Pattern of CD4 + T cell recovery and determinants of HIV infected individuals receiving highly active antiretroviral treatment in Mekelle Hospital, Tigray Northern Ethiopia; Retrospective study

doi:10.21203/rs.3.rs-2470790/v1

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Pattern of CD4 + T cell recovery and determinants of HIV infected individuals receiving highly active antiretroviral treatment in Mekelle Hospital, Tigray Northern Ethiopia; Retrospective study

https://doi.org/10.21203/rs.3.rs-2470790/v1

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Background: With the advent of antiretroviral treatment, HIV related morbidity and mortality have tremendously decreased. However, some HIV patients on ART don’t optimally respond to the ART regimen to restore the immunity. This study was aimed to determine the pattern of CD4⁺ T cell recovery and determinants of HIV infected individuals receiving the ART in Mekelle Hospital, Tigray northern Ethiopia.

Methods: A hospital based retrospective cross-sectional study was conducted from January, 2010 to August, July 2020 among HIV positive individuals on ART follow up. Data were collected using pre-tested structured questionnaire by trained data collector. Statistical analysis was performed using SPSS V. 20. Bivariate and multivariate analyses were performed to identify the possible predictors for immune reconstitution after ART administration. P-values < 0.05 was considered statistically significant.

Results: Of the total 424 study participants, 248(58%) were females. The mean age of the study participants was 37+9 (mean + sd). The median time of ART follow up was 60 (IQR: 36-84) months and the recent median CD4⁺ T-cell count was 388 (IQR; 254-527) cells/µl. The CD4 cell count increment compared to pre-ART was 166 cells/µl of blood. Age ranges 25-34 years (AOR 2.62, 95%CI: 0.82-8.35), CD4⁺ T-cell count >200 cells/µl at baseline (AOR 3.53, 95%CI: 2.23-5.58), duration of ART follow up at 12, 48 and 49 and above months respectively (AOR 8.053, 95%CI:1.45-44.84; 4.82, 95%CI:1.16-20.11); and (AOR 6.36, 95%CI:1.63-24.77), and TDF-3CT-Efv ART regimen combination (AOR 2.29, 95%CI:1.32-3.97) were found predictors significantly associated with CD4⁺ T-cell recovery after long term ART uptake, which characterized by >350 cells/µl increments.

Conclusions: The immune restoration of HIV positive individuals depends on the length of ART follow up time and CD4⁺ T-cell level during the initiation. Moreover, individuals who were taking TDF-3CT-Efv ART drug combination demonstrated a rapid CD4⁺ T-cell restoration than these who were taking other ART drug regimens.

CD4+ T cell

HIV

individuals

antiretroviral treatment

Human ImmunoDeficiency Virus (HIV) is a major public health concern worldwide [1]. In 2019, around 38 million people are living with HIV [2] and globally 25.4 million people living with HIV are receiving Anti-Retroviral Therapy(ART). In 2019, the incidence and mortality of HIV infected people were 1.7 million and 690, 000 respectively worldwide. About two third of the HIV infected individuals are found in African region [2]. Moreover, in 2018, 470,000 people are died from HIV/AIDS related illness in Africa region [1]. In Ethiopia, according to the 2017 report, 718,498 and 426,472 people are living with HIV and receiving ART respectively with a coverage of 59%.

Even though HIV related morbidity and mortality has reduced dramatically with introduction of combination ART therapy in 1996, some patients didn’t recover their optimum immune response following ART, leading to HIV/AIDS related death [4, 5]. CD4 + T-cell count is an immunological surrogate marker used to assess the immune function of HIV infected individuals before the treatment initiations and during ART follow ups [6]. It is also the most important laboratory indicators of immune function and predictor of subsequent disease progression and survival [7, 8]. Immune restoration of HIV infected individuals is achieved through optimum viral RNA suppression, with ultimate increase in CD4 + T-cell counts in majority of patients following combination ART uptakes. But a significant number of patients who were taking ART didn’t restore the optimum immune recovery, which accelerated to HIV/AIDS related morbidity and mortality [9]. Moreover, despite successful viral suppression, some patients fail to experience immune reconstitution following ART administration. Approximately, half of the ART treated patients fail to recover their CD4 + T-cell levels above 500 cells/µl, and up to 16% or 20% may not be achieved a CD4 + T-cell counts > 200 cells/µl even with long term therapy [10].

