and/or ethnicity, sex assigned at birth, sexual orientation, gender identity and/or expression (SOGIE), drug-injecting behavior, sex work, religious beliefs, language, culture, and social class [ 37 , 39 , 47 ]. MSM living with HIV in Manila described perceptions of being immoral and fatalistic, which often perpetuate internalized shame and hopelessness [ 37 ].

Stigma may be present even within groups of sexual and gender minorities; in particular, transgender women in the Philippines report discomfort in accessing HIV services in facilities focused on MSM [ 48 ]. People who use drugs are often targets of stigma perpetuated by the current sociopolitical climate [ 42 ]. The burden of multiple sources of stigma and their deep underpinning in larger social, political, and cultural contexts of inequity and power warrant a lens of intersectionality on studying health disparities based on stigma [ 49 ]. Being mindful of the intersecting social determinants of health is crucial in tackling health issues, particularly among populations with overlapping behaviors that put them at higher risk of HIV, such as key populations engaging in sexualized drug use (e.g., “chemsex” among MSM) and key populations engaging in sex work or transactional sex.

5. HIV Counseling and Testing

The World Health Organization (WHO) recommends that, in countries with less than 5% HIV prevalence, HIV testing should be offered to (a) individuals who present in clinical settings with manifestations and conditions suggestive of HIV primary or coinfection, such as tuberculosis and sexually transmitted infections, (b) children and infants who are symptomatic or exposed to HIV, (c) key populations and their partners, and (d) all pregnant individuals [ 50 ]. In the Philippines, HIV testing remains focused among the aforementioned key populations. Barriers to HIV testing among Filipinos included HIV-related stigma, misconceptions about the virus, fear of testing HIV-positive, and financial instability [ 51 ]. Particularly among MSM, barriers to HIV screening included perception of not needing the test due to the absence of symptoms, feeling morally superior, belonging to a higher socioeconomic class, inaccessibility of the testing facility, uncertainty of treatment side-effects, and fear of HIV-related healthcare expenses [ 52 ].

Historically, the Philippine AIDS Prevention and Control Act of 1998 (RA 8504) required pre-test and post-test counseling by a certified HIV counselor, amid their limited number, and required parental consent for HIV testing among individuals less than 18 years old, despite their level of risk for HIV [ 53 ]. In 2018, RA 8504 was revised into the Philippine HIV and AIDS Policy Act of 2018 (RA 11166). This law expanded HIV testing to include provider-initiated counseling and testing, allowing licensed social workers and health service providers to provide HIV testing services [ 54 ]. Furthermore, RA 11166 allows HIV testing among individuals 15–17 years old without parental consent [ 54 ].

Community-based organizations (CBOs) have played a key role in improving access to HIV prevention services in the Philippines. CBOs were at the forefront of research, advocacy, and policy work that expanded HIV testing from the traditional facility-based screening to now include community-based screening and HIV self-testing [ 55 , 56 ]. Monumental to the introduction of HIV self-testing in the country were HIV self-testing demonstration projects held in the Western Visayas region and in Metro Manila [ 57 , 58 ]. In the former, multiple CBO project sites reached many first-time testers among MSM and trans women [ 57 ]. In the latter, participants reported high acceptability for HIV self-testing [ 58 ]. In both projects, about 8–9% tested positive for HIV antibody, and more than half were linked to further testing and treatment [ 57 , 58 ]. These projects were conducted successfully despite the stringent quarantine protocols during the COVID-19 pandemic. It was estimated that there was a 61% decrease in the number of HIV tests performed and a 37% decrease in HIV diagnosis in 2020 nationally, attributed largely to the quarantine restrictions imposed during the COVID-19 pandemic [ 59 ], further highlighting the importance of improving the accessibility of HIV testing services in the community.

Given the success of community-led HIV testing projects, HIV self-testing was included in the national HIV testing guidelines in 2022 [ 56 ]. However, challenges remain in the rollout of HIV self-testing. Most of the HIV self-testing kits in the Philippines are blood-based tests, despite the acceptability of oral-based tests [ 60 ]. Moreover, there are unauthorized online sellers of HIV test kits [ 61 ]. Regulations must be strengthened to ensure the quality of HIV test kits purchased online. Furthermore, support systems must be in place to facilitate linkage to care, making medical and psychosocial support accessible for persons who test positive at home.

In addition to HIV self-testing, social network and index testing (partner notification) were recently included as HIV testing approaches [ 56 ]. While benefits outweigh the risk, index testing is associated with experiences of intimate partner violence [ 62 , 63 ]. In the Philippines, where intimate partner violence among cisgender women is prevalent [ 64 ] and national legislative protections for sexual and gender minorities are lacking [ 65 ], it is imperative for the country to improve violence prevention and push forward legislations that will protect the rights and wellbeing of key and vulnerable populations regardless of HIV status.

In 2019, the Philippines started to transition from the use of the Western blot test for HIV confirmation to the rapid HIV diagnostic algorithm (rHIVda), which involves the use of three rapid diagnostic test kits to confirm HIV diagnosis ( Figure 2 ) [ 66 , 67 ]. This approach decentralized confirmation of HIV diagnosis from a couple of reference laboratories in Metro Manila to the 38 certified rHIVda confirmatory laboratories around the country as of September 2022 [ 68 ]. RHIVda significantly decreased waiting time for HIV confirmation and facilitated linkage to care from weeks to days [ 68 ]. As there are limited algorithms approved in the Philippines [ 69 ], stock issues in rapid diagnostic test kits present a potential challenge. Nonetheless, the continuous validation of kits and consideration of new technologies provide flexibility to this challenge [ 67 , 69 ].

Traditional versus rapid HIV diagnostic algorithm in the Philippines. Abbreviations: rHIVda: rapid HIV diagnostic algorithm; IA: immunoassay.

6. HIV Pre-Exposure Prophylaxis (PrEP)

PrEP is the use of combination antiretrovirals for HIV prevention indicated for people who are HIV-seronegative at substantial risk for HIV [ 50 , 70 ]. Depending on a person’s risk behavior, PrEP may be taken daily or “on demand”/event-driven. Event-driven PrEP, otherwise known as “2–1–1”, is currently recommended by the WHO to prevent sexual acquisition of HIV by cisgender men and trans and gender diverse people assigned male at birth who are not taking hormones that are estradiol-based [ 70 ]. In this regimen, a person takes two pills of emtricitabine/tenofovir 2–24 hours before potential exposure, one pill 24 hours after the first dose, and one pill 24 hours after the second dose [ 70 , 71 ].

