**6. Comparison of survival curves**

The overall Kaplan-Meier survivor function estimate showed that most of the deaths occurred in the earlier months of ART initiation, which declined in the later months of follow-up. Most of the graphs did not show differences between different categories. However, relatively larger gaps are observed in covariates such as WHO clinical stage, TB co-infection, low Hgb level (<10gm/dl), and CTZ and INH prophylaxes (**Figures 1** and **2**).

#### **Figure 1.**

*Nutrition and HIV/AIDS - Implication for Treatment, Prevention and Cure*

**Variables Categories Frequency Percent** Sex Male 241 57.2

Age category <1 year 30 7.1

Primary caregiver Parents 268 63.7

Parental status Both parents are alive 260 61.8

WHO clinical staging at entry Stage I 91 21.6

TB at baseline Yes 60 14.3

Hemoglobin level at baseline <10 gm/dl 78 18.5

Absolute CD4 at baseline CD4 above threshold 239 56.9

ART adherence status Good 335 79.6

CTZ prophylaxis Yes 314 74.6

INH prophylaxis Yes 302 71.7

*Demographic and clinical characteristics and chemoprophylaxis status among children on antiretroviral* 

Female 180 42.8

1–4 years 169 40.1 5–14 years 222 52.7

Relatives 119 28.3 Guardian/orphan 34 8.0

Maternal orphan 45 10.9 Paternal orphan 31 7.4 Double orphan 84 19.9

Stage II 135 32.1 Stage III 147 34.9 Stage IV 48 11.4

No 361 85.7

≥10 gm/dl 343 81.5

Fair 33 7.8 Poor 53 12.6

No 107 25.4

No 119 28.3

CD4 below threshold 181 43.1

**5. Mean survival time after initiation of ART**

*treatment at Arba Minch Hospital and Health Center, Southern Ethiopia, 2017.*

time of 69.3 and 80.8 months, respectively.

children in the study was 82.3 (95% CI = 79.48–85.14) months.

After initiation of ART, children were followed up for a minimum of 1 and maximum of 95 months with median follow-up period of 50 (IQR = 24–80) months. At the end of follow-up, 261 (62%) of the children were alive, 43 (10.2%) were lost to follow-up, 52 (12.4%) were transferred out to other facilities, and 65 (15.4%) were reported dead. The overall mean estimated survival time after ART initiation of

There is a significantly different survival time between different factors considered in this study. Females have relatively lower survival time of 79.3 months than males with 84.6 months. Children 1–4 years of age had higher survival time of 86.8 months than those less than 1 and 5–14 years of age who had a mean survival

**6**

**Table 1.**

*The plot of the overall estimate of Kaplan-Meier survivor function among children on ART at public health facilities of Arba Minch town, Southern Ethiopia, 2017.*

#### **Figure 2.**

*Survival curves for children on ART by WHO clinical stage, hemoglobin level, and TB co-infection after start on ART at public health facilities in Arba Minch town, 2017.*

### **7. Results of the Cox proportional hazards regression model**

One important predictor of low survival time in univariable Cox regression analysis was advanced WHO staging. The risk of low survival chance in individuals with advanced disease according to WHO staging at baseline was nearly 4 times


#### *Nutrition and HIV/AIDS - Implication for Treatment, Prevention and Cure*

*Note: CTZ, Cotrimoxazole; ART, antiretroviral therapy; INH, isoniazid; TB, tuberculosis; OI, opportunisticInfections, \*p < 0.25 which are candidate for Multivariate Cox regression model.*

#### **Table 2.**

*Univariable Cox regression analysis of sociodemographic characteristics and clinical and immunological status among children who were started on ART at public health facilities of Arba Minch town, 2017.*

higher than that of those at the mild stage of the disease (P < 0.001). The risk of surviving a shorter time in individuals who had severe acute malnutrition (SAM) at baseline was nearly 2.5 times higher when compared to those with no malnutrition (P < 0.006). Patients with baseline opportunistic infections (OIs) survive nearly three 3 times shorter than those without OIs (P < 0.001), and children with TB co-infection were nearly 11 times more likely to survive shorter when compared to those without TB co-infection (P < 0.001). The risk of surviving at short duration was significantly higher with low hemoglobin level (CHR = 7.3, 95% CI = 4.47–11.9,

**9**

**8. Discussion**

**Table 3.**

*Nutritional Status and Its Effect on Treatment Outcome among HIV-Infected Children Receiving…*

