CLINICAL MATTERS

One of the most sought-after vaccines in medicine is the HIV vaccine. When HIV was first discovered in 1981, scientists were optimistic that they would be able to develop a vaccine in a few years. More than 40 years later and after millions of people have died from AIDS, an effective HIV vaccine remains elusive. Antiretroviral treatment has enabled many persons with HIV to live normal lives but they still need to take their medicines every day and there is always the risk of development of drug resistance. The cost and the side effects of the medication remain significant burdens, not to mention the social stigma that remains prevalent with an HIV diagnosis.

In the Philippines, an estimated 180,000 people are living with HIV. Only 60 percent of them have been diagnosed and only 60 percent are on life-saving antiretroviral treatment. As of Aug. 2024, nearly 12,000 Filipinos have been diagnosed with HIV this year and we are on track to have the highest number of cases ever recorded for a calendar year. While new HIV infections worldwide are down by 40 percent since 2010, the Philippines has increased its yearly HIV infection rate by nearly 300 percent. Our HIV epidemic is one of the fastest growing in the world. While there have been many improvements in access to care and life-saving treatment, it cannot be business as usual since more and more lives are at stake. Until a cure is found, the only way to stem the tide is to prevent more infections from occurring. 

Why is HIV so difficult to cure? When the virus enters the cell, it converts its RNA (it is a retrovirus) into DNA which it then inserts into the host genome. That means that every time the host cell reproduces, the virus gets replicated along with it. For long-lived cells of the body that are infected, this proviral DNA can at any time become an active virus that can quickly make more viruses. This means that there are cells that remain a constant source of infection even if you could somehow eliminate every single active virus with treatment. 

To date, there are seven instances of documented HIV cures, but these occurred under extraordinary circumstances. All of these patients received bone marrow or stem cell transplants to treat an underlying cancer. Some of the stem cells came from donors with special mutations that make them resistant to HIV infection. These cures are not at all practical since stem cell transplants carry a high mortality rate and would not have beengivenif there had not been a life-threatening condition that needed treatment. Moreover, this method of curing HIVdoesn’t always work since many morepersons with HIV who underwent the same procedures did not get cured. The fact that a true cure can sometimes be achieved is encouraging, but we are still far from a practical and readily replicable cure for HIV.

HIV is one of the fastest mutating viruses in the world. It mutates a million times faster than bacteria and produces many different versions of itself even within one infected person. This extreme diversity makes it impossible for the body’s immune system to keep up with the changes. This diversity is also the same reason why it has been so difficult to produce an effective vaccine. A vaccine that is effective against one form of the virus may not work against mutated forms. One strategy has been to use two different vaccine types to see if enough kinds of antibodies and immune cells that cover that diversity are made. This strategy seemed promising, with a combination vaccine regimen that was marginally effective when used in Thailand. Unfortunately, a more recent trial using a similar strategy in Africa failed to show any significant protection from HIV infection.

Nevertheless, scientists aren’t giving up on finding an effective HIV vaccine. With the advances in vaccinology developed during the Covid-19 pandemic, there are more and more options to explore in terms of vaccine targets and technologies for implementation. mRNA vaccines have revolutionized what people thought were possible in terms of what could be targeted and how robust an immune response could be induced. Though it will take years for these efforts to bear fruit and we need something to stop infections much more urgently especially in our country.

Traditionally, HIV prevention has taken the form of either pharmacologic ornon-pharmacologic intervention. Nonpharmacologic interventions include the use of condoms, proper sexuality education, abstinence, and modification of risky behavior such as avoiding the use of intravenous drugs or not having multiple sexual partners. Pharmacologic interventions include the use of topical microbicides, vaginal rings releasing antiretroviral medicine, and most recently pre-exposure prophylaxis or PrEP. In addition, people with HIV who are on antiretroviral treatment and have successfully suppressed their virus are no longer capable of infecting other people. This strategy, known as U=U or undetectable equals untransmissible, is an important public health intervention that recognizes thebenefit of putting people on treatment not just to prolong their lives but also to prevent them from infecting other people.

Out of all these interventions, the one that is underutilized and currently being promoted by the World Health Organization and UNAIDS is the use of PrEP. PrEP, when taken correctly and consistently can decrease the risk of acquiring HIV through sex by over 99 percent. Unfortunately, most people are bad at taking medicine over a long period of time. PrEP is not offered to everyone and is only indicated for those with the highest risk of acquiring HIV. In addition, PrEP does not prevent other sexually transmitted infections and so using a condom withPrEP is encouraged. The Philippines, with the help of the Global Fund has been making some headway in rolling out PrEP locally, but adherence to a daily regimen is quite challenging. An alternative form of PrEP known as PrEP on demand is also effective, but still involves taking several courses of pills.

Most recently, the HIV community has been very excited about a new PrEP drug called lenacapavir. This is an injectable form of PrEP that only needs to be given every six months. In trials among cis-gendered women in Africa, lenacapavir given every 26 weeks prevented 100 percent of HIV infections and was superior to oral PrEP. In trials among men who have sex with men and transgendered women, twice-a-year injectable lenacapavir prevented 96 percent of HIV infections, and was 89 percent more effective than oral PrEP. This makes lenacapavir almost a de-facto HIV vaccine, albeit one that kills the virus directly and does not use the immune system to do its work.

Being a new drug, it is expected that injectable lenacapvir will be quite expensive. Fortunately, manufacturers of HIV antiretroviral drugs have historically recognized that many resource-limited settings cannot afford their drugs even as they seek to save the lives of their people. In partnership with UNAIDS, these companies have drastically dropped the prices of their medicines for countries like ours. For instance, ViiV, the maker of dolutegravir, has licensed their drug to lower-middle income countries (LMICs) for $50 a year, a far cry from what they charge in developed countries. Gilead, the maker of lenacapvir, has pledged to make this drug affordable as PrEP for LMICs and the Philippines, with its sky-high rate of infection, is among their priority countries for this intervention. If this comes to fruition, we will have a potentially game-changing drug that will put our country back on track in controlling our HIV epidemic.