Abstract
Introduction
Antiretroviral therapy (ART) reduces morbidity and mortality due to human immunodeficiency virus (HIV) infection. In 2019, Tanzania adopted Dolutegravir (DTG) as a first-, second-line, and third-line treatment for children and adolescents living with HIV (CALHIV). Viral load suppression (VLS) is desirable in the prevention of HIV transmission thus achieving the third ‘95’ target. DTG treatment has highly potent antiviral activity, a high genetic barrier to resistance, and a high safety profile. We aimed to determine VLS and associated factors among CALHIV on DTG-based ART in Tanzania.
Methods
We conducted a retrospective cohort analysis among CALHIV who were on a DTG-based regimen in Tanzania between 2019 and 2021. We extracted demographic and clinical characteristics from the care and treatment clinic database. A multilevel mixed effects Poisson regression model was used to determine factors associated with VLS at < 1000 copies/ml among CALHIV on a DTG-based regimen.
Results
A total of 63,453 CALHIV on a DTG-based regimen were analysed. The proportion of viral suppression was 91.64%. Overall, 66.19% of previously unsuppressed individuals became suppressed, and 88.45% of previously suppressed remained suppressed. Factors leading to higher chances of viral suppression were aged 15–19 years (aRR: 1.02; 95%CI: 1.017–1.03), those in WHO stage I (aRR: 1.03; 95%CI: 1.01–1.04), those in WHO stage II (aRR: 1.02; 95%CI: 1.00-1.04), and those who ever received a multi-month prescription on ART (aRR: 1.25; 95% CI: 1.23–1.28), while those aged 10–14 years (aRR: 0.98; 95%CI: 0.97–0.99), previously unsuppressed prior to starting DTG (aRR: 0.92; 95%CI: 0.91–0.93), duration on ART more than 24 months (aRR: 0.96; 95%CI: 0.94–0.97), not retained in care (aRR: 0.83; 95% CI: 0.77–0.89), severe malnutrition (aRR:0.77; 95%CI: 0.69–0.94) and coastal zone (aRR: 0.98; 95% CI: 0.96–0.99) were less likely to achieve VLS.
Conclusions
This study showed DTG-based regimens have a good response for both naïve, previously unsuppressed, and suppressed Children and Adolescents Living with HIV (CALHIV) with significant improvement in viral suppression. Improving retention in care and malnutrition might improve VLS and achieve the third ‘95’.
Keywords: Dolutegravir, HIV/AIDS, Viral load suppression, Children and adolescents
Introduction
HIV/AIDS is one of the greatest public health challenges in the world, whereby sub-Saharan Africa remains the region most heavily affected in the world. An estimated 1.8 (1.2–2.2) million children aged 0–14 were living with HIV at the end of 2020, and 150,000 children were newly infected. An estimated 100,000 children died of AIDS-related illnesses [1].
In Tanzania, it is estimated that around 68,000 (55,000–76,000) children aged 0–14 years and 1.7 (1.6–1.9) million adults were living with HIV/AIDS in 2023 [2]. From the Tanzania 2020 estimates, there were 6,500 new infections among children aged less than 15 years, and 78% of children living with HIV are on ART [2]. The prevalence of HIV according to the Tanzania HIV Impact Survey (THIS) of 2016/2017 was less than 2% among 15–19 year olds for both males and females and increases with age for both sexes. HIV care and treatment programs have scaled up rapidly in many countries in sub-Saharan Africa in recent years. The National AIDS Control Programme (NACP) in Tanzania has been coordinating the scale-up of quality HIV care and treatment services at all health facility levels: including public and private hospitals and in health centres and dispensaries throughout the country, whereby 6,206 (2103 CTCs & 4103 Option B+) health facilities started to provide care and treatment by December 2018 [3].
Major improvements in access to treatment have been greater for adults than for children due to the fundamental challenge in the development and approval of paediatric dosing and formulations for age and weight-specific thresholds for children and adolescents lagging for years and children did not benefit compared to adults despite the same level of engagement in terms of ART uptake [4].
