Advances in HIV Management: Where Are We Going?

In the last two decades, HIV management has gone from being a strictly antiretroviral treatment to becoming a comprehensive health strategy that seeks sustained virological suppression, the reduction of associated morbidity and mortality, the improvement of the quality of life of those affected, and a tool to restrict viral reproduction and control existing epidemiological transmission.

Treatment

A crucial development in the evolution of core therapy has been the transition to simple fixed-dose regimens and simplified adherence, such as one-day regimens or even weekly dosing in certain combinations, which have increased adherence and the likelihood of maintaining an undetectable viral load. Viral suppression not only protects the person living with HIV, but also significantly reduces the risk of transmission, bringing the “test and treatment” goal as a public health tool closer.

Antiretroviral therapy (ART) continues to evolve with the introduction of more tolerable regimens that are less affected by drug interactions, and with improved safety profiles. In clinical practice, priority is given to fixed-dose regimens, a lower load on the number of pills or tablets, and fewer adverse effects, which facilitates long-term adherence. In addition, the management of second- and third-generation ART has gained in sustained activity and resilience to resistance, thanks to the development of powerful and robust drugs of good acceptance and tolerability, which allow regimen changes without losing viral suppression. This progress is closely linked to more proactive clinical surveillance that includes viral load controls, kidney and liver functions, lipids, and rates of metabolic comorbidities, adapting treatment to the presence of co-infections, pregnancy and considerations of interactions with other drugs.

The eradication of HIV transmission is increasingly plausible, driven by evidence that undetectable viral load virtually eliminates sexual transmissibility or U=U (undetectable-untransmittable). This concept has driven TasP (Treatment as Prevention) programs, and has modulated primary care approaches, screenings aimed at high-risk populations, and harm-reduction strategies. However, to achieve sustainable results, it’s critical to address structural barriers such as stigma, unequal access to health services, drug costs, and geographic disparities. Equity in access to ART, diagnostic testing, and psychosocial support services is crucial to sustaining population benefits and preventing viral load flare-ups at the community level. Treatment guidelines from the U.S. Department of Health and Human Services (DHHS), the International Antiviral Society-USA (IAS), and the European Clinical Society (EACS) establish, as a preference, the treatment approach based on 1-2 nucleosides (NRTI) PLUS an integrase inhibitor (INSTI) as the preferred treatment for most patients. These treatments have provided the central axis of initiation and replacement for a large majority of cases as far as therapy is concerned.

Prevention

In terms of prevention, vaccines aimed at stimulating the immune system to develop neutralizing antibodies against the virus remain somewhat elusive and limited. And while there’s a pressing interest in the development of injectable monoclonal antibodies as agents used in combination to keep the virus under control by stimulating the immune system for the development of neutralizing antibodies capable of controlling the virus without the need for ART, we’re not yet ready for the commercialization of these at this time.

Nevertheless, it should be noted that pre-exposure prophylaxis (PrEP) strategies and prenatal and postnatal preventive therapies have shown a significant impact on the incidence of new infections worldwide. In addition, the future outlook is very encouraging. With the recent approval of long-acting injectable drugs every 2 months, twice a year, and potentially once a year, this prophylaxis and treatment is becoming viable for many people. Needless to say, if these drugs are made available generically to all vulnerable and at-risk populations globally, this would represent a revolutionary turning point as a giant step towards the control and potential eradication of HIV.

Among the current challenges to be faced, there is a need to optimize management in vulnerable populations, including people who use substances, younger populations, rural communities, and groups with sociocultural barriers, to ensure adherence and continuity of care. Likewise, benefits in adherence and monitoring have been shown by expanding the availability of preventive antiretroviral (PrEP) drugs, the implementation of digital health systems, telemedicine and pharmaceutical reminders, especially in settings with limited access.