Abstract
Background
Optimization of antiretroviral therapy (ART) is one of the key recommendations of the World Health Organization (WHO) since 2019 to achieve 95% viral suppression. The transition to optimized therapeutic regimens (OTRs) in pediatrics began in Cameroon at 2020. The objective of our study was to evaluate the impact of OTRs on HIV-infected adolescents (HIA) in healthcare facilities in the city of Douala.
Methods
A multicenter cross-sectional study was conducted from February to June 2022 in five hospitals in Douala. All HIA aged 10–19 years receiving ART for at least six months were included. Sociodemographic, clinical, therapeutic, and data related to the transition to optimized regimens were collected. Statistical analyses were performed using SPSS version 25. A p-value < 0.05 was considered statistically significant.
Results
Out of the 613 adolescents on antiretroviral therapy (ART), 599 (97.7%) were included in the study at a median age of 15 years (interquartile range [IQR]: 13–18 years). The male-to-female ratio was 0.9, and most adolescents (94.0%) had acquired HIV through mother-to-child transmission. Among the 599 HIV-infected adolescents (HIV), 391 (65.3%) were receiving optimized therapy, with a mean ART duration of exposure of 11.6 ± 5.7 months. Before switching to optimized therapy, 329 adolescents (84.2%) had viral suppression, compared to 370 (94.6%) after switching. Adolescents receiving optimized antiretroviral therapy were significantly 3.3 times more likely to have viral load suppression (OR: 3.3; 95% CI: 2.0–5.6; p < 0.001). These optimized regimens significantly reduced moderate malnutrition (OR: 0.38; 95% CI: 0.16–0.91; p = 0.042) and improved nutritional status, with mean weight increasing from 43.2 ± 13.0 kg to 46.7 ± 13.3 kg (p < 0.001) and body mass index increasing from 18.8 ± 3.2 to 19.6 ± 3.0 kg/m² (p < 0.001).
Conclusion
Optimized antiretroviral regimens significantly improved viral suppression and moderate malnutrition among HIV infected adolescents in Douala, Cameroon.
Keywords: HIV infected adolescents, antiretroviral therapy, optimization; Viral load; Nutritional status; Cameroon
Introduction
Adolescents and young people make up a growing proportion of individuals living with human immunodeficiency virus (HIV). Approximately 1.5 million adolescents aged 10 to 19 are living with HIV globally, with 140,000 newly infected with HIV, including 18,000 in West and Central Africa in 2023. In that same year, 65% of adolescents living with HIV were on antiretroviral therapy (ART), including 58% in West and Central Africa [1, 2]. Girls were the most affected, representing 70% of the total number of adolescents living with HIV [1, 2]. Unfortunately, 24,000 adolescents living with HIV died from AIDS-related illnesses in 2023, including 7,800 in West and Central Africa, making HIV the second leading cause of death among adolescents worldwide [2].
Progress in HIV prevention and treatment among children and adolescents remains low compared to adults due to poor implementation of screening strategies, insufficient access to pediatric HIV care, and a lack of uptake of World Health Organization (WHO) recommendations, which are poorly understood by practitioners responsible for prescribing suboptimal ART regimens, leading to the emergence of ARV resistance [3].
In Cameroon, ARV coverage among children aged 0 to 14 years was 35% (11,531/33,085) and among adolescents aged 10 to 19 years was 40% (11,873/30,467), compared to 81% among adults in 2021, thus highlighting a strong disparity between adults and children/ adolescents HIV care [4–6]. The introduction of antiretroviral with a high genetic barrier to ART resistance and the development of new recommendations based on optimized treatment regimens have been implemented to achieve UNAIDS (Joint United Nations Programme on HIV/AIDS) ' global target of 95% viral suppression [6]. The revision of the national guidelines for the management of Children and Adolescents in Cameroon included the effective introduction of Dolutegravir (DTG) into the protocols for the care of children and adolescents in 2020. Despite recent progress in access to pediatric ART, reaching the 95% viral suppression target remains challenging without access to effective, age-appropriate formulations in resource-limited countries. Key barriers include limited availability of age-appropriate pediatric drug formulations, palatability issues with liquid preparations, dosing complexity due to weight-based adjustments, supply chain constraints affecting the availability of fixed-dose combinations, caregiver adherence challenges, and insufficient access to routine pediatric viral load monitoring [7]. Optimized ART involves a treatment regimen with a better-tolerated, age-appropriate formulation, prescribed at the correct dose, ensuring better adherence and long-term viral load suppression [8, 9].
