Prevalence of Virological Failures in Adult Patients Receiving ARV Treatment at Sikasso Hospital

Introduction: The Human Immunodeficiency Virus (HIV) is the etiological agent of Acquired Immuno deficiency Syndrome (AIDS). Virologic failure is defined as the persistence of a viral load greater than or equal to 1000 copies based on 2 consecutive viral loads 3 months apart, after 6 months of well-conducted treatment. The aim of our study was to estimate the prevalence of virological failures in adult patients on ARV treatment at Sikasso Hospital.

 Material and Methods: This was a 12-month prospective descriptive study from January to December 2016 on adult HIV-1 patients on ARVs at least one (1) year of age who had previously had a plasma viral load in the laboratory department of Sikasso hospital. Viral loads were performed by real-time RT-PCR on Abbott M2000rt with a detection limit of 40 copies/mL. 

Results: We conducted a study on 319 patients, 46.4% of whom were from CERKES, followed by Sikasso Hospital with 33.3%. The prevalence of failure was 27.8% at one year, 19.5% at two years, 12% at three years, and 19.4% at more than three years of antiretroviral treatment. The frequency of undetectable viral load was 57.4% at one year, 74.4% at two years, 84% at three years, and 63% at more than three. Among the patients under Trioday (TDF + 3TC + EFV) the prevalence of virologic failure was 19.5%. In patients taking Duovir-N (AZT + 3TC + NVP) the prevalence of virologic failure was 20.7%. No virological failure has been observed in Tenolam + Kaletra patients (TDF + 3TC + LPV / r). Among patients taking Duovir + Kaletra (AZT + 3TC + LPV / r) the prevalence of virologic failure was 28.7%. 

Conclusion: The proportion of virological failures decreases with increasing duration of ARV treatment.

The human immunodeficiency virus (HIV) is the etiological agent of acquired immunodeficiency syndrome (AIDS). HIV remains a public health problem, the United Nations AIDS Organization (UNAIDS) and the World Health Organization (WHO) indicated in their 2016 annual report that 36.7 million people were living with HIV worldwide, 17 million people on antiretroviral therapy. Sub-Saharan Africa remains the most heavily affected region with 1.4 million people infected, bringing the number of people living with HIV to 26 million. The results of the latest HIV seroprevalence study conducted in 2012/2013 in the general population during the Mali Demographic and Health Survey (EDSMV, 2012-2013), showed a decrease in the HIV prevalence rate from 1.3% to 1.1%. Mali is a country with a generalized HIV epidemic, with low prevalence with a tendency to stabilize. The harmonization of treatment poses enormous problems, the difficulties of access to qualified laboratories, the time taken to return results too long. The SAMBA initiative of Professor Elène LI University of Cambridge who won the inventory of the year award for a simple to use machine the size of a coffee machine, more accessible which allows to obtain the results of the viral load in less than 90 minutes seems to be a good alternative used in Kenya, Uganda, and Malawi. Eradicating the virus throughout the body is extremely difficult, remission is possible. On the other hand, eradicating transmission, rapid diagnosis, treatment, immunovirological monitoring set up during the same trip, plus acceptance of the other are aspects that can lead us to an unexpected result while waiting for the arrival of an effective vaccine. Hence the relevance of the UNAIDS objectives by 2030:

- Zero new infections

- Zero AIDS-related deaths

- Zero discrimination

Virological failure is defined by the persistence of a viral load greater than or equal to 1000 copies based on 2 consecutive viral loads 3 months apart, after 6 months of well-conducted treatment [2]. Many virological markers have been proposed to predict the evolution of HIV infection, but data from several cohort studies have shown that quantification of plasma viral RNA (viral load) was the most relevant marker. The majority of tests used use real-time PCR techniques with a quantification threshold of 40 copies/ml or 10 copies/ml for ultrasensitive techniques [4].

