Acquired HIV-1 drug resistance to reverse transcriptase and protease inhibitors among people failing antiretroviral therapy in Cameroon and implications for future treatment options

Abstract

HIV-1 drug resistance (HIVDR) surveillance among individuals failing antiretroviral therapy (ART) is essential to selecting optimal ART-combinations for use in a public health approach in low-middle-income countries (LMICs) where routine HIVDR-testing remains limited. This study describes patterns of acquired drug resistance (ADR) and potentially active drugs for subsequent ART regimens in individuals failing treatment in Cameroon. We conducted a cross-sectional, laboratory-based sentinel study among ART-failing individuals from October 2022 through April 2023 at the “Chantal Biya” International Reference Centre, Yaoundé-Cameroon. Individual samples with confirmed virological failure were sequenced in HIV-1 protease and reverse-transcriptase genes using Sanger sequencing and analysed using Stanford HIVdatabase.v.9.4. Overall, 203 individuals were enrolled, median [IQR] age 37 [16-47] years with 58.1% (118/203) being female. Median [IQR] duration on ART was 10 [6.9–13.3] years, with majority failing second-line (78.7%; 160/203). HIVDR rate was 85.3% (29/34) and 88.1% (140/160) in those failing first-line and second-line therapy respectively (p = 0.7). NNRTI, NRTI and PI/r resistance in individuals failing first-line ART was 85.3% (9/34), 82.4% (28/34) and 2.9% (1/34) respectively. In second-line failure, NNRTI, NRTI and PI/r resistance was 86.8% (138/160), 84.9% (135/160) and 47.17% (75/160) respectively. NRTI-NNRTI dual-class-resistance was 82.4% (28/34) after first-line and 84.3% (134/160) after second-line (p = 0.842), while triple-class-resistance was 2.9% (1/34) after first-line and 45.3% (72/160) after second-line (p < 0.0001). After first-line, TDF and AZT maintained potential efficacy in respectively 53.4% (18/34) and 46.7% (16/34) of individuals, while 46.7% (16/34) had cross-resistance to second-generation NNRTI. After second-line failure, 95.6% (153/160) maintained DRV/r efficacy, as compared to 67.3% for ATV/r (p < 0.0002), 73.9% for LPV/r (p < 0.0002), and 34.7% (56/160) for RPV/DOR. Among ART-failing individuals in Cameroon, levels of ADR are high with significant levels of cross-resistance to second-generation NNRTI, hence potentially jeopardizing the use of long-acting cabotegravir/rilpivirine. Furthermore, HIVDR testing could be considered from first-line failure in such settings, but chiefly following second-line failure wherein triple-class-resistance is common and calls for novel antiretrovirals in similar LMICs.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12981-025-00775-z.

Background

The Human immunodeficiency virus (HIV) is still a global health problem, having claimed about 40.4 million lives in 2022 [1]. Globally, there were about 39 million people living with HIV (PWH) at the end of 2022, about two third (25.6 million) of whom were in Africa, the region most affected by pandemic [2]. Cameroon, a lower-middle-income country (LMIC) in Sub-Saharan Africa (SSA) also bears significant burden, with about 460,000 PWH at the end of 2022 [3].

Over the years, antiretroviral therapies (ARTs) which are combinations of antiretrovirals (ARVs) have been used in the management of PWH [4]. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets, globally in 2022, 86% of PWH were aware of their HIV status, 89% of these were on ART, among whom 93% achieved viral suppression [6]. In Cameroon, this target currently stands at 93-88-79 [3]. Since the implementation of the universal test and treat in Cameroon [7] the preferred first-line regimens have been two NRTIs and one NNRTI, though DTG-based regimens have been introduced since 2020 according to the recent World health organization (WHO) treatment guidelines [8, 9].