**Covariate Categories AHR P-values**

Underweight 4.08 0.001

Below threshold 2.26 0.003

Yes 0.37 0.001

Yes 0.25 0.001

Fair 3.39 0.001 Poor 3.28 0.001

Nutritional status Normal 1

Absolute CD4 count Above threshold 1

INH prophylaxis No 1

CTZ prophylaxis No 1

ART adherence on follow-up Good 1

*status among children on ART at public health facilities of Arba Minch town, 2017.*

P = 0.001) and CD4 count below the threshold (CHR = 1.7, 95% CI = 1.02–2.74, P = 0.041) when starting ART compared to their counterparts. CTZ and INH had preventive effect against surviving for short duration (CHR = 0.2, 95% CI = 0.10– 0.27 P = 0.001) and (CHR = 0.1, 95% CI = 0.07–0.20 P = 0.001) when compared to

*Multivariable Cox regression analysis of sociodemographic characteristics and clinical and immunological* 

their counterparts throughout the follow-up period, respectively (**Table 2**). In multivariable Cox regression analysis, children with CD4 count below threshold for immunodeficiency at ART initiation were 2.3 times (AHR = 2.26, 95% CI = 1.32–3.88, P = 0.003) more likely to survive at shorter duration as compared to those with CD4 count above threshold. Children with low weight for age (underweight) at ART initiation were almost 4 times (AHR = 4.1, 95% CI = 2.41–6.9, P = 0.001) more likely to survive at shorter duration as compared to those with normal weight. Children that were presented for treatment with fair ART adherence and poor ART adherence were on follow-up 3.4 times (AHR = 3.4, 95% CI = 1.66– 6.9, P = 0.001) and 3.3 times (AHR = 3.3, 95% CI = 1.73–6.23, P = 0.001) and more likely to survive at shorter duration, respectively, as compared to those with good adherence on follow-up. Estimated AHR for children on INH prophylaxis and CTZ prophylaxis were 0.4 (95% CI = 0.21–0.65, P = 0.001) and 0.3 (95% CI = 0.14–0.44, P = 0.001); short duration survival hazard among children who took INH prophy-

In this study the overall mean survival time was 82.3 months (95% CI: 79.48– 85.14). The cumulative probability of survival of children on ART was 82.9% after 5 years (95% CI: 78.2%–86.7%). The major factors that affect the survival time of children with HIV/AIDS and on ART are nutritional status, absolute CD4 count below threshold, and poor/fair adherence to ART. Isoniazid prophylaxis and co-

Mean survival time in our cohort was 82.3 months (95% CI = 79.48–85.14). This was in line with the finding of a study conducted in Southwest Ethiopia [83 months (95% CI = 79–87)] [26]. However, our finding was higher when compared with study conducted in Northwest Ethiopia, which reported a survival time of 56.5 months [20]. This difference might be associated with the high proportion (74.3%) of children in this study taking CTZ prophylaxis as compared to the finding

laxis was 63% and CTZ prophylaxis 75% (**Table 3**).

trimoxazole prophylaxis were preventive factors.

*DOI: http://dx.doi.org/10.5772/intechopen.85851*

*Nutritional Status and Its Effect on Treatment Outcome among HIV-Infected Children Receiving… DOI: http://dx.doi.org/10.5772/intechopen.85851*


#### **Table 3.**

*Nutrition and HIV/AIDS - Implication for Treatment, Prevention and Cure*

Sex Male

Age group <1 year

Nutritional status Normal

Anemia No

INH prophylaxis No

CTZ prophylaxis No

ART adherence on follow-up Good

WHO clinical staging at entry Stage I and II

Functional status Working

*\*p < 0.25 which are candidate for Multivariate Cox regression model.*

Absolute CD4 count Above threshold

**Covariate/factor Categories CHR P-values**

Female 1.617 0.053\*

1–4 years 1.259 0.336 5–14 years 0.655 0.069\*

Underweight 1.903 0.010\*

Below threshold 1.293 0.041\*

Yes 2.702 0.001\*

Yes 0.408 0.001\*

Yes 0.348 0.001\*

Fair 6.256 0.001\* Poor 5.937 0.001\*

Stage III 2.360 0.009\* Stage IV 10.412 0.001\*

Ambulatory 1.302 0.350 Bedridden 1.375 0.392

AZT-based regimen 0.513 0.290 TDF-based regimen 0.562 0.404

higher than that of those at the mild stage of the disease (P < 0.001). The risk of surviving a shorter time in individuals who had severe acute malnutrition (SAM) at baseline was nearly 2.5 times higher when compared to those with no malnutrition (P < 0.006). Patients with baseline opportunistic infections (OIs) survive nearly three 3 times shorter than those without OIs (P < 0.001), and children with TB co-infection were nearly 11 times more likely to survive shorter when compared to those without TB co-infection (P < 0.001). The risk of surviving at short duration was significantly higher with low hemoglobin level (CHR = 7.3, 95% CI = 4.47–11.9,