Dolutegravir (DTG) is an Integrase Strand Transfer Inhibitor (INSTI) used as a first-line, second-line, and third-line HIV treatment regimen. According to the World Health Organization (WHO) updated antiretroviral therapy guidelines of 2018, DTG is recommended at ≥ 6 years of age or weight ≥ 20 kg, and children weight for age below < 20 kg use Lopinavir/ritonavir with or without being exposed to the Nevirapine among exposed infants from the risk mothers. Tanzania adopted DTG in 2019 among children and adolescents weighing ≥ 20 kg. Hence, there is a need to study treatment outcomes of DTG-based ART regimens due to their potent antiviral activity in reducing HIV incidence by promoting rapid viral suppression, a high genetic barrier to resistance, and a better safety profile [5]. Yet, in our setting, the prediction of viral suppression and associated factors has not been validated. Thus, there is still little support for the use of DTG-based regimens in mass treatment programs. Hence, there is a need to assess viral suppression among children and adolescents who are on these new antiretroviral drugs. This is because a single study on DTG has shown adolescents born in Sub-Saharan countries were more likely to have virological failure compared to those born in other countries [6].
Methods
Study design and setting
This was a retrospective cohort analysis among children and adolescents living with HIV (CALHIV) who were on an ART-initiated DTG-based regimen in Tanzania Mainland between January 2019 and December 2021. The study utilized de-identified, routinely collected data from Tanzania Care and Treatment Centres (CTC).
Study population and period
The analysis includes CALHIV on a DTG-based regimen, aged between 1 and 19 years at the time of ART initiation and enrolled in CTCs from January 2019 to December 2021. CALHIV with less than six months on ART and missing any viral load results after initiation of DTG were excluded from the analysis.
Data sources, longitudinal record linkage, and study variables
This study utilized data from HIV-positive children and adolescent clients who were on DTG from January 2019 to December 2021. We obtained data from routinely collected data of the care and treatment clinics (CTC) for HIV-positive clients in Tanzania. We only included health facilities who initiated DTG-based regimens. The data set originates from the National Aids Control Programme (NACP).
We linked data from multiple sources using unique patient CTC ID, the pharmacy module record number of drugs dispensed at each clinic visits, viral load results from the laboratory and demographic information in patient files during each clinic visit.
We defined the dependent variable, HIV viral suppression, as having a last plasma viral load of less than < 1000 copies/ml, which we named “Yes” 1, and having a plasma viral load of equal to or greater than 1000 copies/ml we named “No” 0.
Independent variables were included based on the available data; age categories in years (1–4, 5–9, 10–14 or 15–19), sex (male or female), baseline WHO clinical stages (Stage I, II, III and IV), baseline CD4 cell count (< 200, 200–350 and > 350), BMI categorized as underweight (< 18.5 kg/m2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2) and obese (≥ 30 kg/m2) for CALHIV aged ≥ 9 years with documented information on weight and height, prior DTG status (Experienced suppressed, experienced unsuppressed and Naive), duration on ART (6–12 months, 13–24 months and > 24 months), ever received Multi Month Subscription (Yes and No), history of TB treatment (Yes and No), retention in care (In care, lost-to-follow up, transferred and died) and geographical zones (central, lake, western, northern, coastal and southern highland).
Data analysis
A cleaned dataset was analysed using STATA version 15.0 (Stata Corp, College Station, USA). Descriptive statistics were summarised using means, standard deviation (SD), and median (IQR) for continuous variables whereas frequency and proportion were used for categorical variables. A proportion of HIV VLS was calculated as the number of CALHIV with < 1000 copies/ml divided by the total number study participants. A Chi-square test was used to compare the difference in VLS across CALHIV characteristics. Finally, a multilevel mixed effects Poisson regression model function with a robust estimator was to determine the factors associated with HIV viral suppression on a DTG-based regimen. Magnitude and strength of association were presented using Relative Risk (RR) and its 95% Confidence Interval (CI). We included variables into a multivariable regression model based on statistical significance and clinical relevance. Statistical significance was set at p < 0.05.
Results
Sample size estimation
A total of 230,310 CALHIV were enrolled between January 2019 and December 2021. Among them, 96,648 (41.96%) of CALHIV were on a DTG-based regimen and 133,662 (58.04%) were on NNRTI and PI. The DTG cohort consisted of 17,925 (18.56%) CALHIV were new on DTG (Naive), 52,275 (54.07%) were switched from an NNRTI, and 26,448 (27.37%) were switched from a PI regimen. A total of 33,195 (33.01%) individuals on DTG were excluded from the analysis as they did not meet eligibility criteria. The final sample was 63,453 as shown in the flow diagram (Fig. 1).
Fig. 1.
