**2. Limitations of ART**

Despite its significant role in the prevention of HIV-1 infection transmission, there are several social, economic, and technical obstacles associated with ART therapy.

Besides coping with social stigma for ART [6], there is the social and economic challenge of the limited availability of ART therapy in low-income countries [7]. Given that the countries most affected by HIV are resource poor, only a small proportion of people of the global population with HIV have benefited ART [3]. Despite scaling up ART in several of these countries of sub-Saharan Africa, there are still countries where less than 25% of the adult population has access to ART [2]. Additionally, there is limited screening, so people may be unaware of their positive HIV status and never enroll in ART therapy [2].

The technical shortcomings of ART include the following: (i) limited impact on latent reservoir, (ii) strict, daily adherence to drug regimen, (iii) requirement of lifelong treatment, (iv) negative effect on immune cells, (v) drug adverse effects, (vi) drug-drug interactions, and (vii) drug resistance [7, 8].

Notably, if ART is started promptly in initial stages of infection, the latent reservoir is significantly reduced in size, but this reservoir is never completely eradicated [8, 9]. Regardless of the initiation of ART, the latent reservoir of HIV-1 infected cells is a momentous challenge in terms of limited immune response and potential for drug or vaccine treatment.

Lifelong treatment is necessary for continued viral load suppression and for the prevention of transmission to sexual partners, but there are some negative inevitable health consequences. Chronic inflammation and altered tissue architecture in lymph nodes and gastrointestinal tract occur on ART. This has significant repercussions on the functionality and survival of immune cells [8]. Additionally, long-term use is also associated with cardiovascular diseases, cancer, liver disease, long-term peripheral and central nervous complications, renal and metabolic disorders, and osteoporosis [4].

The adverse effects of ART drugs include insulin resistance, lipodystrophy, and dyslipidemia [8] and may lead to patient noncompliance. Additionally, given the barriers to accessibility, it may cause patients to be noncompliant and lead to issues with drug resistance [7].

Because of the difficulties of medication compliance, other ART drug deliveries are being tested in clinical trials, like long-acting injectable antiretrovirals, implantable devices, and vaginal rings [6]. Currently, there are long-acting injectable ART delivered by injections every two months being studied. The injection regimen increased patient adherence as compared to daily oral pills but has yet to be fully complete drug approval and implementation processes. Further research is aimed to extend the duration between injections to once yearly or twice a year [10].