There are many controversial findings for immune restoration following combination ART regimen in HIV infected individuals [11, 12, 13]. Some studies indicated that the baseline CD4 cell count is affected by the rate of immune regain after ART administration [14, 8, 15, 16]. Unlike to the above findings, others didn’t found any evidence [17]. There are also some evidences that younger age groups have the tendency to rapidly raise the CD4 T-cell count following the ART initiation [18, 19]. However, as to our knowledge, there was no previous report regarding the pattern of CD4⁺ T-cell recovery and determinants for immune restoration following ART in Tigray region, north Ethiopia. Therefore, this study was designed to evaluate the pattern of CD4⁺ T cell recovery and determinants factors immune restoration following ART in Mekelle Hospital, Tigray, northern Ethiopia

Study setting and design

A facility based retrospective cross-sectional study was conducted from January 2010 to August, 2020 among HIV positive individuals on ART follow up. This study was conducted in Mekelle general hospital which is located in Tigray region, northern Ethiopia. The region has seven administrative zones, one special zone, 52 districts and 799 Kebeles. Based on the 2007 census projection, Tigray has an estimated total population of 4.8 million people over an area of 50,078.64 square kilometers [20]. Mekelle general hospital is the largest ART center in the region which is serving for about 8399 HIV infected individuals on ART follow up. Our study participants are all HIV positive who were enrolled to ART follow up, and who have a minimum of 6 months ART follow up, and visited the ART clinic during the study period.

Inclusion criteria

All HIV positive individuals who are on ART follow up for at least 6 months, 18+ years old and had a baseline CD4+ T-cell measurements were included in the study.

Sample size and sampling technique

The sample size (n) was calculated using single population proportion formula by assuming the CD4⁺ T-cell recovery is 50%. The calculated sample size was 385. Considering 10% of non-response rate, the final calculated sample size was 424. Simple random sampling method was used to select the study participants. The sampling interval (K) value was calculated by dividing the total number HIV infected individuals who were expected to visit the ART center during the study period. Hence, a total of 1389 HIV positive individuals were visited the ART clinic during the study period. The first study participant was selected using a lottery method among the first three patients (K) and every third from list was included in the study.

Data collection

The socio-demographic characteristics like sex, age, marital status, residence, education, occupation and clinical information were collected by trained data collector using structure questionnaire. Moreover, the baseline CD4⁺ T-cell count, recent CD4⁺ T-cell count, combination ART regimens and duration of ART follow up were collected from patient’s record chart.

Statistical analysis

Statistical data analysis was performed using SPSS V.20. Data were summarized using the median and interquartile values for the continuous variables; and number and percentage were used to describe categorical variables. The baseline CD4⁺ T-cell counts were grouped in to CD4⁺ T-cell count < 200 cells/µl and > 200 cells/µl. Individuals with a baseline CD4⁺ T-cell count < 200 cells/µl was considered as severely immune compromised individuals [21]. In this study the pattern of baseline CD4⁺ T-cell counts were indicated for the majority of the study participants were started ART with advanced or sever immune suppression [22]. Nonetheless, there was no clear consensus about the definition of optimal immune reconstitution, the recent CD4⁺ T-cells were classified in to two groups with the cut of value <350 cells/µl and > 350 cells/µl following the ART combination regimen. Factors associated with immune reconstitution were determined using bivariate and multivariate logistic regressions. The association between each predictable variables and the outcome variables were determined using bivariate analysis. All predictable variables with p-value less than 0.05 in the bivariate analysis were entered to the multivariate model to identify the predictable variables for CD4⁺ T-cell count > 350 cells/µl. But, before building the final model, multi co-linearity effect was assessed using linear regression and mean VIF >5 was used as cut off point. The final model was then tested for its goodness of fit by Hosmer and Lemeshow and p-value > 0.05 was the best fit [23]. Odds ratio was used to measure the strength of the association. Finally, variables that have been shown statistical significant association at p< 0.05 were identified as independent predictors for CD4⁺ T-cell count > 350 cells/µl.

Ethical consideration

Ethical clearance was obtained from Tigray health research institution, institutional review board (THRI-IRB). Official written letter was also obtained from Tigray health research institute. The present study has no direct contact with the patients or patient’s sample. The data were collected by document reviewing available at THRI database. Thus, the need for informed consent from each patients’ medical records was waived.

