Abstract: Although, HIV-2 is generally less pathogenic than HIV-1 and its progression towards AIDS occurs less frequently. HIV-2 remains an important cause of disease in West Africa. This study aimed to evaluate HIV-1 and HIV-2 prevalence among pregnant women and to describe the demographic and clinical profile of patients with HIV-2 infection from 2003-2013 at St Camille and General Lamizana Military Medical Centers. A retrospective investigation was conducted using 12,287 medical records from patients screened for HIV. To respond to the lack of data available regarding HIV-2 treatment and also to address the approach to clinical, biological as well as therapeutic monitoring, 62 HIV-2 infected patients’ medical records were studied. Seroprevalence of 10.6 and 0.14% were obtained, respectively for HIV-1 and HIV-2 among 12,287 women screened during the study period. From the sixty two (62) HIV-2 patients, the average age was 49.2 years (sex ratio was 0.65). The weight loss and diarrhea were the major clinical manifestations observed, respectively 54.8 and 25.8%. Fungi and herpes zoster (shingles) infections were reported as major opportunistic infections. Also, nearly half of the patients had more than 60 kg, less than 2% were in WHO stage IV and about 2/3 had a CD4 count bellow 250 cells mm-3. AZT-3TC-IDV/LPV/R was the most prescribed combination. The gain in weight gain the Body Mass Index (BMI) improvement and the non-significant increase of the rate of CD4 between 1st (M1) and 24th month (M24) were observed after treatment with antiviral.
INTRODUCTION
In 2012, the United Nations Program on HIV/AIDS (UNAIDS), estimated in his global report at 35.3 million the number of people infected with HIV worldwide with, respectively 2.3 million of new infections and 1.6 million deaths each year. Sub-Saharan Africa is so far the most affected region of the world with 25 million infections, followed by South Asia and South East Asia with 4.8 million of cases (UNAIDS., 2013). HIV prevalence in Burkina Faso at the year’s end of 2013 was 1.1% according to World Health Organization (WHO) and UNAIDS. In the country a decrease of the prevalence was observed, from 7.2% in 2001 to 1.1% in 2013. This reduction in prevalance is the result of the efforts made by the gevernment and Non-Government Organizations (NGOs) as well as the awareness of youth regarding HIV/AIDS (Simpore et al., 2007).
However, the number of people living with HIV continues to grow. The number of new infections is higher than the number of deaths (UNAIDS., 2013). The HIV infection persists and remains a public health problem, despite the significant decline in the prevalence in the population. Both types of HIV co-exist in Burkina Faso but with a predominance of HIV-1, 97% of patients (HDS-IV., 2010). A lot of efforts have already been done to reduce the incidence of HIV-1 in Burkina Faso (Pignatelli et al., 2006; Simpore et al., 2006, 2007; Kagone et al., 2011; Linguissi et al., 2012; Foca et al., 2014). On the opposite side, few exertion have been made for HIV-2 because of it has a low virulence and prevalence compare to HIV-1. Most of the reports on HIV-2 are found in West Africa due to the fact that it is highly concentrated in this region, in countries such as Senegal, Nigeria, Ghana, Ivory Coast and Burkina Faso (Ndour et al., 2006; De Mendoza et al., 2014). However, people infected with HIV-2 are subjected to the same opportunistic infections as those people infected with HIV-1. The differences between HIV-1 and HIV-2 lie in their structures (HIV-2 has vrp and vpx proteins while HIV-1 has only vpr) which in turn influence the way the two viruses behave once they enter the human body regarding the treatments, the progression towards AIDS, gene polymorphisms and the resistance to antiretrovirals (De Mendoza et al., 2014).
HIV-2 is also more difficult to monitor than HIV-1 in Burkina Faso, due to the fact that there is no viral load assay available. Infectious samples are shipped in Europe for viral loads and prices are often too high for patients (90% of people live under poverty line with less than 1$ per day). This investigation was undertaken to improve our knowledge on the monitoring of HIV-2 infected patients in Burkina Faso. At first, we estimated the prevalence of HIV-2 and its progression towards AIDS stage in a group of women under treatment, from the Prevention of Mother-to-Child-Transmission program of HIV (PMTCT) at St Camille Medical Center. A dedicated institution to HIV treatment, prevention, research and surveillance. Secondly a systematic review of medical records was performed in order to describe the clinical characteristics of patients infected with HIV-2 as well as the biological and therapeutic procedure used in treatment centers. Finally, the effectiveness of clinical, biological and therapeutic management was assessed over the past ten year (2003-2013).
