Since 1996, Brazilian Ministry of Health Law 9.313/96 (Brasil, 1996) has guaranteed free access to ART to treat HIV/AIDS, thereby lowering mortality and morbidity and contributing to improving the quality of life of people living with HIV (PLHIV) (Lima et al., 2012).

On average, 40,000 new HIV/AIDS cases have been recorded every year since 2011. In the Federal District (DF), 10,735 cases (7,903 men and 2,832 women) were reported between the first notification of the disease in 1985 and December 2017. In 2017 alone 645 new cases were recorded, a significant increase compared to previous years (SES-DF, 2018; MS, 2021).

The increase in ART effectiveness against HIV infection in the last 30 years is a landmark for global science, transforming a highly lethal acute disease into a chronic condition, with a reduction in viral transmission both congenitally and through sexual contact, over a short time period. The success of ART in suppressing viral replication, however, is directly associated with patient adherence to treatment (Trickey et al., 2017; Melo et al., 2018).

Treatment adherence is a dynamic multifactorial process involving the behavior of PLHIV, according to the treatment indicated by the health professional, using the drugs at specified doses and times, undergoing laboratory tests and periodically accessing specialized health services (da Silva et al., 2022). The extrinsic and intrinsic factors of adherence are adverse drug reactions, professional attention in guiding the therapeutic plan, access to drug dispensing units (DDU) (extrinsic) and socioeconomic conditions, psychological status, physical or cognitive limitations (intrinsic) (da Silva et al., 2022).

Studies demonstrate that there is no statistically significant difference in the likelihood of virological failure between PLHIV who achieve 95%–100% adherence and those with 80%–95%, suggesting that even the latter can suppress viral replication and not develop ART resistance (Bezabhe et al., 2016; Miyada et al., 2017).

The aim of the present study was to compare treatment adherence and viral load (VL) suppression with the evolution of the protocols and other associated factors in PLHIV who received ART at a DDU in the DF and participated in longitudinal studies conducted in three different guideline periods for the care of adults infected by HIV.

The composition of the three databases used in the study is presented in Figure 1. The databases contained 790 PLHIV. The inclusion and exclusion criteria resulted in 268 people being excluded for the different reasons described. The final sample size was 522 PLHIV.

The 522 PLHIV included a majority (75.1%) of men, with an average age of 40.6 years (standard deviation of 10.8 years), as shown in Table 2. In period 1, only 129 individuals (37.8%) had preferential initial ART (AZT+3TC + EFZ), according to the recommendation used at the time (2008), while for periods 2 and 3, it was an inclusion criterion, that is, 100% of patients underwent preferential initial ART according to the respective protocol. ART was modified in 102 PLHIV during the three periods, with a total of 126 alterations (Table 2). The average percentage of ART adherence across all three periods was 90.7%, with PLHIV in period 2 exhibiting the best adherence (92.4%) (Table 2).

The highest percentage of VL suppression (88.9%) occurred in period 3 (Table 3). This variables had an important missing data, with participants with no viral load examination records in the system. There were 28% of subjects without information for initial VL and 33.5% for final VL.

Analysis of adherence in relation to the independent variables showed a significant difference when changes in antiretroviral therapy occurred (p = 0.031). There was greater adherence in women, but lower for those aged between 18 and 29 and 40–49 years (Table 4).

In relation to final VL (Table 5), the lower VL suppression was significant in patients who changed their ART (p= <0.001| RR 1.32; 95%CI 1.07–1.63) and higher in those with initial VR values less than 100,000 copies/mL (p = 0.01) and individuals with optimal (>95%) and good (80%–95%) treatment adherence (p= <0.001). It is important to note that PLHIV with low adherence (<80%) exhibited a nearly two-fold higher risk of not suppressing VL (RR 1.83; 95% CI 1.37–2.34) compared to those with optimal and good adherence (above 80%). The 18-29-year age group exhibited a higher percentage of detectable final VL (Table 5) than that of the other age groups, albeit not statistically significant.

This study analyzed the treatment adherence and VL suppression of PLHIV using ART treatment at a DDU, based on the data from three studies that occurred at the same service but at different times, describing the evolution of guidelines for the care of adults with HIV in Brazil (Cunha, 2014; Fagundes, 2017; Batista, 2018). No other literature studies were found that compared and analyzed ART adherence and viral suppression at three different periods, when recommendations or clinical protocols for HIV/AIDS were implemented in the country.

The study showed that PLHIV with low adherence exhibited a two-fold higher risk of not suppressing VL with the use of ART than those with optimal or good adherence. In our findings, adherence above 80% achieved viral suppression in around 90% of the population, results compatible with a previous meta-analysis (Pacheco et al., 2019). The goal proposed by UNAIDS, denominated 90–90–90 (90% of infected people should be diagnosed, 90% should be in treatment and 90% should reach viral suppression), is feasible if countries achieve good adherence rates (Nachega et al., 2016).