A landmark pilot implementation project that paved the way to the approval of PrEP in the Philippines was the community-led program called Project PrEPPY. In this 2 year pilot implementation, there were no reported new HIV infections, no increase in condomless anal intercourse, and no significant increase in STI incidence from baseline among MSM and transgender women who used PrEP [ 72 ].

Emtricitabine–tenofovir disoproxil fumarate (TDF) was the first approved PrEP medication [ 73 ]. Chronic use of TDF has been associated with mild kidney-related adverse events [ 74 ] and decreased bone mineral density [ 75 ]. A newer prodrug of tenofovir (tenofovir alafenamide) was shown to have less impact on the kidney and bone mineral density [ 76 ], but was associated in some studies with weight gain and lipid disorders [ 77 , 78 ].

In 2021, the WHO recommended dapivirine vaginal rings (DPV-VR) as a new choice for HIV prevention for women at substantial risk of HIV infection [ 79 ]. DPV-VR is a bendable silicone ring inserted into the vagina that slowly releases the antiretroviral dapivirine, replaced every 28 days [ 79 ]. In 2022, long-acting cabotegravir, which is administered intramuscularly 4 weeks apart for the first two injections and then every 8 weeks thereafter, was recommended by the WHO as an additional prevention choice for people at substantial risk of HIV infection [ 80 ]. However, only oral emtricitabine–TDF is currently available in the Philippines and is not covered by the national health insurance. Donor-funded emtricitabine–TDF is limited, and the out-of-pocket cost is about USD 30–65 for a 30-tablet bottle. It must be noted that the minimum wage in the National Capital Region is about PHP 500 (~USD 9.20) per day (minimum wage is lower in other regions of the Philippines) [ 14 ], limiting the accessibility of PrEP, especially among people living in poverty.

7. HIV Post-Exposure Prophylaxis (PEP)

Persons without HIV who may have been recently exposed to HIV may take post-exposure prophylaxis (PEP) as soon as possible within 72 hours of high-risk exposure to prevent HIV acquisition [ 81 ]. PEP implementation in the Philippines remains limited to healthcare-related exposure, in both clinical and community-based settings [ 55 , 82 ]. The Philippine Health Sector HIV Strategic Plan 2020–2022 aimed to expand PEP to non-healthcare-related exposures [ 83 ].

8. HIV Treatment and Care Delivery

8.1. access to hiv services.

As of January 2023, there were about 180 treatment hubs and primary HIV care facilities in the Philippines [ 5 ]. ART is dispensed only through these designated facilities and is not available from commercial pharmacies, which may pose as a challenge for PLHIV living in rural areas trying to access ART [ 1 , 84 ]. While the national HIV program provides ART for free to PLHIV, other fees for medical care, such as consultation fees and laboratory tests, may be covered by the national health insurance, Philippine Health Insurance Corporation (PhilHealth), through their Outpatient HIV/AIDS Treatment (OHAT) Package. The OHAT package provides an annual reimbursement of PHP 30,000 (~USD 544), which is paid to the treatment facility where the PLHIV is enrolled [ 85 ]. In 2022, it was estimated that one in three PLHIV was not enrolled in OHAT [ 7 ].

The OHAT package provides financial support to PLHIV and covers the biomedical aspect of the HIV care cascade. However, other components essential to strengthen HIV management, such as peer support and counseling, psychosocial support, and ancillary services for shelter and violence response/prevention are mostly out of pocket, if not covered by external funding, particularly from donor organizations, or by the national program through domestic funding.

Although domestic funding comprises 94% of HIV spending from government sources, through the national HIV program and PhilHealth, with 6% coming from external sources, these only constitute 40% of the financial requirement to reach the 95–95–95 UNAIDS target (see Section 9 ), leaving a 60% funding gap [ 7 ]. The country’s transition toward universal healthcare (UHC), since the passage of the UHC Law (RA 11223) [ 86 ], goes hand in hand with RA 11166 in providing sustainable mechanisms to address these financial gaps. Moreover, the Mandanas Ruling by the Supreme Court would potentially increase the share of local government units from national taxes, which could also contribute to address these gaps if HIV and healthcare services are prioritized at the local level [ 7 ].

8.2. Antiretroviral Therapy (ART)

Although studies to cure HIV through various novel techniques are ongoing, such as bone marrow transplant and gene therapy [ 87 , 88 ], there remains no commercially available cure for PLHIV. Plasma HIV RNA suppression is achieved through regular ART. Early in the infection, HIV establishes latency in various cellular and tissue reservoir sites, including the central nervous system, gut lymphoid tissue, and resting memory CD4 T cells [ 89 ]. ART controls active viral replication in the plasma but does not completely eradicate viruses in these reservoir sites. Once ART is stopped, viral load rebounds [ 90 ].

For several years, the only available one pill once a day ART regimen in the Philippines has been lamivudine/TDF/efavirenz (LTE). Although efavirenz is a potent non-nucleoside reverse transcriptase inhibitor, it is known to cause neuropsychiatric symptoms, such as vivid dreams, severe depression, or suicidal ideation, which have been reported in up to 50% of patients [ 91 ]. In July 2019, the WHO issued a statement that the integrase strand transfer inhibitor (INSTI) dolutegravir is the preferred first-line and second-line treatment option for all populations [ 92 ]. This was based on multiple studies showing that dolutegravir is more effective in achieving virological suppression, is better tolerated, and is more cost-effective than alternative drugs [ 92 ]. Furthermore, dolutegravir displays potent in vitro activity and a lower barrier for genetic resistance development [ 93 ].

In 2020, the Philippines started prescribing TDF/lamivudine/dolutegravir (TLD) single-formulation tablets. The Philippine government prioritized the use of TLD among newly diagnosed PLHIV and among patients with severe side-effects from the current efavirenz-based regimen [ 94 ]. Significant progress has transpired with the inclusion of TLD in the Philippine National Formulary in 2021 [ 95 ], enabling government procurement. The Philippine HIV treatment guidelines were also revised in 2022 [ 96 ], officially recommending dolutegravir-based ART as the first-line regimen for PLHIV.

