Hepatitis B and C Immunological and Molecular Parameter Analysis in HIV-Positive Patients Undergoing Antiretroviral Therapy at Saint Camille Hospital in Ouagadougou (HOSCO), Burkina Faso

Knowledge of the clinical and biological profile of patients infected with HIV and hepatitis B and/or C is essential in order to identify and implement effective management strategies. Methods: This was a retrospective descriptive study from January 01, 2016 to June 01, 2021. Adult patients aged at least 18 years infected with HIV type 1 and/or 2, naïve to ARV treatment. Univariate analyses were assessed using Pearson’s Chi2 test. The Student Newman test was used for comparison between groups using R software version 4.0.2. Objective: To draw up the epidemiological, clinical, paraclinical and evolutionary profiles of HIV-treated-patients in relation to HIV/HBV and HIV/HCV co-infections in order to allow the identification and the implementation of effective management strategies. Results: Of the 379 patients included 280 How to cite this paper: Ilboudo, D.P., Savadogo, W.W.E.K., Zohoncon, T.M., Savadogo, E., Hien, Y.E., Traore, L., Ouermi, D., Djigma, W.F., Nadembega, C.M., Belemgnegre, M., Ouedraogo, P., Sanou, M., Karou, D.S., Traore, Y. and Simpore, J. (2022) Hepatitis B and C Immunological and Molecular Parameter Analysis in HIV-Positive Patients Undergoing Antiretroviral Therapy at Saint Camille Hospital in Ouagadougou (HOSCO), Burkina Faso. Advances in Infectious Diseases, 12, 20-41. https://doi.org/10.4236/aid.2022.121002 Received: November 10, 2021 Accepted: January 24, 2022 Published: January 27, 2022 D. P. Ilboudo et al. DOI: 10.4236/aid.2022.121002 21 Advances in Infectious Diseases (73.88%) were women. At treatment initiation, the mean age was 40.14 ± 11.84 years. The majority of patients consulted at WHO stage III (51.45%). Clinical suspicion was the most frequent screening circumstance (51.71%). The pathologies frequently reported at the first consultation were diarrhea (28%) and shingles (16%). Body mass index was normal in 50.5% of patients. HIV1 infection was the majority (91.03%). A total of 270 had a CD4 count at treatment initiation. The mean CD4 cell count was 304.17 ± 242.06 cells/μL, and 116 (42.59%) of them had a CD4 ≤ 200 cells/μL. Viral load at treatment initiation was documented in 62 patients (16.35%) and 70.97% of them had a detectable viral load (greater than 1000 copies/mL). The clinical and biological evolution was relatively good in patients after therapeutic initiation. HIV-HBV co-infection was 24.11% and HIV-HCV co-infection was 2.26%. The mortality rate was 3.69%. Conclusion: These results reflect a significant delay in HIV infection diagnosis. Furthermore, hepatitis B and/or C is co-infections that increasingly affect people living with HIV. It also appears that COVID 19 disease has had a strong impact on patient management. Thus, new screening strategies must be implemented to encourage early diagnosis of HIV, hepatitis B and C. Effective strategies are also necessary to fight HIV in the context of epidemics and/or pandemics.