Flow chart showing the recruitment of the study population
Socio-demographic and clinical characteristics among the CALHIV
Our findings showed that more than one-third (34.4%) of CALHIV were aged 1–4 years, and their mean age was 7.74 (± 5.37) years at baseline. Most study participants 56.9% were females. At baseline (when CALHIV initiated on ART), many of the study participants experienced suppression with 63.4% prior to starting DTG, 23.9% experiencing unsuppressed prior to starting DTG, and 12.7% were naïve prior to starting DTG. Of most of the study participants, 84.3% had more than 24 months of duration on antiretroviral therapy. With reference to study participants, 42.7% were attending a hospital facility type, 76.1% were attending a public facility, and 27.2% were living in the lake zone (Table 1).
Table 1.
Socio-demographic and clinical characteristics among children and adolescents living with HIV in Tanzania (CALHIV) (N = 63,453)
| Characteristics | Frequency | Percentage |
|---|---|---|
| Sex | ||
| Male | 27,345 | 43.1 |
| Female | 36,108 | 56.9 |
| Baseline age (years) | ||
| 1–4 | 21,852 | 34.4 |
| 5–9 | 20,009 | 31.5 |
| 10–14 | 11,707 | 18.5 |
| 15–19 | 9,885 | 15.6 |
| Mean (± SD) | 7.74 (5.37) | |
| Base WHO clinical staging | ||
| Stage I | 26,026 | 41.0 |
| Stage II | 18,026 | 29.5 |
| Stage III | 16,112 | 25.4 |
| Stage IV | 2,565 | 4.0 |
| Baseline CD4 cells/mm3 (n = 35,478) | ||
| < 200 | 3,101 | 8.7 |
| 200–349 | 1,905 | 5.4 |
| >=350 | 30,472 | 85.9 |
| Median (IQR) | 427 (162–742) | |
| Baseline BMI (Kg/M2) (n = 23,687) | ||
| Underweight | 18,478 | 78.0 |
| Normal | 3,312 | 13.9 |
| Overweight | 510 | 2.2 |
| Obesity | 1,387 | 5.9 |
| Median (IQR) | 15.6 (13.9–17.9) | |
| Prior DTG status (n = 54,531) | ||
| Experienced suppressed | 34,557 | 63.4 |
| Experienced unsuppressed | 13,041 | 23.9 |
| Naive | 6,933 | 12.7 |
| Duration on ART | ||
| 6–12 months | 3,833 | 6.0 |
| 13–24 months | 6,108 | 9.6 |
| > 24 months | 53,512 | 84.3 |
| DTG regimen (n = 63,303) | ||
| TDF + 3TC + DTG (TLD) | 38,645 | 61.0 |
| ABC + 3TC + DTG | 22,578 | 35.7 |
| AZT + 3TC + DTG | 2,080 | 3.3 |
| Ever received MMS | ||
| No | 7,476 | 11.8 |
| Yes | 55,977 | 88.2 |
| Child exposed to PMTCT | ||
| No | 58,217 | 91.7 |
| Yes | 5,236 | 8.3 |
| History of TB treatment | ||
| No | 57,592 | 90.8 |
| Yes | 5,861 | 9.2 |
| Current malnutrition status (n = 56,083) | ||
| No malnutrition | 55,601 | 99.1 |
| Mild & moderate | 450 | 0.8 |
| Severe | 32 | 0.1 |
| Regimen | ||
| First line | 56,870 | 89.6 |
| Second line | 6,583 | 10.4 |
| Retention in care | ||
| In care | 63,047 | 99.4 |
| Lost to follow up | 24 | 0.1 |
| Transferred | 65 | 0.1 |
| Died | 317 | 0.4 |
| Facility type (n = 63,136) | ||
| Dispensary | 15,494 | 24.5 |
| Health centre | 20,665 | 32.7 |
| Hospital | 26,977 | 42.7 |
| Facility ownership (n = 63,136) | ||
| Private/FBO | 15,066 | 23.9 |
| Public | 48,070 | 76.1 |
| Zone (n = 63,136) | ||
| Central zone | 6,510 | 10.3 |
| Coastal zone | 13,400 | 21.2 |
| Lake zone | 17,152 | 27.2 |
| Northern zone | 7,536 | 11.9 |
| Southern highland | 16,907 | 26.8 |
| Western zone | 1,631 | 2.6 |
Frequency (n) do not tally to the total due to missing values
MMS multi-month subscription; PMTCT prevention of mother to child transmission; TB tuberculosis; BMI body mass index; CD4 cluster of differentiation 4; ART antiretroviral therapy; FBO Faith based organizations; DTG dolutegravir; TDF tenofovir; 3TC lamivudine; ABC abacavir; AZT azidothymidine (Zidovudine); ART antiretroviral therapy
Proportion of HIV viral suppression among children and adolescents on dolutegravir (DTG) based ART
Among CALHIV on a DTG-based regimen with pre- and post-viral load tests, 88.4% of those who were suppressed before DTG, remained suppressed. Of those who were unsuppressed before DTG, 66.1% became suppressed. After six months on DTG, among naïve patients on a DTG-based regimen, 91.7% achieved viral suppression as shown in Fig. 2.