*among children who were started on ART at public health facilities of Arba Minch town, 2017.*

*Univariable Cox regression analysis of sociodemographic characteristics and clinical and immunological status* 

ART regimens at entry D4t-based regimen 0.294 0.420

Second-line ART Evidence of TB during follow-up Yes 1.383 0.050\* No *Note: CTZ, Cotrimoxazole; ART, antiretroviral therapy; INH, isoniazid; TB, tuberculosis; OI, opportunisticInfections,* 

**8**

**Table 2.**

*Multivariable Cox regression analysis of sociodemographic characteristics and clinical and immunological status among children on ART at public health facilities of Arba Minch town, 2017.*

P = 0.001) and CD4 count below the threshold (CHR = 1.7, 95% CI = 1.02–2.74, P = 0.041) when starting ART compared to their counterparts. CTZ and INH had preventive effect against surviving for short duration (CHR = 0.2, 95% CI = 0.10– 0.27 P = 0.001) and (CHR = 0.1, 95% CI = 0.07–0.20 P = 0.001) when compared to their counterparts throughout the follow-up period, respectively (**Table 2**).

In multivariable Cox regression analysis, children with CD4 count below threshold for immunodeficiency at ART initiation were 2.3 times (AHR = 2.26, 95% CI = 1.32–3.88, P = 0.003) more likely to survive at shorter duration as compared to those with CD4 count above threshold. Children with low weight for age (underweight) at ART initiation were almost 4 times (AHR = 4.1, 95% CI = 2.41–6.9, P = 0.001) more likely to survive at shorter duration as compared to those with normal weight. Children that were presented for treatment with fair ART adherence and poor ART adherence were on follow-up 3.4 times (AHR = 3.4, 95% CI = 1.66– 6.9, P = 0.001) and 3.3 times (AHR = 3.3, 95% CI = 1.73–6.23, P = 0.001) and more likely to survive at shorter duration, respectively, as compared to those with good adherence on follow-up. Estimated AHR for children on INH prophylaxis and CTZ prophylaxis were 0.4 (95% CI = 0.21–0.65, P = 0.001) and 0.3 (95% CI = 0.14–0.44, P = 0.001); short duration survival hazard among children who took INH prophylaxis was 63% and CTZ prophylaxis 75% (**Table 3**).

#### **8. Discussion**

In this study the overall mean survival time was 82.3 months (95% CI: 79.48– 85.14). The cumulative probability of survival of children on ART was 82.9% after 5 years (95% CI: 78.2%–86.7%). The major factors that affect the survival time of children with HIV/AIDS and on ART are nutritional status, absolute CD4 count below threshold, and poor/fair adherence to ART. Isoniazid prophylaxis and cotrimoxazole prophylaxis were preventive factors.

Mean survival time in our cohort was 82.3 months (95% CI = 79.48–85.14). This was in line with the finding of a study conducted in Southwest Ethiopia [83 months (95% CI = 79–87)] [26]. However, our finding was higher when compared with study conducted in Northwest Ethiopia, which reported a survival time of 56.5 months [20]. This difference might be associated with the high proportion (74.3%) of children in this study taking CTZ prophylaxis as compared to the finding of the study conducted in Northwest Ethiopia (52.3–70.4%), and the difference might also be associated with increased access to ART services.

The cumulative probability of survival of children on ART in our study was 82.9% after 5 years (95% CI: 78.2–86.7%). This was comparable with the report of a study conducted in Felege Hiwot Referral Hospital, Bahir Dar, Northern Ethiopia (83%) [27] and another one in Northwest Ethiopia (83%) [20]. However the cumulative survival probability from our study was much lower than that of the reports from Adama Referral Hospital and Medical College, Central Ethiopia (91.6%) [19], and Wolaita zone health facilities, Southern Ethiopia (92%) [20]. These variations between our study and those from central and Southern Ethiopia may have something to do with the variation in the quality of care provided at different institutions.

In this study we found that having CD4 cell count below the threshold level was significantly associated with an increased probability of having short duration of survival among the children. This concurs with the findings of different studies previously done in Ethiopia [20, 28]. The similarity might be related to the fact that children, in our series, with absolute CD4 counts below the threshold level are more prone to OIs like TB. Another possible explanation could be ART was initiated in an advanced HIV stage (stages III and IV) where immunity of the children was already compromised.