The long-acting injectable combination of cabotegravir/rilpivirine has been approved by the US FDA for use in adult PLHIV who are virologically suppressed on a stable ART regimen [ 97 ]. Cabotegravir/rilpivirine is administered by a healthcare provider as an intramuscular (gluteal) injection every 2 months [ 98 ] and replaces the need for daily oral ART. This medication is currently not available in the Philippines.

8.3. Tuberculosis and Hepatitis B Co-Infection

The treatment of PLHIV with tuberculosis (TB) co-infection remains a challenge in a country with one of the highest TB/HIV burdens in Asia [ 99 ]. Rifampicin, one of the key medications for long-term tuberculosis treatment, reduces dolutegravir exposure, requiring an additional dose of dolutegravir to be administered 12 hours after the standard daily dose [ 100 ]. However, the single-formulation dolutegravir 50 mg tablet remains difficult to access in the Philippines. This limits the use of TLD, particularly among the estimated 12,000 individuals with TB/HIV co-infection [ 101 ]. Moreover, PLHIV who have treatment failure with efavirenz are further disadvantaged, as they are likely taking protease inhibitors which have serious drug–drug interactions with rifampicin [ 102 ].

Another challenge in the ART management among PLHIV in the Philippines is the high burden of hepatitis B virus (HBV) in the country, with an estimated Hepatitis B surface antigen (HBsAg) seroprevalence of 16.7% in the general population [ 103 ]. Prevalence data on HBV/HIV co-infection in the Philippines remain limited, but one study reported that, among PLHIV ( N = 302), 13.3% ( n = 40) were co-infected with HBV [ 104 ]. The use of certain ART in the setting of HIV/HBV co-infection (such as TDF and lamivudine) requires careful monitoring, since chronic HBV may increase the risk of hepatotoxicity from ART and abrupt discontinuation of ART with anti-HBV activity may lead to HBV reactivation and fulminant hepatitis [ 105 , 106 ].

8.4. Treatment as Prevention

VL suppression is not only essential in decreasing morbidity and mortality among PLHIV, but also a key measure to prevent HIV transmission in the community. In recent years, the public health message “ undetectable = untransmittable (U=U)” has gained significant traction to fight stigma and promote ART adherence. PLHIV who achieve and maintain an undetectable viral load by regularly taking ART as prescribed will not sexually transmit HIV to others [ 107 ]. This concept of U=U is underpinned by “treatment as prevention”, where achieving viral load suppression through ART is used as a prevention strategy at the population level [ 108 ]. Communicating U=U was associated with improved overall sexual and mental health, medication adherence, and viral load suppression [ 109 ]. Moreover, it is a huge step in de-stigmatization, particularly among people who face multiple intersecting stigma [ 108 , 110 ].

8.5. Maternal–Child Transmission

A total of 724 women in the Philippines were diagnosed to have HIV during their pregnancy between January 2011 to January 2023 [ 5 ]. The DOH started to recommend triple screening among pregnant women for HIV, syphilis, and HBV in 2016 [ 111 ]. This is aligned with the global movement for the triple elimination of HIV, syphilis, and HBV. Only 15% of pregnant women are receiving ART for the prevention of mother-to-child transmission (MTCT) [ 112 ]. Although newer recommendations on antiretroviral prophylaxis among HIV-exposed infants were provided in the recently revised HIV treatment guidelines [ 96 ], the last DOH guidelines on prevention of MTCT was published in 2009 [ 113 ]. Updating these guidelines is crucial to ensure continuity of standard of care across all the components of the MTCT cascade.

9. Viral Load Monitoring, Genotyping, and Resistance Testing

The Joint United Nations Program on HIV/AIDS (UNAIDS) set a global target of 95–95–95 by 2030: 95% know their HIV status, 95% are on ART, and 95% have achieved viral load suppression [ 114 ]. As of September 2022, the Philippines has achieved 63–65–97 [ 7 ]. It should be noted, however, that the 97% viral suppression rate was based only among 20% of PLHIV on ART who were tested for plasma HIV RNA [ 7 ]. A study on the care cascade of 3137 MSM diagnosed to have HIV in a community-based clinic in Manila showed a 98% viral suppression rate among 84% of PLHIV on ART who were tested for viral load [ 115 ]. In another surveillance study, an HIV clinic in a tertiary hospital found 95% viral suppression among the 48.2% of PLHIV on ART who had viral load testing [ 116 ].

HIV RNA viral load testing is unfortunately not routinely performed in the country due to the associated costs and limited availability [ 116 ]. An administrative order was issued by the DOH in 2022 to facilitate the integration of HIV and TB services. This collaborative approach to the prevention and control of TB and HIV aims to increase the access to polymerase chain reaction (PCR) machines for HIV viral load and TB diagnosis [ 117 ].

Where resources are available, baseline HIV drug resistance testing is recommended to guide the selection of the initial ART regimen [ 118 ]. HIV genotype testing is also helpful to facilitate the switching of medications in the event of treatment failure. However, low- and middle-income countries face challenges in accessing HIV drug resistance testing. In 2013, deep sequencing analysis to assess drug-resistance mutations (DRMs) among PLHIV in the Philippines showed that only two from the 110 evaluable individuals with major HIV variants were highly resistant to non-nucleoside reverse transcriptase inhibitors (NNRTI: efavirenz and nevirapine). However, minority drug-resistant HIV variants were detected: highly resistant to nevirapine (89/110), rilpivirine (5/110), and efavirenz (49/110) [ 119 ]. A study published in 2017 among a relatively small sample of treatment-naïve PLHIV in the Philippines ( N = 95) showed transmitted drug resistance (TDR) in six patients (6.3%) [ 120 ]. In a more recent publication of PLHIV ( N = 513) on ART, 10.3% experienced treatment failure after 1 year [ 121 ]. Among those who failed treatment ( n = 53), 90.6% had DRMs. The study found unexpectedly high rates of NRTI, NNRTI, and K65R tenofovir resistance, as well as multiclass resistance [ 121 ]. These data emphasize the need for continued efforts to increase viral load and drug resistance testing in the Philippines.