Fig. 2.
Viral Suppression at baseline, after 6 months among Naïve and last viral load among CALHIV on DTG-based regimen (N = 54,531)
Additionally, the proportion of CALHIV on a DTG-based regimen who achieved viral suppression was higher in ART naïve (93.2%) than in treatment-experienced CALHIV with (91.4%) p-value < 0.001, as shown in Fig. 3.
Fig. 3.
Viral Load among treatment naïve and experienced CALHIV on DTG-based regimen (N = 63,453)
Among the 63,453 CALHIV on DTG, the prevalence of viral suppression was 91.64% (95%CI: 91.42–91.85; N = 58,147). The proportion of viral suppression among females was significantly higher with 92.04% (95%CI: 91.76,92.32), compared to viral suppression among males with 91.10% (95%CI: 90.76,91.43).
Among those with pre- and post-DTG VL, 94.28% (95%CI: 94.04,94.52; P-value:<0.001) of previously suppressed participants remained suppressed, 84.85% (95%CI: 84.22,85.45; P-value:<0.001) of previously unsuppressed became virally suppressed, and 93.21% (95%CI: 92.59,93.78; P-value:<0.001) of treatment-naïve participants who started DTG became virally suppressed. Among CALHIV on a DTG-based regimen with 24 months or less duration on ART, had a significantly higher proportion of viral suppression with 92.72% (95%CI: 92.19,93.21; P-value:<0.001) compared to individuals with a duration of more than two years (12 months) on ART with 91.44% (95% CI: 91.20,91.67; P-value:<0.001). More results are shown in Table 2.
Table 2.
Proportion of HIV viral suppression by socio-demographic and clinical characteristics of the CALHIV on DTG-based ART (N = 63,453)
| Variables | Viral Load | P-value | ||
|---|---|---|---|---|
| Unsuppressed n (%) 5,306 (8.36%) |
Suppressed (< 1000 copies/ml) | |||
|
n (%) 58,147 (91.64%) |
95% CI 91.42,91.85 |
|||
| Sex | ||||
| Male | 2,433 (8.90) | 24,912 (91.10) | 90.76,91.43 | < 0.001 |
| Female | 2,873 (7.96) | 33,235 (92.04) | 91.76,92.32 | |
| Age group (years) | ||||
| 1–4 | 1,684 (7.71) | 20,168 (92.29) | 91.93,92.64 | < 0.001 |
| 5–9 | 1,810 (9.05) | 18,199 (90.95) | 90.55,91.34 | |
| 10–14 | 1,123 (9.59) | 10,584 (90.41) | 89.86,90.93 | |
| 15–19 | 689 (6.97) | 9,196 (93.03) | 92.51,93.52 | |
| WHO staging | ||||
| Stage I | 2,015 (7.74) | 24,011 (92.26) | 91.93,92.58 | < 0.001 |
| Stage II | 1,585 (8.46) | 17,156 (91.54) | 91.14,91.93 | |
| Stage III | 1,449 (8.99) | 14,663 (91.01) | 90.56,91.44 | |
| Stage IV | 254 (9.90) | 2,311 (90.10) | 88.88,91.20 | |
| CD4 (cells/mm3) | ||||
| < 200 | 298 (9.61) | 2,803 (90.39) | 89.30,91.38 | 0.008 |
| 200–349 | 175 (9.19) | 1,730 (90.81) | 89.43,92.03 | |
| >=350 | 2,487 (8.16) | 27,985 (91.84) | 91.53,92.03 | |
| BMI (Kg/M2) | ||||
| Underweight | 1,610 (8.71) | 16,868 (91.29) | 90.87,91.69 | 0.512 |
| Normal | 262 (7.91) | 3,050 (92.09) | 91.12,92.96 | |
| Overweight | 44 (8.63) | 466 (91.37) | 88.60,93.52 | |
| Obesity | 119 (8.58) | 1,268 (91.42) | 89.83,92.78 | |
| Prior DTG status | ||||