Another covariate that had a significant effect on survival time was adherence to ART. The HR for poor adherence was 2.1 times, and the HR for fair adherence was 2.2 times more likely to result in short duration of survival compared to children with good adherence. This finding was supported by studies conducted in Northwest Ethiopia [28] and Wolaita zone health facilities [20]. The poor adherence might be due to insufficient counseling and education of caregiver/patient.

The initiation of CTZ and INH at the start of ART in our cohort was associated with a longer duration of survival. This finding concurred with that of the studies conducted in Felege Hiwot Referral Hospital, Northern Ethiopia [20], and rural Mozambique [29]. The possible reason for higher risk of shorter survival time among children who did not receive CTZ at ART initiation could be due to occurrence of OIs such as *Pneumocystis pneumonia*, toxoplasmosis, bacterial pneumonia, sepsis, and diarrhea. Co-trimoxazole prophylaxis should be given at the initiation of ART to reduce OI and associated short duration survival among HIV-positive children on ART, thereby improving their survival.

The hazards of short survival time for children on INH prophylaxis was 0.38, which means that, in those children who take INH prophylaxis, the hazard of short duration of survival was reduced by 62%. This finding corroborates the finding of the study conducted in Mizan-Aman General Hospital, in Southern Ethiopia [26], and that of a double blinded, placebo-controlled trial on INH efficacy among HIV children infected in Cape Town, South Africa [30]. A possible reason could be INH prophylactic therapy (IPT) prevented the occurrence of TB.

There are some strengths and limitations of this study. The strengths of this study are the use of standard measurements which enabled to make the comparison of findings with other national and international literatures to be valid. In addition, considering long duration of follow-up period of children on ART and the inclusion of important predictors like CTZ, INH and nutritional status also add to the strength to this study. Since our study is retrospective based on available records, excluding those with incomplete information, survival time might be underestimated.

#### **9. Conclusion**

In general, this study showed that the probability of survival of children on ART was 73.9% after 96 months and the overall mean survival time was 82.3 months.

**11**

*Nutritional Status and Its Effect on Treatment Outcome among HIV-Infected Children Receiving…*

We would like to say thank you very much to the health facilities administrator of the hospital and health center, health professionals, and data collectors who

The authors declare that there was no competing interest in connection to this

NB conceived and designed the study, developed data collection instruments, and supervised data collection. NB and SH participated in the testing and finalization of the data collection instruments and coordinated study progress. NB and SH performed the statistical analysis; SH wrote all versions of the manuscript. All

The main independent predictors of the survival time were nutritional status, absolute CD4 count below threshold, poor/fair adherence to ART, and absence of INH prophylaxis and CTZ prophylaxis. However, sex, age, advanced disease according to WHO clinical stage, and presence of TB at baseline were not predictors of survival time. Therefore, children living with HIV should be encouraged to take prophylaxis drugs like CTZ and INH. This could be achieved by collective efforts of all concerned bodies on high-risk groups such as children with OI especially TB after initiation of ART and a careful monitoring and follow-up of the children.

*DOI: http://dx.doi.org/10.5772/intechopen.85851*

**Acknowledgements**

contributed to this work.

**Competing interest**

research and its result.

**Authors' contribution**

**Acronyms and abbreviations**

ART antiretroviral therapy AHR adjusted hazard rate

FMOH Federal Ministry of Health HIV human immune virus

NNRT nonnucleated reverse transcripts SAM severe acute malnutrition UNICEF United Nations Children's Fund WHO World Health Organization

authors read and approved the final manuscript.

AIDS acquired immune deficiency syndrome CPT co-trimoxazole preventive therapy

*Nutritional Status and Its Effect on Treatment Outcome among HIV-Infected Children Receiving… DOI: http://dx.doi.org/10.5772/intechopen.85851*

The main independent predictors of the survival time were nutritional status, absolute CD4 count below threshold, poor/fair adherence to ART, and absence of INH prophylaxis and CTZ prophylaxis. However, sex, age, advanced disease according to WHO clinical stage, and presence of TB at baseline were not predictors of survival time. Therefore, children living with HIV should be encouraged to take prophylaxis drugs like CTZ and INH. This could be achieved by collective efforts of all concerned bodies on high-risk groups such as children with OI especially TB after initiation of ART and a careful monitoring and follow-up of the children.