10. Changing Molecular Epidemiology of HIV

The increase in HIV cases in the Philippines is multifactorial and cannot only be attributed to various healthcare, socioeconomic, and political factors. The changing molecular epidemiology of the virus may also be fueling transmission. During the early part of the epidemic, subtype B was the prevailing HIV-1 subtype in the country. However, multiple studies in the past decade have shown that CRF_01AE is now the predominant subtype, constituting over 70% of strains among newly diagnosed PLHIV [ 122 , 123 ]. CRF_01AE appears to be a more aggressive subtype, reported in various cohorts to cause more rapid CD4 T-cell decline and faster HIV/AIDS progression [ 121 , 124 , 125 ]. The poorer outcomes associated with this predominant HIV subtype circulating in the Philippines should be an impetus for various stakeholders to further ramp up HIV testing, treatment, and care delivery in the country.

11. Conclusions

There has been significant progress in HIV treatment and prevention in the Philippines. The Philippine HIV and AIDS Policy Act of 2018 expanded access to HIV services in the country [ 54 ]. HIV testing now includes community-based screening and self-testing [ 56 ] and allows for the screening of minors 15–17 years old without parental consent [ 54 ]. Newer antiretrovirals have been procured, and dolutegravir-based ART is now first line, consistent with the WHO recommendations [ 92 ]. PrEP has been rolled out [ 72 ]. The number of treatment hubs and primary HIV care facilities continues to increase. However, barriers including stigma, limited harm reduction services for PWID, and sociocultural and political deterrents remain. HIV RNA viral load testing and drug resistance testing are not routinely performed due to associated costs and limited resources. The high burden of TB and HBV co-infection complicates HIV management [ 102 , 104 ]. PrEP and PEP need to be expanded to further reach populations at risk. The HIV epidemic in the Philippines requires a multisectoral approach and calls for sustained political commitment, community involvement, and continued collaboration among various stakeholders.

Funding Statement

This review article received no external funding.

Author Contributions

L.M.A.G. and P.C.E. contributed equally to this article. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

The authors declare no conflict of interest. The views and opinions expressed in this article do not reflect the views and opinions of the authors’ affiliations.

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Volume 630 Issue 8015, 6 June 2024

Online misinformation is frequently highlighted as a blight that threatens to undermine the fabric of society, polarize opinions and even destabilize elections. In this week’s issue, a collection of articles probe the scourge of misinformation and try to assess the real risks. In one research paper , David Lazer and colleagues examine the effects of Twitter deplatforming 70,000 traffickers of misinformation in the wake of violent scenes at the US Capitol in January 2021. In a second paper , Wajeeha Ahmad and co-workers explore the relationship between advertising revenue and misinformation. A Comment article by Ullrich Ecker and colleagues discusses the risks posed by misinformation to democracy and elections, and an accompanying Comment article by Kiran Garimella and Simon Chauchard assesses the prevalence of AI-generated misinformation in India. Finally, David Rothschild and colleagues put the harms of misinformation into perspective , highlighting common misperceptions that exaggerate its threat and suggesting steps to improve evaluation of both the effects of misinformation and the efforts made to combat it.

Cover image: Kelly Krause/Nature

What we do — and don’t — know about how misinformation spreads online

There are gaps in our understanding of how and why digital misinformation propagates. To help design effective interventions to minimize the spread of falsehoods, researchers need data and transparency from online platforms.

Advertisement

Meta’s AI system is a boost to endangered languages — as long as humans aren’t forgotten

Automated approaches to translation could provide a lifeline to under-resourced languages, but only if companies engage with the people who speak them.

Negotiating a pandemic treaty is just the first step — how will countries comply?

Governments must act now on vaccine and pathogen-sample sharing, or any agreement will be a promise only on paper.

• Tae Jung Park

Research Highlights

Ancient dna reveals extinct flightless bird’s superpowers.

The little bush moa had small eyes, no wings and some extraordinary skills.

Karaoke-related stress soars after a good night of REM sleep

The emotional load of listening to one’s own performance is preserved by a certain type of sleep.

More than a billion people live in ‘energy poverty’

Satellite data help to show that many people with access to electricity cannot take advantage of it.

Sex hormones in the gut soar during pregnancy — thanks to busy bacteria

Two species in the gut microbiome transform corticosteroids into progestins, which can affect mood and behaviour.

News in Focus

The immune system can sabotage gene therapies — can scientists rein it in.

People treated with gene therapy cannot receive a second dose for fear of a dangerous immune response. Researchers hope to find a way around this.

• Heidi Ledford

Who will make AlphaFold3 open source? Scientists race to crack AI model

Researchers are aiming to create fully accessible versions of the latest iteration of DeepMind’s blockbuster protein-structure model.

• Ewen Callaway

Ozempic keeps wowing: trial data show benefits for kidney disease

Semaglutide, the same compound in obesity drug Wegovy, slashes risk of kidney failure and death for people with diabetes.

• Rachel Fairbank

Bizarre bacteria defy textbooks by writing new genes

Bacterial defensive systems scramble the standard workflow of life.

First pig-to-human liver transplant recipient ‘doing very well’

The transplant aims to prolong the the person’s life and provides important lessons for physicians.

• Smriti Mallapaty

Collection:

• Cancer at Nature Portfolio

The cicadas are here! Why US researchers are swarming to study them

Two particular broods of the insects are popping up together for the first time in two centuries, and there’s a lot we don’t know about them.

• Sumeet Kulkarni

Element from the periodic table’s far reaches coaxed into elusive compound

Chemists achieve synthetic feat with radioactive promethium for the first time.

• Mark Peplow

The AI revolution is coming to robots: how will it change them?

The melding of artificial intelligence and robotics could catapult both fields to new heights.

• Elizabeth Gibney

Exclusive: How NASA astronauts are training to walk on the Moon in 2026

Simulated lunar exploration in an Arizona volcanic field this month helped astronauts to prepare for doing geology in harsh conditions at the lunar south pole. Nature joined mission control.

• Alexandra Witze

Misinformation poses a bigger threat to democracy than you might think

In today’s polarized political climate, researchers who combat mistruths have come under attack and been labelled as unelected arbiters of truth. But the fight against misinformation is valid, warranted and urgently required.

• Ullrich Ecker
• Jon Roozenbeek
• Stephan Lewandowsky

How prevalent is AI misinformation? What our studies in India show so far

A sample of roughly two million WhatsApp messages highlights urgent concerns about the spread and prevalence of AI-generated political content.