| Experienced suppressed | 1,975 (5.72) | 32,582 (94.28) | 94.04,94.52 | < 0.001 |
| Experienced unsuppressed | 1,976 (15.15) | 11,065 (84.85) | 84.22,85.45 | |
| Naive | 471 (6.79) | 6,462 (93.21) | 92.59,93.78 | |
| Duration on ART | ||||
| 24 months or less | 724 (7.28) | 9,217 (92.72) | 92.19,93.21 | < 0.001 |
| > 24 months | 4,582 (8.56) | 48,930 (91.44) | 91.20,91.67 | |
| Current DTG regimen | ||||
| Other DTG regimen | 109 (7.31) | 1,383 (92.69) | 91.26,93.81 | 0.382 |
| TDF + 3TC + DTG (TLD) | 389 (6.67) | 5,445 (93.33) | 92.66,93.94 | |
| Ever received MMS | ||||
| No | 1,785 (23.88) | 5,691 (76.12) | 75.14,77.08 | < 0.001 |
| Yes | 3,521 (6.29) | 52,456 (93.71) | 93.51,93.91 | |
| Child exposed to PMTCT | ||||
| No | 4,896 (8.41) | 53,321 (91.59) | 91.36,91.81 | 0.147 |
| Yes | 410 (7.83) | 4,826 (92.17) | 91.41,92.87 | |
| History of TB treatment | ||||
| No | 4,749 (8.25) | 952,843 (91.75) | 91.53,91.98 | 0.001 |
| Yes | 557 (9.50) | 5,304 (90.50) | 89.72,91.22 | |
| Malnutrition status | ||||
| No malnutrition | 4,671 (8.40) | 50,930 (91.60) | 91.37,91.83 | < 0.001 |
| Mild & moderate | 49 (10.89) | 401 (89.11) | 85.88,91.68 | |
| Severe | 10 (31.25) | 22 (68.75) | 50.72,82.46 | |
| Retention in care | ||||
| Retained | 5,183 (8.22) | 57,864 (91.78) | 91.56,91.99 | < 0.001 |
| Not retained | 123 (30.30) | 283 (69.70) | 65.05,73.99 | |
| Facility type | ||||
| Dispensary | 1,365 (8.81) | 14,129 (91.19) | 90.73,91.63 | 0.021 |
| Health centre | 1,751 (8.47) | 18,914 (91.53) | 91.14,91.90 | |
| Hospital | 2,172 (8.05) | 24,805 (91.95) | 91.62,92.27 | |
| Facility ownership | ||||
| Private/FBO | 1,227 (8.14) | 13,839 (91.86) | 91.41,92.28 | 0.240 |
| Public | 4,061 (8.45) | 44,009 (91.55) | 91.30,91.79 | |
| Zone | ||||
| Central zone | 502 (7.71) | 6,008 (92.29) | 91.62,92.91 | < 0.001 |
| Coastal zone | 1,352 (10.09) | 12,048 (89.91) | 89.39,90.41 | |
| Lake zone | 1,023 (5.96) | 16,129 (94.04) | 93.67,94.38 | |
| Northern zone | 657 (8.72) | 6,879 (91.28) | 90.62,91.90 | |
| Southern highland | 1,618 (9.57) | 15,289 (90.43) | 89.98,90.86 | |
| Western zone | 136 (8.34) | 1,495 (91.66) | 90.22,92.91 | |
Key: Data are presented as n (row%)
CI confidence Interval; n frequency; %, percentage; DTG dolutegravir; TDF tenofovir; 3TC lamivudine; ABC abacavir; AZT azidothymidine (Zidovudine); MMS multi-month subscription; FBO faith-based organizations; ART antiretroviral therapy
*Chi-squared P-value
Factors associated with viral suppression among CALHIV on DTG-based ART
In an Unadjusted analysis, accounting for clustering at the health facility level, indicated that females were 1% more likely to achieve viral suppression compared to males (cRR: 1.01; 95% CI: 1.01–1.02). CALHIV who had ever received a multi-month subscription were 23% more likely to achieve viral suppression (cRR: 1.23; 95% CI: 1.23–1.25) compared to their counterparts (Table 3).
Table 3.