What is the prevalence of virological failures after one (1) year of antiretroviral treatment in Sikasso? The Sikasso region has only one viral load measuring device, namely the Abbott m2000rt. For a region comprising 7 circles and bordering three countries, one of which has a high HIV prevalence, namely Ivory Coast, Burkina Faso, and Guinea Conakry. The Sikasso region combines "factors" favorable to the spread and potentiation of the impact of the epidemic: extreme poverty, illiteracy, especially among women, significant and increasing internal and external migratory flows, risky socio-cultural practices such as levirate and sororate, risky practices at gold mining sites. Added to this are the effects of the socio-political crisis, particularly the displacement of populations fleeing the north of the country [2].

After the expanded access to antiretrovirals, it is therefore important to estimate the prevalence of failures in therapeutic protocols, particularly in Sikasso. Hence the interest of this study.

Objectives

To assess the prevalence of virological failures in adult patients on ARV treatment at Sikasso hospital.

Specific Objectives

To describe the sociodemographic characteristics of patients

To determine the prevalence of virological failures

To detect factors associated with virological failures in patients.

Our study was conducted in the Laboratory-Blood Bank department of Sikasso hospital. This is a prospective descriptive study of 12 months from January to December 2016. Included in our study were all adult patients infected with HIV-1 on ARV for at least one (1) year and having previously had a plasma viral load. Viral loads were performed by real-time RT-PCR on Abbott M2000rt with a detection threshold of 40 copies/ml.

Study parameters

• Age

• Sex

Virological data

• Plasma viral load

Therapeutic data

• Antiretroviral treatment

Ethical aspect

Anonymity and confidentiality of the files were respected.

Technique used

Viral load was performed on "Abbott RealTime HIV-1 Quantitative assay" with ready-to-use kits for the RT-PCR technique.

Our study allowed us to include 319 patients whose viral loads were carried out at the Laboratory department of Sikasso hospital. These patients came from CERKES, USAC of Koutiala, and the hospital's medical department. 50.8% of patients were between 30 and 44 years old. Women were in the majority with a sex ratio of 0.54. In the study population, 60% were married followed by singles with 25%. The most represented socio-professional group was housewives with 41.7% followed by traders with 22%. (Table I).

Table 1: Sociodemographic characteristics

Figure 1: Distribution of patients by gender.

Women were in the majority with a sex ratio of 0.54. (Figure 1)

Figure 2: Distribution of patients according to marital status

In the study population, 60% were married followed by singles with 25%. (Figure 2)

Table 2: Distribution of patients according to the requesting service

The majority of our patients came from CERKES, i.e. 46.4%, followed by Sikasso hospital with 33.3%. (Table II). The regimen comprising 2NRTIs + 1NNRTI was the most observed (94.4%) with 85.3% under Trioday (TDF + 3TC + EFV). The combination of antiretroviral treatment containing 2 NRTIs + 1 IP represented 5.6%. Among patients under first line, 19.6% had virological failure. Among patients under second line, 11.1% had virological failure. Among patients under Trioday, 19.5% had virological failure. Among patients under Duovir-N, 20.7% had virological failure. Under Tenolam + Kaletra, no virological failure was observed in patients. Among patients on Duovir + Kaletra 28.7% had virological failure. (Table III). 70% of patients had an undetectable plasma viral load. 19% of patients had virological failure. Virological failure was estimated at 27.8% in patients with one (1) year of treatment and 19.5% at two (2) years of antiretroviral treatment. At 3 years the virological failure rate was 12% and 19.4

Demographic data

Among the 319 patients included in our study, 18.2% were aged less than or equal to 29 (≤ 29 years), 50.8% were aged between 30-44, and 31% were aged greater than or equal to 45 years (≥45 years). Women represented 64.9% of our study population. Aliou Baldé's thesis found a high prevalence of 68% of women in their studies on virological failures of HIV-1 patients at the CEREFO center at point G [11]. The most represented socio-professional group was housewives with 41.7% followed by traders with 22%. In the study population, 60% were married followed by singles with 25%.

Antiretroviral treatment

94.4% of the 319 patients were on 1st line the regimen comprising 2NRTI + 1NNRTI including Trioday (TDF + 3TC + EFV) largely majority with 85.3% followed by Duovir-N (AZT + 3TC + NVP) with 9.1%. 5.6% were on 2nd line the combination of antiretroviral treatment comprising 2 NRTI + 1PI, Tenolam + Kaletra (TDF + 3TC + LPV / r) with 3.4% and Duovir + Kaletra (AZT + 3TC + LPV / r) with 2.2%. These regimens are in accordance with the new standards and national protocol for antiretroviral management of HIV and AIDS in Mali July 2016. The preferred regimen in first line under first line being Trioday (TDF + 3TC + EFV) which explains this high prevalence.