Despite progress and benefits of ART scale-up [4], HIV drug resistance (HIVDR) emergence remains a formidable threat to ART-success and 95-95-95 UNAIDS targets. HIVDR can be acquired (ADR) in individuals receiving ART; transmitted (TDR) following transmission of resistant viruses during infection; or pre-treatment (PDR) when detected in ART-naive individuals initiating ART for the first time, or in individuals with previous ARV drug exposure (such as for prevention of mother to child transmission or pre-exposure prophylaxis) initiating or reinitiating first-line ART (that is re-initiating first-line ART after a period of treatment interruption) [10].

In Cameroon high rates of acquired HIVDR (87.7%) have been previously observed in individuals with virological failure (VL ≥ 1000 copies/ml) [11–15]. Given limited availability of HIV genotypic resistance testing (GRT) for individual management of PWH, the availability of surveillance data on HIVDR is crucial. Hence, the continuous need for updates on HIVDR surveillance especially among individuals failing ART; as an essential strategy to selecting optimal ART combinations [10]. The WHO recommends two main approaches; either a more expensive clinical-based surveillance approach, or the more recent and less expensive laboratory-based approach, suitable for settings with a viral load coverage greater than 60% (current viral load coverage in Cameroon is 65%) [16, 17]. Furthermore, in this era of DTG (an integrase strand-transfer inhibitor (INSTI) with higher genetic barriers to resistance), surveillance of HIVDR to the accompanying drug classes is necessary to ensure selection of the most appropriate accompanying molecules or therapeutic options. This would in turn avoid the risk of DTG functional monotherapy in treated individuals and the risks of resistance emergence to DTG [10, 18–20]. In this study, we give an update of acquired HIVDR patterns in Cameroon and describe the potential impact on subsequent ART-regimens. We also show the implications of our findings, with respect to the need of more innovative antiretroviral drugs in similar LMIC with limited therapeutic options.

Methods

Study design and study population

A cross-sectional, laboratory-based sentinel study was conducted during the reporting period of March to April 2023 at the Chantal Biya International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé-Cameroon among ART-failing PWH. Participants were on documented ART for at least 12 months and experiencing virological failure (viral load ≥ 1000 copies/ml). Unamplified samples, sequences with poor quality or incomplete coverage were excluded. Minimal sample size was 166, calculated at 95% confidence interval, 5% margin of error and predicted ADR prevalence of 87.7% [11].

Enrolment procedure and data collection

Individuals received for GRT were consecutively enrolled at CIRCB, between January 2022 to April 2023. In Cameroon, GRT is recommended following confirmed virological failure to second-line ARTs (viral load ≥ 1000 copies/ml), in children experiencing failure under protease inhibitors (PI/r), adolescents with multiple treatment changes and clinical suspicion of HIVDR (that is high viral load despite adherence). Data collection was done using a pre-established form from patients’ files. Variables included socio-demographics, ART and immuno-virological history (viral load and CD4 count), WHO clinical stages, date of HIV-1 infection, starting date of ART and ART durations.

Genotypic resistance testing and sequence interpretation and analysis

GRT was performed in the pol gene (protease (PR) and reverse transcriptase (RT)) on the stored samples with plasma viral load ≥ 1000 copies/ml, using the previously validated inhouse protocol as described by Fokam et al. [21]. Sequences were assembled and edited using Recall v2.28 [22], interpreted using Stanford HIV drug resistance database (https://hivdb.stanford.edu/) version 8.5 and subtyping performed using rapid subtyping tools as previously described [23].

Technical definitions

According to national guidelines [24], first-line regimens are either INST + 2NRTI (preferentially TDF + 3TC + DTG) or NRTI + 2NRTI (alternative first-line). Second-line regimens are PI/r (ATV/r or LPV/r) plus optimized NRTI backbone while third-line include regimens containing either DTG and/or DRV/r and/or NRTI (usually selected based on a genotypic resistance test). Treatment failure is defined as two consecutive viral loads ≥ 1000 copies/ml following at least six months of antiretroviral therapy, with enhanced adherence counselling. Percentage of individuals with a genotypic susceptibility score (GSS) of < 30 on Stanford were considered to preserve potential efficacy while those with a GSS score of ≥ 30 were considered to have limited activity.