Factors associated with viral suppression among CALHIV on DTG-based ART adjusting for clustering effect (N = 63,453)
| Variable | Crude analysis | Adjusted analysis | ||
|---|---|---|---|---|
| RR (95%CI) | P-value | RR (95% CI) | P-value | |
| Sex | ||||
| Male | 1.00 | 1.00 | ||
| Female | 1.01 (1.01–1.02) | < 0.001 | 1.01 (0.99–1.01) | 0.095 |
| Age (years) | ||||
| 1–4 | 1.00 | 1.00 | ||
| 5–9 | 0.98 (0.98–0.99) | < 0.001 | 0.99 (0.98–0.99) | < 0.001 |
| 10–14 | 0.98 (0.97–0.99) | < 0.001 | 0.98 (0.97–0.99) | < 0.001 |
| 15–19 | 1.01 (1.00-1.02) | 0.021 | 1.02 (1.01–1.03) | 0.001 |
| WHO clinical | ||||
| Stage I | 1.02 (1.01–1.04) | < 0.001 | 1.03 (1.01–1.04) | 0.003 |
| Stage II | 1.02 (1.00-1.03) | 0.016 | 1.02 (1.00-1.04) | 0.015 |
| Stage III | 1.01 (0.99–1.02) | 0.118 | 1.02 (0.99–1.03) | 0.062 |
| Stage IV | 1.00 | 1.00 | ||
| CD4 cells/mm3 | ||||
| < 200 | 1.00 | |||
| 200–349 | 1.01 (0.99–1.03) | 0.622 | ||
| >=350 | 1.02 (1.00-1.03) | 0.008 | ||
| BMI (Kg/M2) | ||||
| Underweight | 1.00 | |||
| Normal | 1.01 (0.99–1.01) | 0.128 | ||
| Overweight | 1.00 (0.958–1.03) | 0.935 | ||
| Obesity | 1.00 (0.99–1.02) | 0.853 | ||
| Prior DTG status | ||||
| Experienced suppressed | 1.00 | 1.00 | ||
| Experienced unsuppressed | 0.91 (0.90–0.92) | < 0.001 | 0.92 (0.91–0.93) | < 0.001 |
| Naive | 1.01 (1.00-1.02) | 0.003 | 0.99 (0.98–1.01) | 0.497 |
| Duration on ART | ||||
| 24 months or less | 1.00 | 1.00 | ||
| > 24 months | 0.98 (0.97–0.99) | < 0.001 | 0.96 (0.94–0.97) | < 0.001 |
| Current DTG regimen | ||||
| Other DTG regimen | 1.00 | |||
| TDF + 3TC + DTG(TLD) | 1.01 (0.99–1.02) | 0.356 | ||
| Ever received MMD | ||||
| No | 1.00 | 1.00 | ||
| Yes | 1.23 (1.21–1.25) | < 0.001 | 1.25 (1.23–1.28) | < 0.001 |
| Exposed to PMTCT | ||||
| No | 1.00 | |||
| Yes | 1.01 (0.99–1.01) | 0.120 | ||
| History of TB treatment | ||||
| No | 1.00 | 1.00 | ||
| Yes | 0.99 (0.98–0.99) | 0.003 | 0.99 (0.98–1.01) | 0.355 |
| Malnutrition status | ||||
| No Malnutrition | 1.00 | 1.00 | ||
| Mild & moderate | 0.97 (0.94–1.01) | 0.129 | 0.98 (0.95–1.02) | 0.298 |
| Severe | 0.75 (0.63–0.89) | 0.001 | 0.77 (0.69–0.94) | 0.012 |
| Retention in care | ||||
| Retained | 1.00 | < 0.001 | 1.00 | |
| Not Retained | 0.76 (0.71–0.81) | 0.83 (0.77–0.89) | < 0.001 | |
| Facility type | ||||
| Dispensary | 1.00 | 1.00 | ||
| Health centre | 1.00 (0.99–1.01) | 0.365 | 1.00 (0.99–1.01) | 0.930 |
| Hospital | 1.01 (1.00-1.02) | 0.029 | 1.01 (0.99–1.01) | 0.060 |
| Facility ownership | ||||
| Private/FBO | 1.00 | |||
| Public | 0.99 (0.99–1.01) | 0.364 | ||
| Zone | ||||
| Central zone | 1.01 (0.99–1.02) | 0.415 | 1.00 (0.98–1.02) | 0.860 |
| Coastal zone | 0.98 (0.97–0.99) | 0.020 | 0.98 (0.96–0.99) | 0.033 |
| Lake zone | 1.03 (1.01–1.04) | 0.001 | 1.01 (0.99–1.03) | 0.227 |
| Northern zone | 1.00 (0.98–1.01) | 0.639 | 0.99 (0.98–1.02) | 0.815 |
| Southern highland | 0.99 (0.97-1.00) | 0.102 | 0.99 (0.97–1.01) | 0.437 |
| Western zone | 1.00 | 1.00 | ||
RR relative risk, CI confidence Interval, MMS multi months dispensing
In adjusted analysis, after adjusting for sex, age, WHO clinical, prior DTG status, duration on ART, ever-received MMD, history of TB treatment, Malnutrition status, Retention in care, facility type, and zone. Participants aged 15 to 19 years were 2% more likely to achieve viral suppression compared to participants aged 1 to 4 years (aRR: 1.02; 95%CI: 1.01–1.03). Also, Individuals with baseline WHO Stage I were 3% more likely to achieve viral suppression compared to individuals in WHO Stage IV (aRR: 1.03; 95%CI: 1.01–1.04) and individuals with baseline WHO stage II were 2% more likely to achieve viral suppression compared to individuals with WHO stage IV (aRR: 1.02; 95%CI: 1.00-1.04). Participants with a duration on ART of more than 24 months were 4% less likely to achieve viral suppression compared to participants with a duration of 24 months or less (aRR: 0.96; 95%CI: 0.94–0.97). Also, those participants ever received Multi month prescription on ART were 25% more likely to achieve viral suppression compared to participants not evered received multi month prescription on ART (aRR: 1.25; 95% CI: 1.23–1.28) (Table 3).