A trial conducted in the United Kingdom in 2021 involving HIV-infected children and adolescents initiated on first- or second-line DTG-based ART demonstrated the efficacy of OTRs compared to standard regimens [9]. The potential efficacy of the optimized DTG-based treatment regimen in HIV-infected adolescents who did not respond to first- and second-line ART, with a 58% viral suppression rate in HIV-infected adolescents, was reported in Zimbabwe in 2019 [10]. In Cameroon, there is limited data available since the implementation of new guidelines on ART optimization in adolescents. The aim of our study was to evaluate the impact of ART optimization in HIV-infected adolescents in hospitals in the city of Douala.
Methods
Study design and type
A multicenter cross-sectional study was conducted from February to June 2022 over a five-month period among HIV infected adolescents aged 10–19 years receiving ART in five HIV care facilities in Douala. Douala is the economic capital of Cameroon and had approximately 4 million inhabitants in 2022, considered the most populated city in the country, with a population growth rate of more than 3% per year. The Littoral Region comprises 24 health districts. Specialized HIV services including viral load testing are available at secondary- and tertiary-level facilities.
Cameroon’s healthcare system is structured into three levels (central, intermediate, and peripheral) comprising seven categories of healthcare facilities. The central (tertiary) level consists of Category 1 hospitals (general hospitals offering advanced care, research, and specialized training) and Category 2 hospitals, focused on high-level referral care. The intermediate (secondary) level includes Category 3 hospitals: regional hospitals that coordinate district activities at the regional level. The peripheral (primary) level provides local care and consists of Category 4 health facilities: (i) District Hospitals (DHs), responsible for a specific geographic area, offering general care and emergency services; (ii) Category 5 District Medical Centers (DMCs), which serve as referral centers for integrated health centers; (iii) Category 6 Integrated Health Centers, focused on primary healthcare; (iv) outpatient health centers, category 7, for local care.
HIV services, including antiretroviral therapy, are available at all levels, while viral load testing are conducted at secondary- and tertiary-level facilities. Study sites were selected based on the size of their adolescent HIV cohort, with eligibility requiring follow-up of at least 50 HIA, and to ensure representation of different levels of the healthcare pyramid. The selected facilities included one secondary-level referral hospital (Laquintinie Hospital of Douala), three district hospitals (Bonassama District Hospital, Nylon District Hospital, and Deïdo District Hospital), and one fifth-level healthcare facility (Soboum District Medical Center).
Study population and sample size
All HIA aged 10–19 years who had been receiving ART for at least six months and were followed up in the participating facilities were eligible for inclusion. Assuming an estimated prevalence of ART coverage among adolescents in Cameroon of 35.2% in 2020 [11], a minimum sample size was calculated using Cochran’s formula [12]: n = Z² × p (1 − p) / e², where Z = 1.96 (for a 95% confidence level), p = 0.352 and e = 0.05 (5% margin of error), hence a minimum required sample size of 351.
N (minimum sample size) = (1.96)2 × 0.352 (1-0.352) / (0.05)2 = 351
Study procedure
A census was conducted in the ART registries at the 5 study sites to identify all HIV-infected adolescents who had been on ART for at least 6 months. Patients who had received antiretroviral treatment for less than six months and those who were lost to follow-up were excluded from our study. After obtaining informed consent from the adolescents’ parents or guardians in accordance with national guidelines, data was collected using a standardized questionnaire through interviews with adolescents or their caregivers, when necessary, and review of medical records.