Plasma viral load

Among the 319 patients, 70% had an undetectable plasma viral load; 11% had a viral load between 40-999 and 19% had virological failure. Our prevalence of virological failure was lower than that of Gora et al. found 56.2% undetectability and a virological failure rate of 31.2% in a study in Dakar on the virological efficacy of antiretroviral treatment by measuring the viral load [13].

In Mali, faced with a viral load between 50 and 1000 copies/ml (Blips* cases of low viral load), the standards and protocols for antiretroviral management of HIV and AIDS July 2016 recommend checking and reinforcing compliance, checking the viral load three months later, if the viral load remains below 1000 copies/ml, maintaining treatment. Viral load and antiretroviral treatment At one year (1 year) of antiretroviral treatment 57.4% of viral loads were undetectable, 14.8% had a viral load between 40-999, and 27.8% were in virological failure. This result is slightly lower than that of Dagnra et al. In Togo who found in patients one year of ARV treatment 30.8% of virological failure [14]. At two years (2 years) of antiretroviral treatment 74.4% of viral loads were undetectable, 6.1% had a viral load between 40-999, and 19.5% were in virological failure. Péré et al. found 28.5% of virological failure in their study in Bangui in the Central African Republic [15]. Leye et al. found in 197 patients at 24 months of treatment in Dakar, Senegal, 10.25% virological failure, which is much lower than ours [16]. At three years (3 years) of antiretroviral treatment, 84% of viral loads were undetectable, 4% had a viral load between 40-999, and 12% were in virological failure. This result is lower than that of the Baldé Thesis with 33.3% virological failure at three years of antiretroviral treatment [11]. At more than three years (>3 years) of antiretroviral treatment, 63% of viral loads were undetectable, 17.6% had a viral load between 40-999, and 19.4% were in virological failure. This result is lower than that of the Baldé Thesis with 33.3% virological failure at more than three years of antiretroviral treatment [11]. Among the patients on first line 19.6% had virological failure. The failure rate among the patients on second line was 11.1%. Among the 272 patients on Trioday (TDF+3TC+EFV) 19.5% had virological failure. Among the 29 patients on Duovir-N (AZT+3TC+NVP) 20.7% had virological failure. Among the 11 patients on Tenolam + Kaletra no virological failure observed. Among the 7 patients on Duovir+Kaletra (AZT+3TC+LPV/r) 28.7% had virological failure.

We conducted a study on 319 HIV-1 infected patients who requested a plasma viral load test after at least one year of treatment and regardless of the treatment regimen (1st line or 2nd line). These patients came mainly from five sites in the Sikasso region (CERKES, Sikasso hospital, USAC Koutiala, Sikasso CS ref, and Kigan CS ref). The prevalence of failures was 27.8% at one year, 19.5% at two years, 12% at three years, and 19.4% at more than three years of antiretroviral treatment. The frequency of undetectable viral load was 57.4% at one year, 74.4% at two years, 84% at three years, and 63% at more than three. Among patients on Trioday (TDF + 3TC + EFV) the prevalence of virological failure was 19.5%. In patients on Duovir-N (AZT + 3TC + NVP) the prevalence of virological failure was 20.7%. No virological failure was observed in patients on Tenolam+Kaletra (TDF+3TC+LPV/r). Among patients on Duovir+Kaletra (AZT+3TC+LPV/r) the prevalence of virological failure was 28.7%. The proportion of virological failures decreases with increasing duration of antiretroviral treatment, i.e. the frequency of undetectable viral load increases with duration of ARV treatment. 

To clinicians

Organize better patient management in terms of biological monitoring

To the Ministry of Health

• Make the means available (human, material and financial resources) for the continuity and popularization of viral load tests and also resistance genotype tests

• Facilitate access to viral load tests for patients at inclusion and under antiretroviral treatment as is done in developed countries to prevent virological failures