MATERIALS AND METHODS
A retrospective study was conducted which aimed to describe the evolution in therapeutic drug monitoring of infected patients with HIV-2 through its clinical and biological aspects from June, 2003 to September 2013.
Study design and population: A total of 12,287 pregnant women attending antenatal care were enrolled in the Prevention of Mother-to-Child-Transmission program of HIV (PMTCT) at St Camille medical center (CMSC) from 2003-2013. All of the pregnant women were tested for HIV-1 and HIV-2 antibodies following informed consent, counselling and completion of a questionnaire. Rapid tests were performed to determine serological status of patients according to WHO recommendations. First of all, a primary sensitive test was performed (Determine, Abbott, Chicago, USA). Then, a second specific and differential test was also performed in order to differentiate HIV-1 and HIV-2 (SD Bioline, Standard Diagnosis, Seoul, South Korea). HIV-positive patients underwent a regular clinical and psychological monitoring.
Sampling: Given the low prevalence of HIV-2 and to better assess the efficiency of clinical management of this infection, we have associated to our initial sampling, patients treated at the Military medical Center, General Sangoule Lamizana (CM-GSL). Characteristics such as incomplete charts, untreated, death or loss of follow-up were excluded from our analysis. Out of 77 infected patients with HIV-2, only 80.5% (62/77) were included in this study as follows 29.9% (23/77) at CMSC and 50.6% (39/77) at CM-GSL. Patients’ characteristics such as age, gender, occupation, marital status were recorded. Significant clinical signs were considered for inclusion in the analysis (fever, weight loss, cough, diarrhea, anemia, pruritus, opportunistic infections). The CD4 cells count, hemoglobin level and biochemistry (glycaemia, creatinine, transaminases) parameters were also recorded.
Ethical aspects: This study was approved by the St Camille Medical Center and Ethics Review Committee and the Institutional Review Board of Pietro Annigonni Biomolecular Research Center (CERBA). Patient informed consent was not required as only routine, anonymized, monitoring data were collected and analyzed.
Statistical analysis: Data was analyzed using SPSS 17.0 and Epi Info 3.5.1 softwares. The Chi-square test was used for comparisons. The p-values bellow 0.05 were considered statistically significant.
RESULTS
Data on HIV prevalence: Out of 12,287 pregnant women enrolled in PMTCT of HIV prevention and control programme from 2003-2013 at CMSC, 10.8% (1332/12287) were infected with HIV as follows 10.6% (1302/12287) and 0.14% (17/12287), respectively for HIV-1 and HIV-2 (Table 1). The HIV prevalence lowered significantly from 2003 (19.5%) to 2013 (4.5%) (p< 0.0001, Table 1 and Fig. 1).
| Table 1: | Evolution and distribution of HIV-1/2 among women from 2003 to 2013 |
| *p<0.00001 | |
| Table 2: | Socio-demographic characteristics of infected patients at the time of enrollment in PMTCT |
| PMTCT: Prevention of Mother-to-Child-Transmission program of HIV | |
| Fig. 1: | HIV frequency evolution from 2003-2013 |
Due to the very low prevalence of HIV-2 and in order to obtain a representative cohort statistically significant, HIV-2 infected patients from CM-GSL were added to initial sample.
Socio-demographic and epidemiological characteristics of patients infected with HIV-2: The average age of HIV-2 infected patients was 49.2±8.3, aged from 16 to 68 years. It was noticed a dominance of adult patients aged from 40-55 years with a sex ratio 0.65. Most of the infected women were married (living with a partner) and were housewives, respectively 72.5 and 42% (Table 2).
Clinical, biological and therapeutic data of infected patients at inclusion: The loss of weight as well as diarrhea were the dominant clinical signs at the enrollment of infected patients into the treatment centers of both medical facilities, with respectively 54.8 and 25.8%. Out of 42.6% of opportunistic infections reported, 80.1% were results of combination between fungi infection (Candida sp.) and Herpes zoster.
| Fig. 2: | Overall weights from M1-M24 (M: Month), Weight m1 vs Weight m24, *p<0.046 |
Patients with over 60 kg accounted for 54.8% of the cohort and 1.6% were in stage 4 of WHO (progression from HIV to AIDS). Patients had a weight gain from the 1st month to the 24th month of follow-up (Fig. 2). Furthermore, it was noticed that from the first month of inclusion to the 24th month, patients moved from a thin to a normal state and then from a normal to an overweight state (Fig. 3).