Data variables, sources of data, and data collection
Data were collected from three main sources: (i) structured questionnaires administered through face-to-face interviews with adolescents or their caregivers; (ii) review of medical records including ART registries and patient files; and (iii) clinical measurements performed during routine consultations. The variables collected included: sociodemographic characteristics (age, sex, education level, and family status including orphan status and living arrangements), clinical characteristics (age at the time of HIV diagnosis, mode of transmission, anthropometric measurements including weight, height, and body mass index (BMI) before and after ART optimization), therapeutic information (initial ART regimen, reasons for regimen change, and current ART regimen), and biological data (viral load at the time of treatment regimen changes and current status). Optimized Treatment Regimens (OTR) were defined according to the revised national guidelines for the management of Children and Adolescents guidelines (2020), aligned with WHO 2019 recommendations, as follows: first-line OTR consisted of TDF/3TC/DTG or ABC/3TC/DTG; second-line OTR consisted of TDF/3TC/DTG (for patients failing ABC-based first-line) or ABC/3TC/LPV/r (for younger adolescents unable to receive DTG). Regimen modifications due to drug stock-outs were classified separately as pragmatic substitutions and were not considered as OTR in this analysis. HIV viral load suppression was defined as a viral load < 1,000 copies/mL, in accordance with WHO guidelines [13].
Nutritional status was assessed in all adolescents to monitor potential adverse effects of DTG. Anthropometric evaluation was based on WHO growth standards, including weight-for-age, height-for-age, and BMI, calculated as weight (kg) divided by height squared (m²). Nutritional status was classified using WHO reference growth charts for children and adolescents aged 5–19 years [14].
Statistical analysis
Data were entered independently by two trained research assistants using Microsoft Excel 2013 (double data entry) and cross-checked for discrepancies. Range and logic checks were applied to detect implausible values (e.g., age outside 10–19 years, viral load values outside expected ranges). Missing or duplicate entries were identified and resolved through consultation with the original medical records. Excel’s data validation tools were used to restrict input formats for key variables. Data were analyzed using SPSS version 25. Quantitative variables were summarized as means ± standard deviation or medians with interquartile ranges, while categorical variables were presented as frequencies and percentages. Comparisons between categorical variables were performed using the Chi-square test, and paired Student’s t-tests were used to compare continuous variables. Statistical significance was set at p < 0.05.
Ethical considerations
Ethical clearance was obtained from the Institutional Ethics Committee for Research on Human Health of the University of Douala (N°:2992 CEI-UDO / 06/2022 / T). Our study was carried out in strict compliance with the fundamental principles of medical research.
Results
Study population
Among the 613 HIV-infected adolescents (HIA) receiving antiretroviral therapy (ART) who were identified in the participating facilities, 599 (97.7%) were included in the study. Fourteen adolescents (2.3%) were excluded, including two who had been receiving ART for less than six months and twelve who were lost to follow-up.
Participants were recruited from five healthcare facilities: Laquintinie Hospital of Douala (LHD) accounted for 306 adolescents (51.1%), Nylon District Hospital (NDH) for 90 (15.0%), Bonassama District Hospital (BDH) for 78 (13.0%), Deïdo District Hospital (DDH) for 68 (11.3%), and Soboum District Medical Center (SDMC) for 57 (9.6%) (Fig. 1).
Fig. 1.
Flowchart of HIV-infected adolescents on ART in the study. Legend. HIA: HIV-infected adolescents, DLH: Douala Laquintinie hospital, NDH: New-Bell District hospital; DDH: Déido District hospital; BDH: Bonassama District hospital; SDMC: Soboum District Medical Center
Sociodemographic, clinical, and therapeutic characteristics
More than half of the study population were female (312/599; 52.1%), with a sex ratio of 0.92. The median age was 15 years (interquartile range [IQR]: 13–18), and adolescents aged 15–19 years accounted for 331 participants (55.3%). Most adolescents (471/599; 78.6%) were attending secondary school, while 110 (18.4%) had primary-level education.