A predominance of men was found in the PLHIV studies, in all the periods, with a marked decline in women in periods 2 and 3. The decrease in new cases among women has been reported in national epidemiological data, with an increase in the men: women ratio to 2.3 in 2018 (MS, 2021), and also described in the international literature (WHO, 2019).

With respect to age group, there was a change in HIV incidence in younger people. In period 1, around 40% of PLHIV were aged between 18 and 39 years, while in periods 2 and 3 the percentage doubled (around 75% and 80%, respectively). This change in the profile of new PLHIV is attracting attention in HIV/AIDS treatment adherence studies, especially in adolescents and young people in peripheral areas, due to the risks that these age groups are exposed to, such as social vulnerability, injectable drug sharing, and unprotected sex, among others (Dunn et al., 2018; Taquette and Rodrigues, 2019). In addition, this population exhibited a concerning higher viral load at the end of the study period. Specific care strategies are needed for this population in order to reduce the impact of HIV/AIDS in the coming decades (MS, 2019; WHO, 2019).

Over time, there has been a change in the clinical profile of PLHIV who use ART in Brazil, according to each new guideline adopted by the Ministry of Health. In terms of therapeutic schemes, in periods 2 and 3, the preferential scheme was the inclusion criteria, as determined by PCDT-2013 and its update in 2017. In period 1, in addition to PLHIV in previous treatment, the 2008 recommendation did not mandate ART as the recommended scheme or justify ART changes on the Drug Request Form, as occurred after PCDT-2013, which explains the low percentage of the preferential scheme during this period (Pavlos and Phillips, 2011).

There was better ART adherence in period 2 (92.4%) than in the other periods. Our results demonstrated that introducing a combined fixed dose, such as tenofovir, lamivudine and efavirenz (TDF/3TC/EFZ), administered once a day, improved adherence. As reported in the literature, simpler dosing schemes, with fewer administrations and unique dosage forms favor adherence (Bisson et al., 2008; Cotte et al., 2017; Costa et al., 2018; Altice et al., 2019). Furthermore, intrinsic and extrinsic factors may affect treatment adherence (Toledo et al., 2019).

Viral load suppression was higher in period 3 (88.9%), despite its lower adherence rate in relation to the other periods. One of the main changes in PCDT-2017 was replacing EFZ with dolutegravir (DTG) in the preferential scheme for initial treatment of PLHIV or in cases of people with EFZ-related adverse reactions (MS, 2018; Benzaken et al., 2019; MS, 2021). The results suggest that the scheme containing DTG is more effective than the earlier first-line schemes (Batista et al., 2019). International studies and guidelines suggest that the use of DTG in ART achieved good viral load suppression in six months, with a low percentage of adverse reactions and scheme changes (Corado et al., 2018). However, other studies have shown an increasing number of adverse events attributed to DTG (neuropsychiatric symptoms, weight gain and systemic hypersensitivity reactions) (Scévola et al., 2020).

Also significant was the relation between viral suppression for PLHIV and initial VL up to 100,000 copies and treatment adherence. PCDT-2017 recommended that ART be prescribed as soon as HIV is diagnosed. This recommendation was based on evidence that viral suppression is faster with early treatment (Bigna et al., 2016). The “non-transmissible” concept proposed by the Ministry of Health (MS, 2019), can be used for PLHIV in treatment exhibiting undetectable VL examinations for more than six months, according to the literature, used as the basis for this new concept (Rodger et al., 2019). This information reinforces the importance of ART adherence as a means of preventing HIV, thereby avoiding transmission of the virus and gradually reducing the budgetary impact on the health system (Pacheco et al., 2019).

Study limitations include the fact that around 30% of participating PLHIV had no VL registered in SISCEL, after the onset of ART, which may have produced biased results. Some of the individuals may have undergone examinations in private laboratories and these data were not included in SISCEL, which may compromise future research on strategic public health measures for PLHIV (Benzaken et al., 2019; Focaccia et al., 2019; Meireles et al., 2019). Adherence was measured using the pharmacy dispensing register, which, despite being used in other Brazilian studies, exhibits limitations (Gachara et al., 2017). Moreover, the Medical records contain incomplete sociodemographic and clinical information, even for the most recent period, thereby hindering analyses of other independent variables.

Adherence is an important factor in achieving effective treatment for chronic conditions, such as HIV/AIDS. Simplified therapeutic schemes consisting of a combined fixed single tablet dose, such as in the TDF/3TC/EFZ scheme used in the second period of the study, favor treatment adherence. However, despite the lower adherence (>80%), treatments containing dolutegravir seem to promote and maintain viral suppression in around 90% of PLHIV. Based on these results, adherence above 80% achieves effective viral suppression in therapeutic schemes involving efavirenz and dolutegravir.