• Kiran Garimella
• Simon Chauchard

Correspondence

Mega engineering projects won’t stop a repeat of the devastating southern brazil floods.

• Luiz Roberto Malabarba
• Fernando Gertum Becker
• Márcio Borges-Martins

Neurotechnologies that can read our mind could undermine international norms on freedom of thought

• Christoph Bublitz

Organic product legislation ignores agricultural plastic use — that must change

• Andrea M. Alma
• Micaela Buteler

Underfunding cannabis research hampers sensible policymaking and boosts the black market

• Davoud Torkamaneh

What steps to take when funding starts to run out

Although researchers often face uncertainty when grants expire with no replacement in sight, there are creative ways to ease the dry spell.

• Neil Savage

Career Guide:

• Funding science

Technology Feature

How to keep the lights on: the mission to make more photostable fluorophores.

Fluorescent labels that have greater resistance to bleaching could help researchers to get more from biological imaging.

• Ariana Remmel

Where I Work

I breed and release arctic foxes to boost their numbers in the wild.

Over the past 25 years, Kristine Ulvund has helped to increase the species’ population size from 50 or so individuals to more than 500.

• Rachel Nuwer

News & Views

Brain fluid probed by ultrasound using squishy cubes.

Soft solids that swell with shifts in pressure, temperature and pH provide a way of detecting such changes in the fluid around the brain. The method could be used to determine other properties of fluids elsewhere in the body.

• Jules J. Magda

Neural pathways for reward and relief promote fentanyl addiction

Neuroscientists find that two distinct neural pathways are responsible for the addictive properties of the opioid fentanyl: one mediates reward, the other promotes the seeking of relief from symptoms of withdrawal.

• Markus Heilig
• Michele Petrella

Designer porous solids open up vast sandbox for materials research

A simple design approach and predictive computational methods have spawned a pathway for making materials that could trap specific molecules — an ability needed for applications such as carbon capture.

• Dejan-Krešimir Bučar

Cells cope with altered chromosome numbers by enhancing protein breakdown

When chromosomes are lost or gained, massive changes in gene expression disrupt the delicate balance of proteins in a cell. Yeasts with incorrect chromosome numbers counteract this by degrading excess proteins.

• Zuzana Storchová

Microbes ‘sieve’ ions on their surface to start the nitrogen cycle

Uptake of ammonium ions by marine microorganisms called archaea is a key first step in the conversion of ammonium to nitrogen found in ecosystems. Structural evidence reveals how archaea capture ammonium in an efficient way.

• Henry van den Bedem

Perspective

Misunderstanding the harms of online misinformation.

This Perspective identifies common misperceptions regarding the harms of online misinformation, finding that exposure to false and inflammatory content is rare and concentrated among a small minority of people who already have extreme views.

• Ceren Budak
• Brendan Nyhan
• Duncan J. Watts

Star formation shut down by multiphase gas outflow in a galaxy at a redshift of 2.45

JWST observations of a massive galaxy at a redshift of 2.45 show a powerful outflow of neutral gas, with a mass outflow rate that is sufficient to shut down star formation.

• Sirio Belli
• Minjung Park
• Rainer Weinberger

Wavefunction matching for solving quantum many-body problems

An approach called wavefunction matching transforms particle interactions so that their wavefunctions match those of easily computable interactions, to allow for calculations of quantum many-body systems that would otherwise be difficult or impossible.

• Serdar Elhatisari
• Lukas Bovermann
• Gianluca Stellin

Superconducting diode effect and interference patterns in kagome CsV 3 Sb 5

We observe the superconducting diode effect and interference patterns in CsV 3 Sb 5 , implying a time-reversal symmetry-breaking superconducting order in kagome superconductors.

• Zhiming Pan

Heterogeneous integration of spin–photon interfaces with a CMOS platform

A modular quantum system-on-chip architecture integrates thousands of individually addressable spin qubits in two-dimensional quantum microchiplet arrays into an integrated circuit designed for cryogenic control, supporting full connectivity for quantum memory arrays across spin–photon channels.

• Lorenzo De Santis
• Dirk Englund

Dispersion-assisted high-dimensional photodetector

By combining spatial and frequency dispersive thin-film interfaces with deep residual learning, a miniature photodetector allowing the acquisition of high-dimensional information on light in a single-shot fashion is described.

• Yandong Fan
• Weian Huang

Injectable ultrasonic sensor for wireless monitoring of intracranial signals

A bioresorbable, wireless hydrogel (metagel) sensor, encompassing both biodegradable and stimulus-responsive hydrogels for ultrasonic monitoring of intracranial signals, was implanted into intracranial space with a puncture needle and deformed in response to physiological environmental changes.

• Hanchuan Tang
• Yueying Yang
• Jianfeng Zang

Metals strengthen with increasing temperature at extreme strain rates

Microballistic impact testing at strain rates greater than 10 6  s −1 shows that pure metals, including copper, gold and titanium, become stronger with increasing temperature.

• Ian Dowding
• Christopher A. Schuh

Photocatalytic doping of organic semiconductors

A previously undescribed photocatalytic approach enables the effective p-type and n-type doping of organic semiconductors at room temperature using only widely available weak dopants such as oxygen and triethylamine.

• Wenlong Jin
• Chi-Yuan Yang
• Simone Fabiano

Porous isoreticular non-metal organic frameworks

The use of computational crystal-structure prediction has enabled the targeted assembly of frameworks of porous organic ammonium halide salts that have many of the qualities of metal–organic frameworks despite containing no metal.

• Megan O’Shaughnessy
• Joseph Glover
• Andrew I. Cooper

Capturing electron-driven chiral dynamics in UV-excited molecules

Time-resolved photoelectron circular dichroism with a temporal resolution of 2.9 fs is used to track the ultrafast electron dynamics following ultraviolet excitation of neutral chiral molecules, which generate chiral currents that exhibit periodic rotation direction reversal.

• Vincent Wanie
• Etienne Bloch
• Francesca Calegari

Life-cycle-coupled evolution of mitosis in close relatives of animals

We analyse cell division in ichthyosporeans and find that multinucleated life cycles favour the evolution of closed mitosis, in which the cell constructs a spindle within an intact nucleus.