Among the 599 adolescents, 129 (21.5%) were living with both parents, 207 (34.6%) with their mother, and 71 (11.8%) with their father. Nearly one-third (190/599; 31.7%) were living with a family member other than a biological parent, one adolescent (0.2%) was living alone, and one (0.2%) was living in an orphanage.
Overall, 254 adolescents (42.4%) were orphans, including 129 (50.8%) maternal orphans, 67 (26.4%) paternal orphans, and 58 (22.8%) double orphans (Table 1).
Table 1.
Baseline characteristics of the study population
| Variable | Number (n) | Percentages (%) |
|---|---|---|
| Sex | ||
| Male | 287 | 47.9 |
| Female | 312 | 52.1 |
| Age (years) | ||
| Median (IQR) | 15 (13–18) | — |
| 10–14 | 268 | 44.7 |
| 15–19 | 331 | 55.3 |
| Educational level | ||
| Primary | 110 | 18.4 |
| Secondary | 471 | 78.6 |
| Higher education | 14 | 2.3 |
| Not in school | 4 | 0.7 |
| Family status | ||
| Not orphaned | 345 | 57.6 |
| Orphaned (mother deceased) | 129 | 21.5 |
| Orphaned (father deceased) | 67 | 11.2 |
| Orphaned (both parents deceased) | 58 | 9.7 |
Legend. IQR Interquartile range, HIA HIV-infected Adolescents
The median age at HIV diagnosis was 4.7, IQR [1.5-9] years and 563 (94.0%) HIA had acquired HIV through vertical transmission, 11 (1.8%) through sexual contact, 6 (1.0%) through contaminated blood products and for 19 (3.2%) cases the origin of transmission was unknown.
Antiretroviral regimens at ART initiation and prior to optimization
At ART initiation, 530 adolescents (88.5%) were receiving first-line regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with one non-nucleoside reverse transcriptase inhibitor (NNRTI), mainly nevirapine or efavirenz. Fifty adolescents (8.3%) initiated ART with a first-line regimen containing two NRTIs plus a ritonavir-boosted protease inhibitor (PI/r), and 19 (3.2%) were initiated directly on an optimized integrase inhibitor–based regimen. Only 63 adolescents (10.5%) received regimens containing stavudine or didanosine at ART initiation. During follow-up, 571 adolescents (95.3%) experienced at least one ART regimen change, including 202 (33.7%) who were switched to second-line therapy combining two NRTIs with a PI/r (Table 2).
Table 2.
Distribution of HIA according to the therapeutic protocol at the initiation of ART and before the transition to optimized therapeutic regimens
| Variables | Number (n) | Percentages (%) |
|---|---|---|
| Initial AR T ( n = 599) | ||
| AZT/3TC/NVP | 208 | 34.7 |
| ABC/3TC/ (EFV or NVP) | 138 | 23.0 |
| TDF/3TC/EFV | 78 | 13.0 |
| AZT/3TC/EFV | 49 | 8.2 |
| D4T/3TC/ (EFV or NVP) | 56 | 9.4 |
| AZT/3TC + LPV/r | 29 | 4.9 |
| ABC/3TC + LPV/r | 11 | 1.8 |
| (TDF ou ABC)/3TC/DTG | 19 | 3.2 |
| Others* | 11 | 1.8 |
| Change in protocol during ART ( n = 599) | ||
| No | 28 | 4.7 |
| Once | 179 | 29.9 |
| Twice | 249 | 41.6 |
| Three times | 114 | 19.0 |
| Four times | 29 | 4.8 |
| Transition to an optimized regimen ( n = 599) | ||
| Yes | 391 | 65.3 |
| No | 208 | 34.7 |
| First-line ART regimen before transition ( n = 366) | ||
| AZT/3TC + EFV | 12 | 3.3 |
| ABC/3TC/EFV | 83 | 22.7 |
| ABC/3TC/NVP | 8 | 2.2 |
| TDF/3TC/EFV | 256 | 69.9 |
| AZT/3TC/NVP | 7 | 1.9 |
| Second-line ART regimen before transition ( n = 25) | ||
| ABC/3TC/LPV/r (or ATV/r) | 9 | 36.0 |
| TDF/3TC + LPV/r (or ATV/r) | 13 | 52.0 |
| AZT/3TC/LPV/r | 3 | 12.0 |