Socio-demographic characteristics of the study participants

This study included 424 eligible study participants, of these, 248(58%) were female participants. The mean age of the study participants was 37+9 (mean + sd) ranging from 19 to 68 years. Majority of the participants were married 227(54%) and urban residents 406(96%). Majority, 94(22%), of the study participants were housewife, and only 61(14%) were civil servants (Table 1)

Table 1: Socio-demographic characteristics of the study participants

Variables	N=424	Frequency N (%)
Sex	Female	248(58)
Sex	Male	176(42)
Age	18-24	19(4.5)
	25-34	131(31)
	35-44	180(42.5)
	>=45	94(22)
Residence	Rural	18(4)
	Urban	406(96)
Marital status	Single	59(13)
	Married	227(54)
	Divorced	91(22)
	Widowed	47(11)
Education	Illiterate	106(25)
	Elementary	143(34)
	Secondary	106(25)
	Certificate& above	69(16)
Occupation	Farmer	30(7)
	Merchant	62(15)
	Civil servant	61(14)
	Driver	20(5)
	House wife	94(22)
	Others*	157(37)

Clinical characteristics of the study participants

The majority, 414(98%), of the study participants were on first-line ART combination regimen, and the remaining 10(2%) were on second-line. Of the study participants, 233(55%) had a baseline CD4⁺ T-cell count >2000 cells/µl, ranges 200-349 cells/µl, of blood. Majority of participants had recent CD4⁺ T-cell count 350-499 cells/µl of blood (Table 2). Around 57% of the study participants were attended ART follow up for more than 49 months (> 4 years), and 166(40%) were taking a TDF-3CT-Efv ART combination regimen. One hundred sixty (38%) of the study participants had a baseline CD4⁺ T-cell count <200 cells/µl of blood.

Table 2: Clinical characteristics of study participants

Characteristics- N=424	CD₄ cell count/ µl	Frequency N (%)
Baseline CD4 cell count	<100 cells/µl	41(9.7)
	100-199 cells/µl	123(29)
	200-349 cells/µl	233(55)
	350-499 cells/µl	22(5.1)
	>=500 cells/µl	5(1.2)
Recent CD4 cell count	<100 cells/µl	16(4)
	100-199 cells/µl	55(13)
	200-349 cells/µl	105(24.8)
	350-499 cells/µl	131(30.9)
	>=500 cells/µl	117(27.6)
CD4 cell count (median)	Baseline, median(IQR)	222(160-310)
CD4 cell count (median)	Recent , median(IQR)	387.5(254-526.75)
ART type	First line ART	414(98)
ART type	Second line ART	10(2)
Duration of ART follow up (months)	<=6 month	13(3)
	7-12month	20(5)
	13-24 month	45(11)
	25-36 month	40(9)
	37-48 month	66(16)
	>=49month	240(57)
1^st Line combination ART regimens	AZT-3CT-Nuv	111(27)
	AZT-3CT-Efv	48(12)
	TDF-3CT-Nuv	89(21)
	TDF-3CT-Efv	166(40)

Immune Recovery after ART

The median CD4⁺ T-cell count for the immunological failures was 65(IQR:53-88) cells/µl of blood. Thirty-seven (9%) of the study participants had a baseline CD4⁺ T-cell counts of <100 cells/µl, of these, 4% were remained <100 cells/µl after 6-months ART follow up. One hundred sixty (38%) of the study participants were with a baseline CD4⁺ T-cell count <200 cells/µl and after 6 months of ART follow, only 71(18%) of them were remained the same, <200 cells/µl.

CD4+ T-cell Recovery after the ART Follow up

At baseline, the median CD4⁺ T-cell count was 222.5 (IQR; 160-310) cells/µl. However, the recent median CD4⁺ T-cell measurement was 388 (IQR; 254-527). The median duration of ART follow-up was 60 months (IQR: 36-84). At 6 months of ART follow up, the median CD4⁺ T-cell count was 319(IQR:113.5-698) cells/µl, where 69 cells/µl increment from the baseline. Similarly, the CD4⁺ T-cell count at 12 months of ART follow up was reached to 403(IQR:289 - 470), 153 cells/µl tall from the baseline. Moreover, by 24, 36, 48, 49 and above months of ART follow us, the median CD4⁺ T-cell counts were raised to 392, 417, 427, and 436 cells/µl respectively (Fig 1).