Those participants not retained in care were 17% less likely to achieve viral suppression compared to participants retained in care (aRR: 0.83; 95% CI: 0.77–0.89). Participants with severe malnutrition were 23% less likely to be HIV virally suppressed (aRR:0.77; 95%CI: 0.69–0.94) compared to their counterparts.
Discussion
Among CALHIV, the overall rate of viral suppression was 91.6%. Multivariable regression modelling revealed several factors significantly associated with viral suppression. This included age, WHO Clinical stage, prior DTG status, duration on ART, being on MMD, malnutrition status, retention and geographical zones. Specifically, older adolescents (15–19 years), WHO stage I and II, being on MMD were more likely to achieve viral suppression. Contrarily, regional disparities in viral suppression rates were observed, suggesting possible differences in program implementation or healthcare access.
We found a high (91.6%) proportion of viral suppression among CALHIV on a DTG-based regimen. Furthermore, 66.2% of previously unsuppressed became suppressed and 88.5% of previously suppressed remained suppressed. The proportion of HIV viral suppression on a DTG-based regimen CALHIV in our study is approximately similar to 91.5% and 92% as reported in Nigeria [7] and Ethiopia [5]. However, it was a bit higher compared to 84.0% and 80.0% which were reported in the USA [8] and Kenya [9]. These variations could be explained by the patient management and guidelines in viral load measurements.
Among previously unsuppressed CALHIV at baseline, 66.1% achieved viral suppression after shifting to a DTG-based regimen and among previously suppressed CALHIV at baseline, 88.4% remained suppressed. The proportion is approximately similar to studies in Italy, Ireland, and Nigeria [6–12]. Among ART-naïve participants on a DTG-based regimen, viral suppression of 91.7% after six months. The proportion is relatively similar to studies in Uganda and France [9, 10]. In addition, ART naïve participants had a higher proportion of viral suppression (93.2%) compared to ART experienced who shifted to a DTG-based regimen with 91.4%. The findings are similar to studies in western India [15], Nigeria [11], and Uganda [13]. It showed a good response to the DTG-based regimen, which may reduce the risk of developing viral resistance [16].
This study found several factors independently associated with viral suppression including duration on ART of more than 24 months.
Similar findings have been reported elsewhere in the USA [17], France [14], and Kenya [9]. It can be explained by the evidence from clinical practice, which suggests that prolonged ART can reduce viral load below the limit of detection for a long-term period [5].
We also found ‘Ever received a multi-month prescription (MMP)’ to be significantly related to viral suppression compared to participants who never received a multi-month prescription. Participants who have ever received multi-month prescriptions are 1.25 times more likely to achieve viral suppression compared to those who never received multi-month prescriptions, which is consistent with the findings of studies conducted in Ethiopia [18] and Kenya [19]. It may be the case that those who do not receive this multi-month prescription for viral suppression have poor adherence due to a drop in drug concentration in body fluids because their viral load increases because of their inability to suppress HIV replication, which in turn causes their viral load to increase.