Legend. ART Antiretroviral treatment, AZT Zidovudine, ABC Abacavir, EFV Efavirenz, 3TC Lamivudine, LPV/r Nevirapine, TDF Tenofovir, TDF Lopinavir boosted by Ritonavir, DTG Dolutegravir, ATV/r Atazanavir boosted with ritonavir, D4T Stavudine, DDI Didanosine
Others*: D4T/3TC/LPV/r (5), ABC/DDI/LPV/r (1), TDF/3TC/LPV/r (4), DDI/3TC/NVP (1)
Reasons for antiretroviral regimen modification
The mean number of ART regimen changes after initiation was 2 ± 1 per adolescent and involved 571 participants (95.3%). The primary reason for regimen modification was treatment optimization, accounting for 438 cases (73.1%), including 400 adolescents (66.8%) who transitioned to optimized antiretroviral regimens. Other reasons included treatment failure and adverse drug reactions related to zidovudine, efavirenz, and nevirapine (Fig. 2).
Fig. 2.
Reasons for therapeutic changes of HIV-infected adolescents. Legend. ART: Antiretroviral; others*: AZT-induced anemia, Efavirenz-related side effects, and Nevirapine-related side effects
Transition to optimized treatment regimens
At the time of inclusion, 391 adolescents were receiving optimized antiretroviral regimens, corresponding to a prevalence of 65.3%. The mean duration of exposure to optimized regimens was 11.7 ± 5.7 months, with a range of 1 to 29 months (Fig. 3).
Fig. 3.
Prevalence of HIV-infected adolescents on optimized treatment regimens
Among the 391 adolescents receiving Optimized Treatment Regimens, 366 (93.6%) had previously been on first-line ART, including 256 (69.9%) receiving TDF/3TC/EFV, while 25 (6.4%) had been on second-line regimens. The majority of Optimized treatment regimens consisted of fixed-dose combinations of tenofovir/lamivudine/dolutegravir (TLD), prescribed to 339 adolescents (86.7%). The ABC/3TC/DTG regimen was used in 37 adolescents (9.5%), while 15 adolescents (3.8%) received ABC/3TC/LPV/r.
Impact of optimized treatment regimens on nutritional and virological outcomes
Before optimization, 351 adolescents (89.8%) had normal nutritional status, 22 (5.6%) were overweight, and 18 (4.6%) had moderate malnutrition. After optimization, the proportion with moderate malnutrition decreased to 1.8% (7/391), while the proportion of overweight adolescents increased to 7.2% (28/391), the majority of whom were female (71.4%).
Mean body weight increased significantly from 43.2 ± 13.0 kg before optimization to 46.7 ± 13.3 kg after optimization (p < 0.001). Mean body mass index (BMI) increased from 18.8 ± 3.2 kg/m² to 19.6 ± 3.0 kg/m² (p < 0.001), while mean height remained stable. Optimized regimens were associated with a significant improvement in nutritional status among adolescents with moderate malnutrition (Table 3).
Table 3.
Anthropometric characteristics and nutritional status of HIV-infected adolescents before and after transition to optimized treatment regimens (n = 391)
| Variables | Before OTR | After OTR | p-value |
|---|---|---|---|
| Weight (kg), mean ± SD | 43.2 ± 13.0 | 46.7 ± 13.3 | < 0.001 |
| Height (m), mean ± SD | 1.50 ± 0.15 | 1.53 ± 0.14 | < 0.001 |
| BMI (kg/m²), mean ± SD | 18.8 ± 3.2 | 19.6 ± 3.0 | < 0.001 |
| BMI-for-age categories, n (%) | |||
| Normal weight | 351 (89.8) | 356 (91.0) | 0.534 |
| Overweight | 22 (5.6) | 28 (7.2) | 0.318 |
| Moderate malnutrition | 18 (4.6) | 7 (1.8) | 0.042 |
Legend. Values are presented as mean ± SD or n (%). BMI-for-age categories were determined according to WHO growth standards. Statistical significance was set at p < 0.05.