In bivariate analysis gender, age, occupation, baseline CD4⁺ T-cell count, duration of ART follow-up and 1^st line ART regimen have showed statistically significant association with the CD4⁺ T-cell count restoration to > 350 cells/µl, P < 0.05. These variables were entered in to multivariate logistic regression model to identify the possible predictors associated with CD4⁺ T-cell recovery, > 350 cells/µl increase. Multivariate analysis showed that age range 25-34 years AOR=2.617(95% CI: 0.821-8.348, P=0.001), CD4⁺ T-cell count >200 cell/µl at baseline AOR=3.527(95%CI: 2.231-5.576, P=0.001), duration of ART follow up at 12, 48 and 49 and above months respectively AOR=8.053(95%CI: 1.446-44.842, P= 0.017), AOR=4.820 (95%CI: 1.155-20.111, P=0.030), AOR=6.362(95%CI: 1.634-24.771, P=0.008) and ART regimen combination of TDF-3CT-Efv AOR=2.288(95%CI: 1.318-3.970, P=0.003) ) were found significantly associated with the CD4⁺ T-cell count increment by > 350 cells/µl at P <0.05 (Table 3).

The HIV positive individuals in the age group range 25-34 years were 2.6 times more likely recover their CD4⁺ T-cells count than out of this age range in the post ART initiation. Individuals with a baseline CD4⁺ T-cell count >200 cells/µl of blood were 3.5 times more likely to increase by 350 cells/µl than those <200 cells/µl of blood. Moreover, those who had ART follow up 7-12 months, 37-48 months, and 49 months and above were 8, 4.8 and 6 times more likely to recover their CD4⁺ T-cells count by 350 cells/µl of blood respectively. Similarly, TDF-3CT-Efv ART combination regimen were 2.3 times more likely to restore CD4⁺ T-cells, by 350 cells/µl of blood, than these taking other drug categories.

Table 3; Bivariate and Multivariate analysis of variables associated with CD4+ T cell count > 350 cells /µl among HIV infected individuals receiving ART

Variables		CD4⁺ T-cell count > 350 cells/µl			COR(95% C.I)	AOR(95% C.I)	P. value
Variables		Total (N= 424)	Yes N(%)	No N(%)	COR(95% C.I)	AOR(95% C.I)	P. value
Sex*⁺	Female	248(58)	153(62)	95(38)	1.648(1.114-2.436)	1.11(0.65-1.88)	0.708
Sex*⁺	Male	176(42)	87(49)	89(51)	1	1
Age*^+a	18-24	19(4.5)	13(68)	6(32)	2.683(0.939-7.661)	2.62(0.82-8.35)	0.104
	25-34	131(31)	92(70)	39(30)	2.921(1.680-5.076)	3.01(1.58-5.71)	0.001
	35-44	180(42.5)	93(52)	87(48)	1.323(0.802-2.184)	1.21(0.69-2.13)	0.506
	>=45	94(22)	42(45)	52(55)	1	1
Residence	Rural	18(4)	8(44)	10(56)	1
Residence	Urban	406(96)	232(57)	174(43)	1.667(0.644-4.311)
Marital status	Single	59(13)	33(56)	26(44)	0.788(0.361-1.720)
	Married	227(54)	132(58)	95(42)	0.862(0.453-1.643)
	Divorced	91(22)	46(50.5)	45(49.5)	0.634(0.310-1.300)
	Widowed	47(11)	29(42)	18(38)	1
Education	Illiterate	106(25)	59(56)	47(44)	1
	Elementary	142(34)	77(54)	66(46)	0.929(0.561-1.540)
	Secondary	106(25)	60(57)	46(43)	1.039(0.604-1.788)
	Certificate& above	69(16)	44(64)	25(36)	1.402(0.752-2.613)
Occupation*⁺	Farmer	30(7)	11(37)	19(63)	0.478(0.213-1.070)	0.40(0.16-1.02)	0.06
	Merchant	62(15)	36(58)	26(42)	1.143(0.631-2.071)	1.48(0.76 -2.90)	0.249
	Civil servant	61(14)	47(77)	14(23)	2.772(1.412-5.441)	1.46(0.95-1.60)	0.135
	Driver	20(5)	7(35)	13(65)	0.445(0.168-1.174)	0.28(0.09-1.86)	0.127
	House wife	94(22)	53(64)	41(44)	1.067(0.638-1.786)	0.86(0.46-1.61)	0.635
	Others#	157(37)	86(55)	71(45)	1
Baseline CD4count*^+a	<200 cells/µl	160(36)	64(40)	96(60)	1	1
Baseline CD4count*^+a	>=200 cells/µl	271(64)	176(67)	88(33)	3.00(1.997-4.506)	3.53(2.23-5.58)	0.001
Type of ART	1^st line ART	414(97.6)	234(56)	180(44)	1.154(0.321-4.150)
Type of ART	2^nd line ART	10(2.4)	6(60)	4(40)	1
Duration ART (months)*^+a	<=6 month	13(3)	5(39)	8(61)	1	1
	7-12month	20(4.7)	14(70)	6(40)	6.400(1.338-30.606)	8.05(1.45-44.84)	0.017
	13-24 month	45(10.6)	17(38)	28(62)	0.971(0.273-3.457)	1.84(0.42-8.07)	0.421
	25-36 month	40(9)	22(55)	18(45)	1.956(0.544-7.0208)	2.52(0.58-10.92)	0.218
	37-48 month	66(15.6)	36(55)	30(45)	1.920(0.568-6.490)	4.82(1.16-20.11)	0.030
	>=49month	240(57)	145(60)	95(40)	2.442(0.776-7.689)	6.36(1.63-24.77)	0.008
First line ART regimen*^+a	AZT-3CT-Nuv	113 (27)	54(48)	59(52)	1	1
	AZT-3CT-Efv	48(11)	28(58)	20(42)	1.530(0.773-3.026)	1.55(0.73-3.31)	0.259
	TDF-3CT-Nuv	89(21)	47(53)	42(47)	1.223(0.701-2.133)	1.37(0.72-2.58)	0.335
	TDF-3CT-Efv	166(39)	106(64)	60(36)	1.930(1.187-3.139)	2.29(1.32-3.97)	0.003