Data management and statistical analysis

Centre for disease control (CDC) Epi info version 7.2.6. was used for statistical analysis following data verification, cleaning and validation. The mean and standard deviation (SD) or median and inter-quartile range (IQR) were used for quantitative variables. Chi square/Fisher exact tests were used to compare categorical variables, while Student T test was used to compare continuous variables between groups. P values < 0.05 were considered statistically significant. Any variables with p values < 0.2 on bivariate analyses were eligible for multivariate analysis.

Results

Characteristics of study participants

Of 2109 individuals assessed, 203 met inclusion criteria, median age 37 [16-47] years and 118/203 (58.13%) females. The median [IQR] duration on ART was 10 [6.9–13.3] years, with majority (160, 78.70%) on second-line, 34 (16.80%) on first-line and 9 (4.50%) on third-line. Detailed regimens included: ABC + 3TC + EFV/NVP (0.98%); AZT + 3TC + EFV/NVP (1.47) TDF + 3TC + EFV/NVP (6.89%); TDF + 3TC + DTG (7.39%%); AZT + 3TC + DTG (0.49%); ABC + 3TC + DTG (3.94%); ABC + 3TC + ATV/r (17.73%); ABC + 3TC + LPV/r (6.40%); AZT + 3TC + ATV/r (15.76%), AZT + 3TC + LVP/r (5.42%); TDF + 3TC + ATV/r (29.56%); TDF + 3TC + LPV/r (3.94%). Overall, median [IQR] viral load was 46,000 [8,480 − 194,487] copies/ml and median [IQR] CD4 count was 239.50 [125–452] cells/µl. The median viral load was comparable after first (929,837 [7,309 − 132,270] copies/ml), second- (51,451 [9,632 − 204,463] copies/ml) and third-line failure (37,415 [8,930 − 369,430] copies/ml), p = 0.7. The median CD4 count was higher at first-line failure (406 [184–642] cells/µl) as compared to second-line failure (214.5 [103–394] cells/µl), p = 0.03, while there was limited CD4 data in those failing third-line. Table 1 shows characteristics of participants.

Table 1.

Summarized sociodemographic data of participants

Sociodemographic data	Frequency (n)	Percentage (%)
Age distribution in Years of participants
0–9	11	5.42
10–19	59	29.06
20–49	98	48.28
≥ 50	35	17.24
Sex
Female	118	58.13
Male	85	41.87
Zone of residence
Urban	148	72.91
Rural	55	27.09
Professiona
Health personnel	6	4.58
Lecturer	7	5.34
Student	44	33.59
Self-employed	49	37.40
Unemployed	6	4.58

^aInformation was available for 112 individuals

HIV genotypic and resistance profiles

HIVDR rates are summarized in Table 2. Overall HIVDR (presence of at least one HIVDR resistance mutation) was 87.19% (177/203). NRTI-NNRTI dual class resistance was similar in first- and second-line (p = 0.842), while triple-class resistance was higher in second-line as compared to first-line (p < 0.0001). The most prevalent viral clade was CRF02_AG (119 (58.60%)), followed by G (19 (9.36%)), A₁ (18 (8.87%), F2 (11(5.42%), D (8(3.94%), CRF01_AE (5(2.46%)), CRF18_cpx (5(2.46%), CRF06_cpx (3(1.48%), CRF11_cpx (3(1.48%), CRF22_01A1 (3(1.48%), CRF13_cpx (2(0.99%), CRF37_cpx (2(0.99%), H (1(0.49%) and G/D (1(0.49%) while three individuals (1.48%) harboured HIV-1 group O.

Table 2.