BMI Body Mass Index, OTR Optimized Treatment Regimens, SD Standard Deviation
Among the 391 adolescents receiving optimized regimens, 329 (84.1%) had achieved viral suppression (< 1,000 copies/ml) prior to regimen optimization, while 62 (15.9%) had unsuppressed viral loads. Among adolescents with unsuppressed viral loads before transition, 48 (77.4%) achieved viral suppression after switching to optimized regimens, whereas 14 (22.6%) remained unsuppressed.
Overall, following transition to optimized regimens, 370 adolescents (94.6%) achieved viral suppression. Adolescents receiving optimized regimens were significantly more likely to achieve viral suppression compared with the pre-optimization period (odds ratio [OR]: 3.3; 95% confidence interval [CI]: 2.0–5.6; p < 0.001). With regard to nutritional status, optimized regimens were associated with a significant reduction in moderate malnutrition (OR: 0.38; 95% CI: 0.16–0.91; p = 0.042) (Table 4).
Table 4.
Impact of the transition to optimized Treatment Regimens (OTR) on the management of HIA (n = 391)
| Variables | OTR | OR | 95% CI | p-value | |
|---|---|---|---|---|---|
| Before n (%) | After n (%) | ||||
| Viral load ( copies/ml) | |||||
| <1000 | 329 (84.1) | 370 (94.6) | 3.3 | [2.0-5.6] | < 0.001 |
| >1000 | 62 (15.9) | 21 (5.4) | 1 | — | — |
| Nutritional status of HIA, BMI-for-age categories, n (%) | |||||
| Normal | 351 (89.8) | 356 (91.0) | 1 | — | — |
| Overweight | 22 (5.6) | 28 (7.2) | 1.29 | [0.73–2.30] | 0.465 |
| Moderate malnutrition | 18 (4.6) | 7 (1.8) | 0.38 | [0.16–0.91] | 0.042 |
Legend. HIA HIV-infected Adolescents, OTR Optimized Treatment Regimens, OR Odds ratio, CI Confidence interval,
BMI-for-age categories were determined according to WHO growth standards. Statistical significance was set at p < 0.05
Discussion
At the end of our study, 599 HIV-infected adolescents were included, of whom 65.3% benefited from a transition to optimized treatment regimens. This proportion is consistent with recent reports from sub-Saharan Africa showing increasing access to dolutegravir (DTG)-based optimized regimens among adolescents [15–20]. More than half of the study population (52.1%) were female, with a median age of 15 years. The female predominance was consistent with findings reported by Fokam et al. in Cameroon in 2017 [21] and may be explained by global epidemiological trends indicating that adolescent girls remain disproportionately affected by HIV [1, 2]. However, the median age in previous studies ranged from 12 to 18 years due to broader population selection, including adolescents and young adults living with HIV [9, 19].
The majority of adolescents acquired HIV through vertical transmission, and nearly half were orphans, including 129 (21.5%) who were maternal orphans. These findings are consistent with previous reports from Cameroon [20]. Limited access to antiretroviral therapy within the framework of prevention of mother-to-child transmission (PMTCT) and delayed ART initiation policies before the adoption of universal treatment strategies may explain the high AIDS-related maternal mortality observed in earlier periods [22–25].
The median age at HIV diagnosis among adolescents in our study was lower than that reported in 2017 in Yaoundé, Cameroon [21]. This may reflect improvements in early diagnosis strategies, including active case-finding and increased access to HIV testing services in recent years.