Introduction
Human immunodeficiency Virus (HIV), Hepatitis B virus (HBV), and Hepatitis C virus (HCV), are the three most common chronic viral infections all over the world. They share similar transmission routes including sexual, blood-blood contact, and injecting drug usage [1]. Co-infection with HIV and HCV and/or HBV is very common in certain populations, such as intravenous drug users (IDUs) who often share the contaminated needles/syringes for intravenous drug injection. The rates of HIV-HBV co-infection are reported as high as 10% -20% in countries where HBV infection is either endemic or intermediate to high HBV cases. It has been observed that HBV/HIV co infection leads to increased morbidity and mortality as compared to HIV or HBV mono-infections [2]. The ever increasing burden of these infections has become a growing concern [3].
With increased access to antiretroviral drugs for HIV patients, migrating populations and social networking by intravenous drug use, cases of HBV and HCV co infections have been on the rise [4]. Studies show that HIV co infection adversely impacts on the natural history of HBV and HCV [4] by accelerating progression to chronic liver disease due to drug-related hepatotoxicity and hepatitis reactivation [5] [6]. At this stage, most patients are likely to die due to liv-er-related diseases compared to those without HIV infection [7]. Viral hepatitis is a global health challenge worldwide, particularly in low and middle-income countries [8]. In Africa, hepatitis B virus (HBV) is estimated to affect around 75 million people including 1.9 million in Burkina Faso [9]. The prevalence of HBV and HCV was still high in African countries: in fact, 12.2% HBV prevalence in Nigeria [10]; an overall prevalence of HBsAg of 30.9% in Cote d'Ivoire [11]; and 12.4% in Burkina Faso [12] versus 9.1% [13]. In Senegal prevalence of HBsAg in the general population was 8.1% in 2016 [14]. HCV prevalence is estimated to 2.8% in Kenya, 3.2% in Ghana, 4.9% in Cameroon and, finally, 6.1% in Burkina Faso [15]. The rate of co-infection between HCV and HIV was also high [16].
In short, hepatitis B and C viruses and HIV constitute major problems in the Burkinabé health system [17]. The prevalence of HIV infection in the adult population of Burkina Faso is estimated at 0.70% in 2019 against 0.9% in 2014 and 1% in 2012, with a large predominance of HIV 1 [18]. In practice, studies highlight the impact of these viral infections on the capacity of transfusion blood in the country, HIV 1 is 1% and hepatitis C is 5%. So, viral hepatitis infection is the most common in the country, but it is silent and shows no signs. This implies a particular danger in a country where the prevalence of HIV AIDS is not negligible, these viruses sharing the same routes of contamination as HIV.

Framework of the Study
The study was conducted in the city of Ouagadougou, the political capital of Burkina Faso, and at the Prevention of Mother-to-Child Transmission (PMTCT) unit of the Saint Camille Hospital in Ouagadougou.

Type and Period of Study
This is a descriptive and analytical cross-sectional study with retrospective data collection. It covered the period from 01 st January 2016 to 01 st June 2021. During the study period, 504 patients started antiretroviral treatment in the active file of which 379 patients met the inclusion criteria.

Study Population
A total of 379 patients, whose clinical records were available for the study period were included. Inclusion criteria were HIV1 and/or HIV2 infection and follow-up in the active file of the PMTCT service. Patients transferred to the Day Hospital, under antiretroviral treatment were excluded from the study.

Data Collection Survey
For data collection, a collection form was developed. This data collection consisted of a review of the clinical files of PLHIV who are followed up at the HOSCO and the recording of parameters of interest. We sorted the files concerned for our study and filled out the data collection forms.

Statistical Analysis of Data
Data were entered into Excel 2016 and then analyzed using R software version 4.0.2. Prevalences were calculated with 95% confidence intervals (95% CI). Differences between prevalences, different age groups and CD4 counts, were assessed using Pearson's Chi2 test. The Student Newman test was used for comparison between groups with R software version 4.0.2. Results with p < 0.05 were considered statistically significant.

Ethical Considerations
This study was conducted in the context of routine care. All information collected was kept strictly confidential and patient names were not included in the exported data. The study had the approval of the institutional ethics committee of the HOSCO.

Socio-Demographic Characteristics
The majority of patients were female, with 280 women (73.88%), giving a male/female sex ratio of 0. 35 Non-HIV related history was diabetes and hypertension. Hypertension was a history in 9 patients of whom 8 were on treatment. Also, 3 patients or 0.79% had diabetes and 2 of them were on treatment. The association of hypertension and diabetes was recorded in 1 patient. There was no statistically significant difference (p-value > 0.05) between the initiation of antihypertensive treatment and the initiation of antidiabetic treatment ( Table 2).
2) Circumstances of screening difference between clinical stages was also statistically significant. Table 3 shows also the distribution of patients according to their WHO clinical stage at inclusion.

4) Body mass index (BMI) evolution
BMI was assessed in 303 patients or 79.95% of the population. Before treatment, the mean BMI was 23.14 ± 5.7 kg/m 2 and slightly more than half of the patients or 50.5% had a normal BMI with a significance of results p < 2.2e−16 (Table 3). Compared to data after the treatment, we observed a progressive weight gain of the patients after they started ART ( Figure 1).