HIVDR prevalence

HIVDR	All participants, n (203)	AFLF (n = 34)	ASLF (n = 160)	ATLF (n = 9)
Overall, n (%)	177 (87.2)	29 (85.3)	141 (88.1)	7 (77.8)
NRTI, n (%)	171 (84.2)	28 (82.4)	136 (85.0)	7 (77.8)
NNRTI, n (%)	175 (86.2)	29 (85.3)	139 (86.9)	7 (77.8)
PI/r, n (%)	78 (38.4)	1 (2.9)	75 (47.2)	2 (22.2)
NRTI-NNRTI Dual class resistance, n (%)	170 (83.7)	28 (82.4)	135 (84.3)	7 (77.8)
NRTI-NNRTI-PI/r Triple class resistance, n (%)	75 (37.0)	1 (2.9)	72 (45.3)	2 (22.2)

HIVDR HIV drug resistance, AFLF After First-Line Failure, n Frequency, ASLF After Second-Line Failure, ATLF After Third-Line Failure

Mutational profiles

Mutational profiles are summarized in Fig. 1 (panel A, B and C). M184V mutation most prevalent among NRTI mutations (65.52%), followed by the thymidine analogue mutation (TAM), M41L (24.14%). Among NNRTI mutations, K103N was most prevalent (35.96%), followed by A98G (18.72%).

Fig. 1.

HIVDR mutational profile of participants. A describes the mutational profiles in the entire population (n = 203); B describes mutational profiles in individuals failing first-line antiretroviral therapy regimens (n = 34) and C describes mutational profiles in individuals failing second-line antiretroviral regimens (n = 160). N.B. Only major mutations according to the Stanford HIV Drug Resistance database were described. (https://hivdb.stanford.edu/)

Among PI/r mutations, M46I (19.70%), was most prevalent followed by F53L (12.81%).

Factors associated with HIVDR

Table 3 summarizes factors associated to HIV drug resistance (HIVDR). Neither age, gender, line of treatment, WHO clinical stage, viral load, CD4 count, nor genetic diversity were significantly associated with HIVDR (p > 0.05).

Table 3.

Factors associated with HIVDR

	HIVDR		OR	P value
	Present	Absent
Age distribution, n (%)
0–9	11 (100)	0 (0)		0.494
10–19	49 (83.05)	10 (16.95)
20–49	87 (88.78)	11 (11.22)
≥ 50	30 (85.71)	5 (14.29)
Gender, n (%)
Female	100 (84.75)	18 (15.25)	0.58	0.288 0.493
Male	77 (90.59)	8 (9.41)
Therapeutic line, n (%)
First-line	29 (85.29)	5 (14.71)
Second-line	140 (88.05)	19 (11.95)
Third-line	7 (77.78)	2 (22.22)
Clinical stage, n (%)
WHO stage I/II	69 (84.15)	13 (15.85)	0.61	0.555
WHO stage III/IV	26 (89.66)	3 (10.34)
Viral Load, median [IQR]	46 000	52 470	NA	0.745
CD4 count, median [IQR]	231	334	NA	0.290
CD4 count ranges
≤ 200 cells/µl	34 (89.47)	4 (10.53)	1.78	0.545
> 200 cells/µl	43 (82.69)	9 (17.31)
Genetic diversity, n (%)
CRF02_AG	105 (86.78)	16 (13.22)	0.91	1
Non-CRF02_AG	72 (87.80)	10 (12.2)
Pure	52 (86.67)	8 (13.33)	0.94	1
Recombinant	125 (87.41)	18 (12.59)

Viral load is in copies/ml while CD4 count in cells/mm³

HIVDR HIV drug resistance, OR Odds ratio

Potentially active drugs

Potentially active drugs after ART-failure are shown in Fig. 2 (Fig. 2A and B). Notably, after first-line failure, all PIs (DRV/r, ATV/r and LPV/r) had high efficacies (93.30%, 93.40% and 93.40% respectively), while among NRTI, TDF had the highest efficacy (53.40%), followed by AZT (46.70%). All first-generation NNRTI had low-levels of efficacy while second-generation NNRTI (DOR, RPV and ETR) had similar efficacies (53.30%). After second-line failure, DRV/r maintained high level potential efficacy (95.60%) as compared to ATV/r (67.30%, p < 0.0002) and LPV/r (73.90%, p < 0.0002). TDF potential efficacy was highest among NRTIs (67.20%), followed by AZT (54.40%), while ETR had the highest potential efficacy among NNRTIs (67.40%) with 65.20% efficacy for RPV.