#Self-employee, daily work, student & commercial sex workers, *statistically significant at p<0.2, COR= crude odds ratio, ⁺variables included in multivariate model, astatically significant at P < 0.05, AOR= Adjusted odds ratio.

The median recent CD4⁺ T-cell count of the study participants was showed an increment by 166 cells/µl, reaching to 388 cells/µl. The median change in CD4⁺ T-cell count of this study was higher compared to the studies in Nigeria and Ethiopia (Jigiga) [17, 24], and lower than compared to other study findings done elsewhere [14.19]. Thought 56% of the study participants with baseline CD4⁺ T-cell count < 200 cells/µl were restored the CD4⁺ T-cells count to ≥ 200 cells/µl after at least 6 months of ART initiation, none of them were reached ≥ 500 cells/µl, which is consistent with reports elsewhere [8, 25–27]. In contrast, a retrospective study reported that 28.4% individuals with CD₄ count < 200 cells/µl at baseline raised to 500 cells/µl or greater in long term ART follow up [19]. The different might be explained due to variation in the duration of ART follow up. Inadequate CD4⁺ T-cells restoration may possibly associate with increased intrinsic CD4⁺ T-cell depletion, thymic and lymphoid differentiation dysfunction of HIV infected individuals.

Immunological failure was characterized by persistent low CD4⁺ T-cell count < 100 cells/µl after ART initiation [3, 9]. In this study, the median CD4⁺ T-cell count of the individuals categorized under the immunological failure was 65(IQR: 53–88) cells/µl. However, after the ART initiation, the proportion of HIV positive individuals with CD4 cell count < 100 cells/µl in two or more consecutive measurements was drastically reduced by 96% after ART administration, which was consistent with other studies conducted in Ethiopia [19, 28]. On the other side, our result is higher compared to the other studies [29, 30]. The difference might be due to variation in immunological status of the study participants and ART follow up duration. Moreover, various studies underlined that low CD4⁺ T-cells count before ART initiation was the most determinant predictor for immunological failure among HIV patients [18]. In addition, one of the possible reasons for poor immune recovery during ART could due to the persistent CD4⁺ T cells cytolysis as a consequence of residual viral replication [31].

At 6 months of ART follow up, the median CD4⁺ T-cell count was 319 cells/µl, raised on average by 69 cells/µl from the baseline and this was similar with other studies [23]. By 12 months of ART follow up, the median CD4⁺ T-cell count was steadily reached to 403 cells/µl which is increased by 153 cells/µl from the baseline count. Moreover, by the 48, 49 months and onward of ART follow up, the median CD4⁺ T-cell count was 427 and 436 cells/µl respectively which is implied a continuous increment of the CD4⁺ T-cell count following ART initiation, which is consistent with other similar studies [10, 15, 25].