In this study, at baseline, we also found the age of children and adolescents living with HIV to have a significant effect on viral suppression. Children and adolescents living with HIV aged 5–14 years were less likely to achieve viral suppression compared to children and adolescents living with HIV aged 1–4 years. The results are consistent with reports from the USA [20] and Zimbabwe [21]. This can be explained by the fact that adolescents and young adults living with HIV experience multiple barriers to adherence, including developmental, physical, emotional, behavioural, and social dynamic changes.
Furthermore, in this study, those not retained in care were less likely to achieve viral suppression compared to CALHIV retained in care, which mirrors the findings of the study done in South Africa [22]. This indicates that CALHIV being retained in care were more likely to achieve viral suppression compared to those not retained in regular care since adolescents seem to have lower retention rates compared to other age groups due to psychosocial and emotional challenges which are led by stigma and discrimination, peer pressure and identity development, and mental health issues.
This study utilized the nationally representative data of children and adolescents living with HIV. Hence, enough statistical power increases the precision of the estimates and makes the findings generalizable to treatment naïve and experienced CALHIV. This is the first study in Tanzania to evaluate the HIV viral suppression on a dolutegravir-based regimen and associated factors among CALHIV. Therefore, our study has provided a basis for the estimation of viral suppression amongst CALHIV on a DTG-based regimen in Tanzania.
This study has several limitations related to its retrospective nature which utilized secondary data, which might threated data quality issues which includes missing values in viral load and explanatory variables. Additionally, unmeasured confounding variables, such as underlying health status, partner behaviors, or provider-level factors could not be assessed. The inability to conduct drug resistance testing and antiretroviral drug level testing, which could have helped to determine the contributions of resistance before switching to DTG to the risk of treatment failure, especially among virally unsuppressed CALHIV on ART.
Conclusions
The proportion of viral suppression among CALHIV on a DTG based regimen in this study was 91.6%. This study showed DTG-based regimens have a good response for both naïve, previously unsuppressed, and suppressed CALHIV with significant improvement in viral suppression, particularly those in baseline WHO stage I and those who ever received a multi-month prescription, as they were more likely to achieve viral suppression. Viral suppression among CALHIV on DTG was associated with age 5–14 (years), duration on ART more than 24 months, ever received a multi-month prescription, WHO stage I, WHO stage II, experienced unsuppressed prior to DTG, not retained in care, and living in the coastal zone. Our findings underscore the importance of switching CALHIV to a DTG-based regimen as it could pave the way toward ending transmission.
Acknowledgements
Besides my supervisors, I would like to thank all members of the Department of Epidemiology and Applied Biostatistics and the National Aids, STIs, and Hepatitis Control Programme (NASHCoP) for their assistance, encouragement, constructive comments, and recommendations. I do extend my sincere gratitude to the National Aids, STIs, and Hepatitis Control Program (NASHCoP) for the permission to access patient-level information in the CTC 2 Databases.
Abbreviations
- ART
Antiretroviral therapy
- CALHIV
Children and adolescents living with HIV
- CTC
Care and treatment clinic
- DTG
Dolutegravir
- HIV
Human immunodeficiency virus
- MMP
Multi-month prescription
- NNRTI
Non-nucleoside reverse transcript inhibitor
- PI
Protease inhibitor
- VS
Viral suppression
- WHO
World Health Organization
Author contributions
AAM contributed to the study’s design, performed the formal statistical analysis, funding acquisition, investigation, methodology, resources, visualization, and drafted the manuscript. MSdB, MJM, and MJM formal analysis, visualization, writing- review and editing the final draft of the manuscript and approved the final manuscript.
Funding
The authors declare that no financial support was received for the research, authorship, and/or publication of this article.
Data availability
No datasets were generated or analysed during the current study.
Declarations
Ethical approval
The study was approved by the Kilimanjaro Christian Medical University College of Tumaini University Makumira ethical committee (No: PG 12/2021). Administrative approval was obtained from the Ministry of Health, Community Development, Elderly and Children (Ref. No PA. 87/266/02-A/97). The study was conducted under the 1964 Declaration of Helsinki and its later amendments. As the study utilized secondary data from routinely collected program data, informed consent was waived by the ethical committee. All patient data were de-identified prior to analysis to maintain confidentiality and participant codes from CTC identity numbers were used instead of names.
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
No datasets were generated or analysed during the current study.