• Marine Olivetta

Companies inadvertently fund online misinformation despite consumer backlash

Many companies unknowingly advertise on websites that publish misinformation despite the reputational and financial risks, and increased transparency for consumers and advertisers could counter unintended ad revenue going to misinformation websites.

• Wajeeha Ahmad
• Erik Brynjolfsson

Post-January 6th deplatforming reduced the reach of misinformation on Twitter

Difference-in-differences analysis indicates that the decision by Twitter to deplatform 70,000 users following the events at the US Capitol on 6 January 2021 had wider effects on the spread of misinformation.

• Stefan D. McCabe
• Diogo Ferrari
• Kevin M. Esterling

Distinct µ-opioid ensembles trigger positive and negative fentanyl reinforcement

Experiments using fentanyl treatment of mice show that µ-opioid receptors mediate positive reinforcement in the ventral tegmental area and negative reinforcement in central amygdala, thereby identifying the circuits that lead to opioid addiction.

• Fabrice Chaudun
• Laurena Python
• Christian Lüscher

Natural proteome diversity links aneuploidy tolerance to protein turnover

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

• Julia Muenzner
• Pauline Trébulle
• Markus Ralser

Multimodal decoding of human liver regeneration

Harnessing single-nucleus RNA sequencing and spatial profiling, this work dissects unanticipated aspects of human liver regeneration to uncover a novel migratory hepatocyte subpopulation mediating wound closure following acute liver injury.

• K. P. Matchett
• J. R. Wilson-Kanamori
• N. C. Henderson

Acquisition of epithelial plasticity in human chronic liver disease

Single-cell RNA sequencing and 3D imaging have revealed the cellular changes and structural reorganization that occur during the progression of human chronic liver disease and as the liver attempts to regenerate.

• Christopher Gribben
• Vasileios Galanakis
• Ludovic Vallier

Transcriptional control of the Cryptosporidium life cycle

The transcription factor Myb-M is the earliest determinant of male fate in the parasite Cryptosporidium parvum .

• Katelyn A. Walzer
• Jayesh Tandel
• Boris Striepen

A whole-slide foundation model for digital pathology from real-world data

Prov-GigaPath, a whole-slide pathology foundation model pretrained on a large dataset containing around 1.3 billion pathology images, attains state-of-the-art performance in cancer classification and pathomics tasks.

• Naoto Usuyama
• Hoifung Poon

Molecular basis for differential Igk versus Igh V(D)J joining mechanisms

Experiments in mouse models, and in cell lines that only allow primary Vκ-to-Jκ rearrangements, enable characterization of the mechanisms of V(D)J recombination.

• Yiwen Zhang

Targetable leukaemia dependency on noncanonical PI3Kγ signalling

Using a multimodal approach across acute leukaemias, a targetable PI3Kγ dependency in leukaemias is explored.

• Evangeline G. Raulston
• Andrew A. Lane

Covalent targeted radioligands potentiate radionuclide therapy

Radiopharmaceuticals engineered with click chemistry to selectively bind to tumour-specific proteins can be used to successfully target tumour cells, boosting the pharmacokinetics of radionuclide therapy and improving tumour regression.

• Xi-Yang Cui

An alternative cell cycle coordinates multiciliated cell differentiation

A distinct cell cycle redeploys many canonical cell cycle regulators to control the differentiation of multiciliated cells, with the transcription factor E2F7 playing a pivotal part in this modified cell cycle.

• Semil P. Choksi
• Lauren E. Byrnes
• Jeremy F. Reiter

Structures of human γδ T cell receptor–CD3 complex

The assembly of the γδ TCR depends on Vγ usage.

• Bangdong Huang

Membraneless channels sieve cations in ammonia-oxidizing marine archaea

The Nitrosopumilus maritimus surface layer (S-layer) concentrates ammonium ions on its cell-facing side, acting as a multichannel sieve on the cell membrane.

• Andriko von Kügelgen
• C. Keith Cassidy
• Tanmay A. M. Bharat

Structural pharmacology and therapeutic potential of 5-methoxytryptamines

Detailed analyses of the serotonin receptor 5-HT 1A and the psychedelic 5-methoxy- N,N -dimethyltryptamine reveal the differences in receptor structural pharmacology that mediate signalling specificity, efficacy and potency, findings that may facilitate the development of new neuropsychiatric therapeutics.

• Audrey L. Warren
• David Lankri
• Daniel Wacker

Dimerization and antidepressant recognition at noradrenaline transporter

Cryo-electron microscopy structures of the noradrenaline transporter in the apo state, bound to noradrenaline and bound to various antidepressants shed light on the substrate transport, molecular recognition and dimeric architecture of this protein.

• Yu-Ling Yin

Amendments & Corrections

Author correction: quantum control of a cat qubit with bit-flip times exceeding ten seconds, author correction: a small and vigorous black hole in the early universe.

• Roberto Maiolino
• Jan Scholtz

Author Correction: Large-scale plasma proteomics comparisons through genetics and disease associations

• Grimur Hjorleifsson Eldjarn
• Egil Ferkingstad
• Kari Stefansson

Nature Index

China's status at the summit of the Nature Index remains unrivalled as the gap between it and the United States grows.

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Scientific breakthroughs: 2024 emerging trends to watch

December 28, 2023

Across disciplines and industries, scientific discoveries happen every day, so how can you stay ahead of emerging trends in a thriving landscape? At CAS, we have a unique view of recent scientific breakthroughs, the historical discoveries they were built upon, and the expertise to navigate the opportunities ahead. In 2023, we identified the top scientific breakthroughs , and 2024 has even more to offer. New trends to watch include the accelerated expansion of green chemistry, the clinical validation of CRISPR, the rise of biomaterials, and the renewed progress in treating the undruggable, from cancer to neurodegenerative diseases. To hear what the experts from Lawrence Liverpool National Lab and Oak Ridge National Lab are saying on this topic, join us for a free webinar on January 25 from 10:00 to 11:30 a.m. EDT for a panel discussion on the trends to watch in 2024.

The ascension of AI in R&D

While the future of AI has always been forward-looking, the AI revolution in chemistry and drug discovery has yet to be fully realized. While there have been some high-profile set-backs , several breakthroughs should be watched closely as the field continues to evolve. Generative AI is making an impact in drug discovery , machine learning is being used more in environmental research , and large language models like ChatGPT are being tested in healthcare applications and clinical settings.