Fig. 2.

Potentially active drugs after first-line treatment failure (A) and second-line treatment failure (B)

Participants on dolutegravir

Of the 24 DTG-exposed participants (13 (54.17%) female), median age was 17.4 [13.25–40.29] years with adolescents (0–19 years) most represented (14/24, 58.33%). Most (12/17 (70.59%)) where in a less advanced disease stage, with a median [IQR] viral load of 49,911 [5,728 − 345,595] copies/ml and median [IQR] CD4 count of 303 [184–584] cells/µl. Mean ART-duration was 8.93 ± 3.59 years, with a mean duration on DTG-ART of 1.2 ± 0.7 years. Majority were using DTG on first-line (15/24 (62.5%)), while 9 (37.5%) used it on third-line. Specifically, 15/24 (62.50%)) were on TDF + 3TC + DTG, 8(33.33%) on ABC + 3TC + DTG and 1 (4.17%) on AZT + 3TC + DTG.

Overall HIVDR in this group was 83.3% (20/24), with 79.2% (19/24) for NRTI resistance, 83.3% (20/24) for NNRTI resistance, and 8.3% (2/24) for PI/r resistance. NRTI-NNRTI dual class resistance was 79.2% (19/24) while 8.33% (2/24) had NRTI-NNRTI-PI/r triple class resistance. M184V (62.50%) was the most prevalent mutation. Supplementary figure Panel A summarizes the mutational profile in this group. All PI/r preserved potential efficacy in majority of individuals, with 95.8% (23/24) for ATV/r, 91.7% (22/24) for LPV/r and 100% (24/24) for DRV/r. As concerns NRTI, ABC preserved potential efficacy in 66.7% (16/24) of individuals, AZT in 55.3% (13/24) and TDF on 87.5% (21/24). Supplementary figure Panel B shows potentially active drugs that could accompany and/or substitute DTG and other INSTIs in patients failing DTG containing First-line and second-line regimens.

Discussion

We herein describe ADR patterns in ART-failing PWH in Cameroon. Although some data has previously been reported in this context, last reports were in the pre-DTG era, collected between 2011 and 2019 [14]. The current study gives an update on ADR, necessary to guide treatment options here and in similar RLS with limited laboratory capacity for GRT in ART-failing individuals [25]. Performed in the context DTG-roll-out, this update is of added relevance as it describes optimal accompanying regimens in DTG-failing failing individuals initially naïve to INSTI, increasing our chances for sustainability of DTG-based regimens. Lastly, given the continuous need for novel drugs in this context (such as second generation NNRTI, capsid inhibitors, nucleoside reverse transcriptase translocation inhibitors), our findings could help inform strategies around selecting eligible candidates for these therapies.

The overall high rate of HIVDR observed herein underscores its role as a major cause of virological failure, aligning with previous findings in similar populations [11]. HIVDR in this context is driven by limited treatment options, low genetic barrier regimens, poor adherence, inadequate viral load monitoring and delayed detection of treatment failure and resistance [26]. Indeed duration of treatment was long in this population (often associated to higher rates of HIVDR) [11], with poor immunovirological status, especially after second line failure, suggesting higher disease progression [26]. Proper monitoring strategies for viral load, CD4 count and GRT in this setting would enable timely detection of failure, reducing the risks of HIVDR accumulation and disease progression [27].