Anemia was present at about 37.1% among patients and 2/3 had CD4 count level below 250 cells mm-3.
| Table 3: | Clinical, biological and therapeutic data of infected patients with HIV-2 |
| BMI: Body mass index, OI: Opportunistic infection | |
| Fig. 3: | BMI M1-M24 |
| Fig. 4: | CD4 count from M1-M24 |
There was an increase in CD4 cell counts from the first month of follow-up to the 24th month (Fig. 4).
The combination, AZT-3TC-IDV was the most prescribed treatment to patients. The changes in the treatment due to the failure of prior treatment used represented 14.5% (Table 3).
DISCUSSION
From 2003-2013, out of the 12,287 pregnant women attending antenatal care at CMSC, 10.8% were detected positive for HIV as follows 97.7, 1.3 and 1.0%, respectively positives for HIV-1, HIV-2 and co-infection HIV-1/2 (Table 1). There is a significant decrease in the distribution of the infected pregnant women with rates of 19.5% in 2003 to 4.8% in 2013 (p<0.0001). Those findings are in agreement with the rate of 2.9% (2.1- 4.0) reported in the National Survey conducted in Ouagadougou among pregnant women (HDS-IV., 2010).
To evaluate efficiently the clinical management of infected patients with HIV-2 as well as factors associated to the progress of the infection towards AIDS stage, we conducted a retrospective study of monitoring of HIV-2 infected patients at CMSC and CM-GSL both located in Ouagadougou, capital city of Burkina Faso.
Over 62 infected patients with HIV-2 were included in the present analysis with an average age of 49.2±0.8 (16-69 years). The sex ratio was 0.67 which is in agreement with the value found in Ivory Coast in the study of (Eholie et al., 1998). Married and housewives patients were represented respectively with 41.9 and 72.5%. Weight loss as well as diarrhea was the most common clinical signs found in more than 54.8% cases studied. The similar values were found in the study among Senegalese women by Ndour et al. (2006). In contrast of the results found in several investigations in the surroundings countries, opportunistic infections and malignancies resulting from depletion of the immune system were presents at a higher rate (42%), essentially fungi infection caused by Candida sp. and Herpes zoster (Ndour et al., 2006; Eholie et al., 1998). At the time of the enrollment in the PMTCT of HIV, 70% of infected patients were treated using the combination of AZT+3TC+IDV/LPV/R. Contrary to several studies conducted in Sub-Saharan Africa most of the patients in our investigation were at a lower stage of HIV infection (I and II) according to WHO. Also, all patients enrolled in the PTMTC of HIV in antenatal care clinics had received medical and social assistance as well as psychological care. The majority of patients were provided with antiretroviral drugs and medical monitoring as soon as the biological parameters of the diseases progression were known. However, we reported 9 changes in the antiretroviral drugs initially prescribed to the patients due to a failure in the treatments (low/unchanged CD4 count, poor health). Several drop-outs of patients were recorded as follows, due to two laboratory errors (cross reaction with HIV-1 and HIV-2), four loss of follow-up, one co-infection with hepatitis B and one unknown reason. In overall it was observed a weight gain from M1 (58.66±15.90) and M 24 (64.46±15.56) (p = 0.046), essentially after a changes in HIV medicines prescribed (Fig. 2). The increase in a weight as well as improvement in Body Mass Index (BMI) appears as good predictors of disease progression. In the Fig. 3 from M1 to M24, BMI is showed as predictor of gain of CD4+T-lymphocyte in women receiving antiretroviral treatment which is in agreement with previous studies (Palermo et al., 2011; Ndour et al., 2006; Matheron et al., 2006). Anti-HIV treatment combined to parameters such as weight gain and BMI will improve the clinical management in low income countries. Furthermore, increasing access to viral load testing for HIV-2 as well as HIV-1, will dramatically improve the quality of HIV treatment services in disadvantaged countries (Matheron et al., 2006; Delarue et al., 2013).
CONCLUSION
Due to coordinated actions in HIV prevention and treatment by the government, financial partners and local populations, there is a decrease in HIV prevalence, since 2003. Despite the fact that, clinical and biological parameters such as weight gain and BMI can be used to monitor the progression of the disease among infected patients. Increasing the availability and affordability of viral load testing is fundamental to improve the clinical management of patients infected with HIV-2.
ACKNOWLEDGMENTS
We are grateful to all the participants of this study. We would like to thank the Italian Episcopal Conference (CEI) and the WAEMU (PACER II) for their financial.