5) Evolution of clinical events
The clinical events at ARV treatment initiation were reported in 102 patients or 26.91% of the study population. These clinical events after ART initiation were dominated by diarrhea and herpes zoster with 28% and 16% respectively. These differences were statistically significant at p = 2.56e−08 (Table 4). They changed under treatment. In fact, the number of clinical events decreased during follow-up. Indeed, of the 102 patients presenting a clinical event at the beginning of treatment, only 38 (10.03% of the study population) presented a clinical failure during treatment.

1) Type of HIV
HIV 1 infection was the majority in the study population and concerned 345 patients or 91.03% (345/379) and HIV 2 was 4.22% (16/379). Co-infection between HIV1 and 2 was 4.75% (18/379). The differences between results were highly significant p ≤ 2.2e−16.  2) CD4 evolution after initiation of ARV treatment The initial CD4 quantification was performed for 270 patients. We found 71.24% of the study population at treatment initiation with a mean CD4 count of 304.17 ± 242.06 cells/µL, the extremes ranging from 1 to 1286 cells/µL. The majority of patients (42.59%) had CD4 counts below 200 cells/µL. They gained under treatment. Figure 2 shows the evolution of patients' CD4 lymphocytes according to the duration of treatment. The gain in CD4 was regular in patients after initiation of treatment. The plateau was reached rapidly with stabilization after 12 months of treatment and return to near normal CD4 values. Under treatment, 12.14% of patients experienced immunological failure.

3) Evolution of the viral load after initiation of ARV treatment
The viral load at initiation of therapy was documented in only 62 patients or 16.35% of patients and 70.97% had a detectable viral load (greater than 1000). The differences observed between the viral load groups are statistically significant with p = 0.0103. Notable changes have been noted after treatment and during treatments. Indeed, a large majority of patients (91.25%) who started treatment had an undetectable viral load after 6 months of follow-up compared to 82.76% after 12 months. Virological failure was reported in 11.08% of patients on ARV treatment. The data are shown in Figure 3.

4) Biochemical parameters
Alanine aminotransferase (ALT) value was recorded in 300 (68.60%) patients. The median was 21. UI/l with extremes of 0 and 355.7 and the mean was 28.58 ± 28.83 UI/l. Values were normal in 97.09% of patients. The mean of aspartate aminotransferase (ASAT) was 34.83 ± 28.05 UI/l with extremes of 6.2 and 350.2 UI/l. Blood glucose values were not informed in 40.63% of our patients. The mean was 5.06 ± 2.24 IU mmol/L; and most of our patients, 95.45% had normal blood glucose levels. The mean hemoglobin level at therapeutic initiation was 11.62 ± 1.99 g/dL with extremes ranging from 6 to 17.7 g/dl and a median of   11.6 g/dl; 127 patients (40.32%) were anemic of which only 01 had severe anemia. The mean creatinine clearance was 97.7 ± 27.98 mL/min; 11.08% of the patients had a clearance below normal (90 mL/min).  Table 6 shows the distribution of patients according to their first-line treatment regimen.

8) Patient outcomes
Retention in the active file of the study population was 75.2%. The mortality rate was 3.69%. The following table shows the outcome of the patients included in the study. With a p-value of 2.2e−16 indicating significant differences (Table  7).