HIVDR rates were highest for NNRTIs, followed by NRTI and lastly PI/r [27]. Also, high rates of NNRTI and NRTI resistance were observed as from first-line failure, again calling for adequate monitoring to enable timely detection of failure, and potential benefits for GRT even as from first-line failure [26], though some studies suggest limited benefits of GRT in first-line failures [28]. Nonetheless, this could help preserve NRTI accompanying molecules used in first-line for use in subsequent ART-regimens [29]. The high NNRTI resistance supports progressive phase out of first-generation NNRTI, in favour of newer high genetic barrier ARV such as DTG-based regimens which have been excellent since implementation [30], supporting the necessity to strengthen this transition across all eligible populations (even in children and adolescents). Indeed, HIV-related morbidity and mortality remains worrying in paediatrics in this setting. In this study, all children aged 0–9 years and 83.1% of children aged 10–19 harboured a virus with at least one HIVDR mutation. Children and adolescents face additional challenges linked to social/psychological, drug dosing and formulations, poorer adherence, risks of TDR and PDR (especially to first generation NNRTI) and high viral loads at diagnosis and failure, which may all increase risks of HIVDR at failure, necessitating adapted strategies for optimal treatment outcomes [31–33]. Lastly, about 37.0% of our population had NRTI-NNRTI-PI/r triple-class resistance, raising the need for introduction of novel drug regimens with different mechanisms of action.

With respect to mutational profiles, the M184V mutation was most prevalent. Though this causes high resistance to 3TC/FTC, it potentializes AZT and TDF, while reducing viral replicative fitness. For this reason, 3TC/FTC are usually maintained in ART regimens despite M184V, which also serves as an adherence marker [34–37]. Both type I and II TAMs were present, causing varying levels of cross-resistance to ABC and TDF (higher in the case of type I TAMs), with potential to jeopardize ART-regimens even in individuals without previous exposure to ABC/TDF [38]. This leaves the possibility for suboptimal second-line-ART, with blind use of ABC/TDF, as poor documentation of treatment histories/records and medical nomadism are frequent in this context. GRT use may be of importance in such cases to identify unpredicted resistance/cross-resistance. The K103N mutation was most frequent among NNRTIs, confirming limited potential for recycling first generation NNRTIs [39]. Meanwhile, mutations causing cross-resistance to second generation NNRTI (Y181C, K101E/P, G190A, Y188L, M230L, and V106A) were frequent, with only about 50% of individuals preserving potential efficacy each to DOR, ETR or RPV after first-line, calling for careful considerations around the potential use of second-generation NNRTI (such as in acting and dual-ART regimens) [40]. This should take into account extensive exposure to first-generation NNRTI, high rates of NNRTI resistance in ART-failing individuals, and therefore the potential of archived NNRTI resistance in viral reservoirs, with potential to affect such therapeutic options [41–43]. Overall, PI/r resistance was lowest, supporting their use in second and third line (DRV/r) regimens [44], with the possibility of recycling ATV/r and LPV/r even after second line failure if helped by resistance testing.