Among the 599 HIA, 530 (88.5%) were initiated on first-line ART regimens consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) combined with one non-nucleoside reverse transcriptase inhibitor (NNRTI), while 50 (8.3%) received a first-line regimen combining two NRTIs with a ritonavir-boosted protease inhibitor.
These findings are consistent with WHO recommendations between 2010 and 2015 [22–24]. In our study, 202 out of 599 adolescents (33.7%) experienced at least one first-line treatment failure and were switched to second-line regimens combining two NRTIs with a ritonavir-boosted protease inhibitor, a proportion higher than the 24.7% reported by Fokam et al. in Yaoundé in 2017 [21]. This difference may be explained by limited availability of optimized regimens during earlier program phases and challenges related to adherence. Adolescents who transitioned to optimized treatment regimens were 3.3 times more likely to achieve viral load suppression, consistent with recent studies conducted in sub-Saharan Africa demonstrating significant improvements in virological outcomes following transition to DTG-based regimens [17–20, 25]. However, viral suppression may also depend on other factors such as adherence difficulties and psychosocial challenges common in this age group. Previous studies in Cameroon have shown that adolescents are particularly vulnerable to treatment failure, especially among orphans and those living in unstable family environments [26–29]. Recent evidence has further highlighted that stigma, mental health disorders, lack of social support, and transition challenges from pediatric to adult care significantly influence adherence and viral suppression outcomes among adolescents living with HIV [28–30]. These results underscore the importance of comprehensive, tailored, multidisciplinary, and continuous care programs for HIV-infected adolescents. Transition to DTG-based regimens was beneficial for adolescents with low body mass index (BMI) on efavirenz-based regimens, with an improvement in nutritional status after optimization. Before transition to OTR, 89.5% (350/391) of adolescents had normal nutritional status, 5.6% (22/391) were overweight, and 5.4% (19/391) had moderate malnutrition. These results were similar to those reported by Thivalapill et al. [31]. After transition, the proportion of adolescents with moderate malnutrition decreased to 2%, while the prevalence of overweight increased from 5.6% to 7.2%, particularly among females. These findings are consistent with emerging evidence suggesting that DTG-based regimens are associated with weight gain, especially in adolescent girls [20, 31, 32]. Beyond weight gain, DTG has been associated with other adverse drug reactions that warrant consideration. While DTG is generally well tolerated, studies have reported neuropsychiatric adverse events such as insomnia, headache, and anxiety, particularly among women and older patients [33, 34]. These findings highlight the importance of ongoing pharmacovigilance and long-term monitoring of DTG-related adverse events in adolescent populations. Among the 391 adolescents receiving optimized treatment regimens, 93.6% were on first-line ART before transition, similar to findings from sub-Saharan African cohorts [17–20], but higher than those reported in earlier programmatic settings [10]. Overall, 85.2% had viral loads below 1000 copies/ml before transition, increasing to 94.7% after transition. Similar trends were reported in clinical trials and cohort studies, including those by Turkova et al. [11] and the NAMSAL study conducted in Cameroon [35]. More recent studies also confirm high viral suppression rates following DTG transition in adolescents across African settings [17, 36]. However, our results were higher than those reported in some settings, likely due to the inclusion of clinically stable adolescents.
Conclusion
Transition to optimized antiretroviral regimens was associated with viral load suppression and weight gain among HIV infected adolescents with moderate malnutrition. Transition to DTG among viral load suppression adolescents was associated with an increased rate of BMI change, which was significantly higher among girls than boys.