Comparing to the other age groups, age group 25–34 years were more likely recover their CD4⁺ T-cells after ART combination therapy, P = 0.001. This is indicated that HIV infected individuals at younger age groups have more possibility for the rapid recovery of CD4⁺ T-cells compared to the older age groups in post ART initiation time. This is comparable with other studies in Zimbabwe, Uganda, Ethiopia, France and Australia [14, 15, 19, 32, 33]. Other studies were also demonstrated that the younger age group who had a baseline CD4⁺ T-cell count < 500 cells/µl have shown rapid recovery and longer life expectancy comparable to these having > 500 cells/ µl[5, 18]. Moreover, studies in China indicated that patients who were started ART at younger age were more likely to achieve their optimum immune recovery compared to the older age groups [16, 26]. Other similar studies were also suggested that CD4⁺ T-cell count gain was slower with increasing age during the ART initiation time [31, 34–36]. In contrast, other studies reported that the younger age of HIV infected individuals were less likely regain immune reconstitution than the older age groups (50 years or greater) following ART administration [37, 38].

HIV infected individuals having a baseline CD4⁺ T-cell count ≥ 200 cells/µl were more likely increased their CD4⁺ T-cells, above 350 cells/µl, compared to those with a baseline CD4⁺ T-cell count < 200 cells/µl following ART initiation, P = 0.001. A long prospective cohort study suggested that ART treated individuals with CD4 cell count ≥ 200 cells/µl at ART initiation demonstrated a greater tendency to recover CD4⁺ T-cells faster than those who had a normalized CD4⁺ T-cells count [8, 25, 39–41]. A systematic review study reported that individuals with CD4 T cell count, at baseline, ≥ 350 cells/µl had a greater likelihood of immune recovery after ART administration, reducing the chance to progression to AIDS or death [42]. Moreover, similar studies finding indicated that individuals with higher pre-ART CD4⁺ T-cell count have shown optimum immune reconstitution following ART initiation [15, 16, 26, 33, 43–45]. Besides, evidence also indicated that earlier initiation of ART is the best opportunity for CD4 + T-cell recovery, and immune system preservation which decreased CD4 + T-cell depletion, lower rate of AIDS events or opportunistic infections, and higher capacity for the reconstitution of the immune system in general [22]. In contrast, some studies suggested that HIV patients with low pre-ART CD4⁺ T-cell count indicated a rapid CD4⁺ T-cell recovery, and higher long term mean CD4⁺ T-cells in post-ART [11, 14, 30, 35]. Unlike the above findings, few studies indicated that the baseline CD4⁺ T-cell count have no significant association with immune recovery following ART administration [27,51]. The variation might be due to the difference in duration of ART initiation time (early Vs late), lower rate of AIDS events, and higher rate of immune reconstitution system compared to among patients with low CD4 T-cell at ART initiation [18]. Though, the variation of the findings need further well-designed prospective study, majority of the studies reported that the higher CD4⁺ T-cell count at baseline, the greater is the ART impact on CD4⁺ T-cell recovery [13, 19, 24, 30, 46, 47].

The CD4⁺ T-cell count is more likely increased by 12 months of follow up compared to those on the first 6 months of ART initiation, P = 0.017. In line with this, a number of retrospective longitudinal studies demonstrated there were a rapid CD4⁺ T-cell recovery in the first one year of ART initiation [15, 29, 37]. Another finding also indicated that CD4⁺ T-cell recovery was steady increased by 12 months, and continually increased thereafter until it was reached to a plateau for optimal immune restoration following ART administration [21]. Similarly, the CD4 T-cells recovery was very optimal after 48 months, 49 months and onwards of ART initiation.

This is indicated a sustained increase in CD4⁺ T-cell count throughout their ART follow ups. Moreover, prospective cohort studies in London and South Africa have shown consistent findings on immune reconstitution characterized by increased CD4⁺ T-cells throughout their months of ART follow up [10, 25]. An observational cohort studies conducted in China and Ethiopia (Gondar University hospital) shown that HIV patients on ART for longer time have shown optimum immune recovery [10, 16, 22, 25, 41, 43, 48]. Besides, many study findings also described as the length of ART follow up time increases the CD4⁺ T-cell count is also continually increased until it reached a plateau or threshold, which is consistent with our study [38, 44, 45, 47, 48].