The main limitation of this study was the inability to sequence of the integrase region in individuals on DTG-based regimens at the time of the study. It is worth noting that INSTI were introduced into Cameroonian guidelines (in first- or third-line regimens) only as from 2020 [24]. Therefore, GRT only involved the RT and PR regions, till recently when we developed a sequencing protocol for integrase sequencing [45], which was however not readily available yet for routine management at this time. Nonetheless, it is worth noting that integrase HIVDR remains rare in real world practice, occurring usually in some high-risk clinical scenarios, such as previous exposure to INSTI (which is not the case in this setting), use of DTG as mono or dual therapy, concomitant treatment with rifampicin or presence of resistance to NRTI accompanying molecules [46]. The few individuals on INSTI-based regimens here (24 out of 203) were at low risk of developing INSTI resistance. Furthermore, based on our studies carried out around the same period, there was high baseline efficacy of DTG, and little effect of DRMs on treatment response [5, 21, 31]. Indeed, of the 24 individuals, 15 were using DTG as first-line regimens, a population in which INSTI resistance is rare [32, 48]. To add, the median duration on DTG-based regimens was low (about one year) and resistance to NRTI and PI/r accompanying molecules in these individuals was also low (supplementary figure Panel A), suggesting preserved efficacies of DTG, favoured by its high genetic barrier and forgiveness to non-observance. To add, no individual had the K65R mutation (even though 23/24 of them used either ABC/3TC or TDF/3TC as accompanying molecules), again suggesting preserved efficacy of DTG. The unsuppressed viral loads in these individuals would therefore have been driven mainly by poor adherence to therapy. Lastly, recent findings have shown high rates of efficacy of DTG based regimens, even despite presence of resistance to accompanying NRTI molecules, although more data in clinical contexts is needed with respect to this [47, 49]. Another limitation is the use of conventional sanger sequencing, which limited our ability to detect minority viral populations, which have recently shown clinical relevance. Lastly, in the public health approach, the threshold for virological failure and eligibility for resistance testing was a viral load ≥ 1000 copies/ml making it possible for some resistance cases below 1000 copies/ml being missed [5]. Nonetheless, our study aligns with the current standard of care in this context and similar settings.

Conclusion

In this population with long duration on ART, poor immune-virological status and late detection of failure, ADR levels are high, and driven mostly by NNRTI resistance, supporting the use of NNRTI-sparing ART and careful considerations around the introduction of second generation NNRTI. All PI/r appear suitable for switch to second line while DRV/r remains active for switching to third-line ART, though some patterns after second line failure are complex, including triple-class resistance. Our findings underline the necessity for improved access to viral load and CD4 monitoring to enable opportune detection of failure, improved access and use of genotypic resistance testing (including newer drug targets such as integrase) to enable sustainable ART, and the need for introduction of new ARV drugs with novel mechanisms of action. These measures would significantly contribute to eliminating the HIV/AIDS pandemic by 2030.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary File 1—Supplementary Figure 1 Panel A: HIVDR mutational profile of participants on DTG. This describes the mutational profiles in the entire population with exposure to DTG (n=24). N.B. Only major mutations according to the Stanford HIV Drug Resistance database were described.( https://hivdb.stanford.edu/). Panel B: Potentially active antiretrovirals after treatment failure in participants on DTG.

Author contributions

Conceptualization, JF; methodology, JF, TTA, CAC.; software, CAC, ENJS, OEGBA, TTA; validation, JF, BTP and CAC; Laboratory analyses, OEGBA, SD, TTA; investigation, TAT; data curation and analysis, CAC, TTA; original draft preparation, TT, CC; review and editing, ACK, ENJS, OEGBA, ANN, SD, NE, EM, RA, AZB; resources, AN; supervision, VC, CP, GH, NN, AN. All authors have read and agreed to the published version of the manuscript.”

Funding

This study was funded by the Chantal BIYA International Reference Centre (CIRCB).

Data availability

The authors of this manuscript confirm that the data supporting the findings and conclusions of this study are available on request from the corresponding authors. The data are not publicly available due to their containing information that could compromise the privacy of research participants. However, sequences have been submitted to Genebank with available accession numbers provided (PQ893197, PQ893192, OQ985810, OR259747 and PQ893191) in the current version of the manuscript while the rest will be completed when made available by Genbank (submission ID: 2961867) (lines 451 to 455).

Declarations

Ethical approval

Ethical clearance was obtained from the University of Buea, Faculty of Health Sciences (FHS) Institutional Review Board (Ref. N° 2023/1945-01/UB/SG/IRB/FHS), administrative authorization obtained from the Director of CIRCB (Ref. N° 2112/016L/CIRCB/DIR/CL). A certified module on research ethics, the Training and Resources in Research Ethics Evaluation (TRREE-) was completed. The study was conducted according to the ethical principles outlined in the Declaration of Helsinki. Consent was waived as the research was carried out on stored samples.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.