Many scientists are keeping an eye on AlphaFold, DeepMind’s protein structure prediction software that revolutionized how proteins are understood. DeepMind and Isomorphic Labs have recently announced how their latest model shows improved accuracy, can generate predictions for almost all molecules in the Protein Data Bank, and expand coverage to ligands, nucleic acids, and posttranslational modifications . Therapeutic antibody discovery driven by AI is also gaining popularity , and platforms such as the RubrYc Therapeutics antibody discovery engine will help advance research in this area.

Though many look at AI development with excitement, concerns over accurate and accessible training data , fairness and bias , lack of regulatory oversight , impact on academia, scholarly research and publishing , hallucinations in large language models , and even concerns over infodemic threats to public health are being discussed. However, continuous improvement is inevitable with AI, so expect to see many new developments and innovations throughout 2024.

‘Greener’ green chemistry

Green chemistry is a rapidly evolving field that is constantly seeking innovative ways to minimize the environmental impact of chemical processes. Here are several emerging trends that are seeing significant breakthroughs:

• Improving green chemistry predictions/outcomes : One of the biggest challenges in green chemistry is predicting the environmental impact of new chemicals and processes. Researchers are developing new computational tools and models that can help predict these impacts with greater accuracy. This will allow chemists to design safer and more environmentally friendly chemicals.
• Reducing plastics: More than 350 million tons of plastic waste is generated every year. Across the landscape of manufacturers, suppliers, and retailers, reducing the use of single-use plastics and microplastics is critical. New value-driven approaches by innovators like MiTerro that reuse industrial by-products and biomass waste for eco-friendly and cheaper plastic replacements will soon be industry expectations. Lowering costs and plastic footprints will be important throughout the entire supply chain.    
• Alternative battery chemistry: In the battery and energy storage space, finding alternatives to scarce " endangered elements" like lithium and cobalt will be critical. While essential components of many batteries, they are becoming scarce and expensive. New investments in lithium iron phosphate (LFP) batteries that do not use nickel and cobalt have expanded , with 45% of the EV market share being projected for LFP in 2029. Continued research is projected for more development in alternative materials like sodium, iron, and magnesium, which are more abundant, less expensive, and more sustainable.
• More sustainable catalysts : Catalysts speed up a chemical reaction or decrease the energy required without getting consumed. Noble metals are excellent catalysts; however, they are expensive and their mining causes environmental damage. Even non-noble metal catalysts can also be toxic due to contamination and challenges with their disposal. Sustainable catalysts are made of earth-abundant elements that are also non-toxic in nature. In recent years, there has been a growing focus on developing sustainable catalysts that are more environmentally friendly and less reliant on precious metals. New developments with catalysts, their roles, and environmental impact will drive meaningful progress in reducing carbon footprints.  
• Recycling lithium-ion batteries: Lithium-ion recycling has seen increased investments with more than 800 patents already published in 2023. The use of solid electrolytes or liquid nonflammable electrolytes may improve the safety and durability of LIBs and reduce their material use. Finally, a method to manufacture electrodes without solvent s could reduce the use of deprecated solvents such as N-methylpyrrolidinone, which require recycling and careful handling to prevent emissions.

Rise of biomaterials

New materials for biomedical applications could revolutionize many healthcare segments in 2024. One example is bioelectronic materials, which form interfaces between electronic devices and the human body, such as the brain-computer interface system being developed by Neuralink. This system, which uses a network of biocompatible electrodes implanted directly in the brain, was given FDA approval to begin human trials in 2023.

• Bioelectronic materials: are often hybrids or composites, incorporating nanoscale materials, highly engineered conductive polymers, and bioresorbable substances. Recently developed devices can be implanted, used temporarily, and then safely reabsorbed by the body without the need for removal. This has been demonstrated by a fully bioresorbable, combined sensor-wireless power receiver made from zinc and the biodegradable polymer, poly(lactic acid).
• Natural biomaterials: that are biocompatible and naturally derived (such as chitosan, cellulose nanomaterials, and silk) are used to make advanced multifunctional biomaterials in 2023. For example, they designed an injectable hydrogel brain implant for treating Parkinson’s disease, which is based on reversible crosslinks formed between chitosan, tannic acid, and gold nanoparticles.
• Bioinks : are used for 3D printing of organs and transplant development which could revolutionize patient care. Currently, these models are used for studying organ architecture like 3D-printed heart models for cardiac disorders and 3D-printed lung models to test the efficacy of drugs. Specialized bioinks enhance the quality, efficacy, and versatility of 3D-printed organs, structures, and outcomes. Finally, new approaches like volumetric additive manufacturing (VAM) of pristine silk- based bioinks are unlocking new frontiers of innovation for 3D printing.

To the moon and beyond

The global Artemis program is a NASA-led international space exploration program that aims to land the first woman and the first person of color on the Moon by 2025 as part of the long-term goal of establishing a sustainable human presence on the Moon. Additionally, the NASA mission called Europa Clipper, scheduled for a 2024 launch, will orbit around Jupiter and fly by Europa , one of Jupiter’s moons, to study the presence of water and its habitability. China’s mission, Chang’e 6 , plans to bring samples from the moon back to Earth for further studies. The Martian Moons Exploration (MMX) mission by Japan’s JAXA plans to bring back samples from Phobos, one of the Mars moons. Boeing is also expected to do a test flight of its reusable space capsule Starliner , which can take people to low-earth orbit.

The R&D impact of Artemis extends to more fields than just aerospace engineering, though:

• Robotics: Robots will play a critical role in the Artemis program, performing many tasks, such as collecting samples, building infrastructure, and conducting scientific research. This will drive the development of new robotic technologies, including autonomous systems and dexterous manipulators.
• Space medicine: The Artemis program will require the development of new technologies to protect astronauts from the hazards of space travel, such as radiation exposure and microgravity. This will include scientific discoveries in medical diagnostics, therapeutics, and countermeasures.
• Earth science: The Artemis program will provide a unique opportunity to study the Moon and its environment. This will lead to new insights into the Earth's history, geology, and climate.
• Materials science: The extreme space environment will require new materials that are lightweight, durable, and radiation resistant. This will have applications in many industries, including aerospace, construction, and energy.
• Information technology: The Artemis program will generate a massive amount of data, which will need to be processed, analyzed, and shared in real time. This will drive the development of new IT technologies, such as cloud computing, artificial intelligence, and machine learning.