These HIV patient on 1st line ART drug combination, TDF-3CT-Efv, were more likely to restore their CD4⁺ T-cell levels compared to those on other 1st line drug categories, P = 0.003, which comparable to reports from Australia and Ethiopia [15, 43]. Moreover, studies conducted in Zambia, Ghana and China also indicated that HIV infected individuals took tenofovir based ART combination regimen were experienced higher level of CD4⁺ T-cell restoration than on Zidovudine regimen [343, 37, 47]. Similarly, TDF based ART regimen is the preferable ART regimen for optimal viral suppression, rapid CD4⁺ T cell recovery and continual improvement of the depleted CD4⁺ T-cells following long term AR duration [49, 50]. A contradicting report on the other side demonstrated that a TDF based ART regimen did not indicate a significant impact on immune reconstitution compared to the other ART regimens [48]. The difference might be attributed to the duration of time on ART, and immunological status of patients during ART initiation though it needs a well-designed prospective study. None of the variables like sex, residence, marital status occupation and educational status have shown statistical significant association for CD4⁺ T cell recovery following ART uptake. The limitation of this study is lacking to describe the clinical HIV/AIDS stage and virological status of the patients at baseline and after ART administration.

Starting ART at higher (> 350 cells/µl) CD4⁺ T-cell count is predominantly necessary for attainment of optimal CD4⁺ T-cell recovery in post-ART initiation. Individuals who started ART at younger age had shown a rapid recovery and less overall CD4⁺ T-cells depletion. CD4⁺ T-cell count is rapidly increased in the first year of the ART initiation and continually with the of duration of ART follow-up increases. Moreover, individuals who were taking TDF based ART combination regimen were experienced faster CD4⁺ T-cell recovery compared to those in other 1st line categories. Therefore, the program should give emphasis to the TDF-3CT-Efv 1st line ART combination regimen for better outcome. In addition, ART initiation should start at > 350 cells/µl of CD4⁺ T-cell counts for the best immune system restoration.

Ethical approval and consent to participate

Consent for publication

All authors are agreed on the overall preparation of the manuscript and submission for publication on ADIS research and Therapy

Availability of data and materials

The data and materials are available with the authors and delivered upon the a request.

Competing interests

All authors declared no conflict of interest

Funding

As it is retrospective data, there was no specific fund for this study

Acknowledgments

We would like to express our thanks and appreciation to the data collectors for their fully responsibility and commitment. We would like also to acknowledge Mekelle Hospital Chief Executive Officer and ART clinic data manager for the permission and cooperation with the data collector team.

Author Contributions

Conceptualization: Letebrhan Weldemhret, Abraham Aregay, Hadish Bekurtsion, Gebremicheal Gebreegziabher, Tsehaye Asmelash, Dawit Gebreegziabher Hagos

Data curation: Letebrhan Weldemhret, Abraham Aregay, Hadish Bekurtsion, Gebremicheal Gebreegziabher, Tsehaye Asmelash, Dawit Gebreegziabher Hagos

Formal analysis: Letebrhan Weldemhret, Abraham Aregay, Hadish Bekurtsion, Gebremicheal Gebreegziabher, Tsehaye Asmelash, Dawit Gebreegziabher Hagos

Methodology: Letebrhan Weldemhret, Abraham Aregay, Hadish Bekurtsion, Gebremicheal Gebreegziabher, Tsehaye Asmelash, Dawit Gebreegziabher Hagos

Writing – original draft: Letebrhan Weldemhret, Abraham Aregay, Hadish Bekurtsion, Gebremicheal Gebreegziabher, Tsehaye Asmelash, Dawit Gebreegziabher Hagos

Writing – review & editing: Letebrhan Weldemhret, and Dawit Gebreegziabher Hagos

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No competing interests reported.

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Pattern of CD4 + T cell recovery and determinants of HIV infected individuals receiving highly active antiretroviral treatment in Mekelle Hospital, Tigray Northern Ethiopia; Retrospective study

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Abstract

Figures

Introduction

Materials And Methods

Study setting and design

Inclusion criteria

Sample size and sampling technique

Data collection

Statistical analysis

Ethical consideration

Results

Socio-demographic characteristics of the study participants

Clinical characteristics of the study participants

Immune Recovery after ART

CD4+ T-cell Recovery after the ART Follow up

Discussion

Conclusion

Declarations

References

Additional Declarations

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