Discussion
The present study included 280 women or 73.88% of the total population. This gives an M/F sex and West Africa. Thus, in Benin, Amidou et al. (2018) found 65.1% the same female trend in their study [19]. This female predominance found in the study populations is a reflection of the feminization of HIV infection in Africa where 58% of HIV positive women are found out of the total of sub-Saharan Africa [17]. This feminization of HIV infection in Burkina Faso could be explained by a much higher use of health services by women. This feminization of HIV infection in Burkina Faso could be explained by a much greater use of health services by women. Moreover, Burkina Faso has emphasized PMTCT, which allows many pregnant women to be screened. Also according to the national committee for the fight against HIV, the general population of Burkina Faso is mostly female (51.7%) [18]. In addition, many factors favor women's vulnerability to HIV infection, compared to men who are protected by circumcision, anatomical factors; physiological (the vagina due to its large surface and fragility facilitates the penetration of the virus, as well as the frequency of STIs); socio-cultural factors (sexual activity tends to be early in women and generally with older partners) [17]. This study revealed that the average age of patients was 40.14 ± 11.84 years with extremes of 18 and 81 years. The most represented age groups were 35 -45 years with a frequency of 31.66%. HIV affects the most active portion of the population [18] [19] [20] [21]. Indeed, HIV+ patients' age was from 25 to 52 years with an average of 32.0 ± 7.8 in this study in Burkina Faso [22]. Unemployed patients were the most represented 31.66% and housewives constituted the major (25.65%). The majority of our study population (96.06%), resided in urban areas and only (3.94%) resided in rural areas. Moreover, a large proportion of them (93.93%) were from the city of Ouagadougou where the study was conducted. These results probably reflect the policy of decentralization of care for people living with HIV promoted by Burkina Faso.   However, this prevalence is significantly lower than that of the general population of Burkina Faso. Koné (2016) [22] in Mali and Forbi et al. (2007) [40] in Nigeria noted prevalences of 6.5% and 11.1%. In fact, the rate of hepatitis C serology in our context remains low, which underestimates the prevalences obtained. However, Rockstroh et al. (2005) [43] in Europe found in his study on the influence of Hepatitis C on the progression of HIV infection a much higher prevalence (32.9%). This is due to the fact that injecting drug use, which is one of the main routes of HCV transmission, is still a growing phenomenon in Europe. Also, injecting drug users are much more likely to be screened for hepatitis C than the rest of the population. The probability of HIV/HBV co-infection was 0.29% or 29.9%, comparable to 37.18% probability found by Amona, et al.
(2018) [44] in Congo Brazzaville. The probability of HIV/HCV co-infection and HIV/HBV/HCV triple co-infection was 0% and 0.93% respectively. On the other hand, these probabilities were higher (2.7% and 0.7%) in the study conducted by Tremeau-Bravard (2013) [45] in Nigeria. These low rates found in our study would be explained by the low prevalence rate of hepatitis C in our study; two (2) patients were positive for hepatitis C; which made it difficult to relate the 03 infections.
In this study, we found weight gain in patients after initiation of ART.   [20] and much higher than that of Ilboudo, (2013) (2.2%) [36]. Among these 17.41%, about 7% were lost to view during the years 2020-2021. This can be explained on the one hand by the failure to notify cases of death in the follow-up service which are attached to the lost to sight but also and especially by the epidemic context in COVID 19. Indeed, as collateral victims of this pandemic, people living with HIV (PLHIV) have suffered from the allocation of resources (human, material and financial), initially intended for their care, to the care of coronavirus patients. It would thus be advisable to establish strategies in order to minimize at most the repercussions of the fight against COVID 19 on the care of the HIV PLWHA at the risk of moving further away from the objectives fixed at the horizon 2030 (95-95-95), in order to end the AIDS epidemic.

Conclusion
This study showed that the patients were mostly young, uneducated women. HIV1 was the predominant serotype. The pathologies frequently reported at the first consultation were diarrhoea and herpes zoster, and nearly 43% of the patients had less than 200 CD4/µL, reflecting late screening of the patients and consequently the initiation of late antiretroviral treatment, which could compromise the subsequent prognosis of the infection in these newly treated patients. The clinical and biological evolution was relatively good in the patients after the initiation of treatment. Indeed, weight gain and immune restoration were progressive in the majority. Also, the clinical events decreased during the follow-up; the CD4 gain during the follow-up was regular and the viral load after 06 months of follow-up became undetectable in nearly 92% of the patients. This shows the crucial importance of putting patients who test positive on treatment.
HIV-HBV co-infection was 24.11% and HIV-HCV co-infection was 2.26% above the national prevalence in the general population. Thus, we can affirm that hepatitis B and/or C is co-infections that increasingly affect people living with HIV. In addition, the number of people lost to follow-up has increased considerably in recent years due to the advent of COVID 19.

Recommendations
The results of this study show that it is undeniable that emphasis should be placed on raising awareness of the culture of early detection among the population in order to prevent contamination and improve progress on ART, but also to develop effective strategies for combating HIV in times of other epidemics and/or pandemics. It would also be appropriate to systematically search for HBV and HCV infection when HIV infection is discovered.
facilities and technical assistance. Thank to M. Ambroise Koanda for Statistical analysis.

Author Contributions
Study