The CRISPR pay-off

After years of research, setbacks, and minimal progress, the first formal evidence of CRISPR as a therapeutic platform technology in the clinic was realized. Intellia Therapeutics received FDA clearance to initiate a pivotal phase 3 trial of a new drug for the treatment of hATTR, and using the same Cas9 mRNA, got a new medicine treating a different disease, angioedema. This was achieved by only changing 20 nucleotides of the guide RNA, suggesting that CRISPR can be used as a therapeutic platform technology in the clinic.

The second great moment for CRISPR drug development technology came when Vertex and CRISPR Therapeutics announced the authorization of the first CRISPR/Cas9 gene-edited therapy, CASGEVY™, by the United Kingdom MHRA, for the treatment of sickle cell disease and transfusion-dependent beta-thalassemia. This was the first approval of a CRISPR-based therapy for human use and is a landmark moment in realizing the potential of CRISPR to improve human health.

In addition to its remarkable genome editing capability, the CRISPR-Cas system has proven to be effective in many applications, including early cancer diagnosis . CRISPR-based genome and transcriptome engineering and CRISPR-Cas12a and CRISPR-Cas13a appear to have the necessary characteristics to be robust detection tools for cancer therapy and diagnostics. CRISPR-Cas-based biosensing system gives rise to a new era for precise diagnoses of early-stage cancers.

MIT engineers have also designed a new nanoparticle DNA-encoded nanosensor for urinary biomarkers that could enable early cancer diagnoses with a simple urine test. The sensors, which can detect cancerous proteins, could also distinguish the type of tumor or how it responds to treatment.

Ending cancer

The immuno-oncology field has seen tremendous growth in the last few years. Approved products such as cytokines, vaccines, tumor-directed monoclonal antibodies, and immune checkpoint blockers continue to grow in market size. Novel therapies like TAC01-HER2 are currently undergoing clinical trials. This unique therapy uses autologous T cells, which have been genetically engineered to incorporate T cell Antigen Coupler (TAC) receptors that recognize human epidermal growth factor receptor 2 (HER2) presence on tumor cells to remove them. This could be a promising therapy for metastatic, HER2-positive solid tumors.

Another promising strategy aims to use the CAR-T cells against solid tumors in conjunction with a vaccine that boosts immune response. Immune boosting helps the body create more host T cells that can target other tumor antigens that CAR-T cells cannot kill.

Another notable trend is the development of improved and effective personalized therapies. For instance, a recently developed personalized RNA neoantigen vaccine, based on uridine mRNA–lipoplex nanoparticles, was found effective against pancreatic ductal adenocarcinoma (PDAC). Major challenges in immuno-oncology are therapy resistance, lack of predictable biomarkers, and tumor heterogenicity. As a result, devising novel treatment strategies could be a future research focus.

Decarbonizing energy

Multiple well-funded efforts are underway to decarbonize energy production by replacing fossil fuel-based energy sources with sources that generate no (or much less) CO2 in 2024.

One of these efforts is to incorporate large-scale energy storage devices into the existing power grid. These are an important part of enabling the use of renewable sources since they provide additional supply and demand for electricity to complement renewable sources. Several types of grid-scale storage that vary in the amount of energy they can store and how quickly they can discharge it into the grid are under development. Some are physical (flywheels, pumped hydro, and compressed air) and some are chemical (traditional batteries, flow batteries , supercapacitors, and hydrogen ), but all are the subject of active chemistry and materials development research. The U.S. government is encouraging development in this area through tax credits as part of the Inflation Reduction Act and a $7 billion program to establish regional hydrogen hubs.

Meanwhile, nuclear power will continue to be an active R&D area in 2024. In nuclear fission, multiple companies are developing small modular reactors (SMRs) for use in electricity production and chemical manufacturing, including hydrogen. The development of nuclear fusion reactors involves fundamental research in physics and materials science. One major challenge is finding a material that can be used for the wall of the reactor facing the fusion plasma; so far, candidate materials have included high-entropy alloys and even molten metals .

Neurodegenerative diseases

Neurodegenerative diseases are a major public health concern, being a leading cause of death and disability worldwide. While there is currently no cure for any neurodegenerative disease, new scientific discoveries and understandings of these pathways may be the key to helping patient outcomes.

• Alzheimer’s disease: Two immunotherapeutics have received FDA approval to reduce both cognitive and functional decline in individuals living with early Alzheimer's disease. Aducannumab (Aduhelm®) received accelerated approval in 2021 and is the first new treatment approved for Alzheimer’s since 2003 and the first therapy targeting the disease pathophysiology, reducing beta-amyloid plaques in the brains of early Alzheimer’s disease patients. Lecanemab (Leqembi®) received traditional approval in 2023 and is the first drug targeting Alzheimer’s disease pathophysiology to show clinical benefits, reducing the rate of disease progression and slowing cognitive and functional decline in adults with early stages of the disease.
• Parkinson’s disease: New treatment modalities outside of pharmaceuticals and deep brain stimulation are being researched and approved by the FDA for the treatment of Parkinson’s disease symptoms. The non-invasive medical device, Exablate Neuro (approved by the FDA in 2021), uses focused ultrasound on one side of the brain to provide relief from severe symptoms such as tremors, limb rigidity, and dyskinesia. 2023 brought major news for Parkinson’s disease research with the validation of the biomarker alpha-synuclein. Researchers have developed a tool called the α-synuclein seeding amplification assay which detects the biomarker in the spinal fluid of people diagnosed with Parkinson’s disease and individuals who have not shown clinical symptoms.
• Amyotrophic lateral sclerosis (ALS): Two pharmaceuticals have seen FDA approval in the past two years to slow disease progression in individuals with ALS. Relyvrio ® was approved in 2022 and acts by preventing or slowing more neuron cell death in patients with ALS. Tofersen (Qalsody®), an antisense oligonucleotide, was approved in 2023 under the accelerated approval pathway. Tofersen targets RNA produced from mutated superoxide dismutase 1 (SOD1) genes to eliminate toxic SOD1 protein production. Recently published genetic research on how mutations contribute to ALS is ongoing with researchers recently discovering how NEK1 gene mutations lead to ALS. This discovery suggests a possible rational therapeutic approach to stabilizing microtubules in ALS patients.

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