Strengths of the study
This study has several major strengths. First, the multicenter design involving five healthcare facilities representing different levels of the healthcare system in Douala (secondary referral hospital, district hospitals, and district medical center) enhances the external validity and generalizability of the findings to similar programmatic settings. Second, the large sample size of 599 adolescents, well above the calculated minimum of 351, provided adequate statistical power for the analyses performed. Third, the study assessed both virological and nutritional outcomes, thus providing a comprehensive evaluation of the impact of optimized treatment regimens. Fourth, the study was conducted in a real-world clinical setting reflecting routine programmatic conditions rather than controlled trial environments, making the findings directly relevant to clinical practice and policy. Finally, this study represents one of the first assessments of the impact of ART optimization specifically among adolescents in Cameroon following the 2020 revision of the national recommendations for the management of HIV in children and adolescents, and provides valuable data to improve the scaling up of dolutegravir-based (DTG) treatment regimens in the country.
limitations of the study
This study has some limitations that should be considered when interpreting the results. The relatively short follow-up period after the transition may not fully capture long-term metabolic effects, such as obesity. A longitudinal study with extended follow-up would allow for a better assessment of the long-term effects of OTR on viral suppression and the nutritional status of these adolescents. Only clinically stable adolescents were eligible for the transition to optimized treatment regimens. Despite these limitations, our study provides important data on the impact of OTR in a real healthcare setting in sub-Saharan Africa and supports current WHO recommendations to optimize antiretroviral therapy in HIV infected adolescents.
Acknowledgements
We are deeply grateful to the adolescents who agreed to participate in this study, to the parents and guardians who provided consent for their children’s inclusion, and to all healthcare staff of the participating healthcare facilities for their support and cooperation during the investigation.
Abbreviations
- ART
Antiretroviral Therapy
- AIDS
Acquired Immune Deficiency Syndrome HIV: Human Immunodeficiency Virus
- HIA
HIV-infected adolescents
- ARV
Antiretroviral
- OTR
optimized Treatment regimens
- DLH
Douala Laquintinie hospital, NDH: New-Bell District hospital
- DDH
Déido District hospital
- BDH
Bonassama District hospital
- SDMC
Soboum District Medical Center
- AZT
Zidovudine
- ABC
Abacavir
- EFV
Efavirenz
- 3TC
Lamivudine
- NVP
Nevirapine
- TDF
Tenofovir
- LPV/r
Lopinavir boosted by Ritonavir
- DTG
Dolutegravir
- ATV/r
Atazanavir boosted with ritonavir
- D4T
Stavudine
- DDI
Didanosine
- NNRTI
Non-Nucleoside Reverse Transcriptase Inhibitors, NRTI: Nucleoside Reverse Transcriptase Inhibitors
- IQR
Interquartile range
- CI
Confidence Interval
- BMI
Body Mass Index
- OR
Odds Ratio
- VL
Viral load
- VS
Viral Suppression
- WHO
World Health Organization
Authors’ contributions
CIP, PEE, and GDN designed and wrote the protocol for this study. SJN did data collection. CIP and CEEM supervised the study. CIP, PEE, NP, JPM did data analysis for this study and wrote the draft manuscript. DMKK, SJN, DDN, FAN, SNP, MBR, ADD, AMD, CEE, HI, NP and CIP revised the manuscript for scientific input. All authors agreed to submit the current manuscript as the final version.
Funding
No funding was received for this study.
Data availability
The data that support the findings of this study are available on request from the corresponding author, CIP.
Declarations
Ethical approval and consent to participate
This study received approval from the Institutional Ethics Committee for Research on Human Health of the University of Douala (reference: (N° 2992 CEI-UDO / 06/2022 / T).) as well as administrative authorizations from the Regional Delegation of Public Health Littoral (N°0175/AAR/MINSANTE/DRSPL/BCASS) and the management of Laquintinie Hospital in Douala (N°012/AR/MINSANTE/DHL). Additionally, the research protocol was approved by the local ethics committees of each participating hospital. Prior to inclusion in the study, written informed consent was obtained from all parents or legal guardians of adolescents. For all adolescents, written assent was also obtained in addition to parental consent in accordance with national ethical guidelines before inclusion in the study. Participants were informed about the voluntary nature of their participation and their right to withdraw from the study at any time without prejudice to their clinical care. Confidentiality and anonymity of data were ensured in accordance with the Declaration of Helsinki.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author, CIP.