|Year : 2019 | Volume
| Issue : 2 | Page : 113-117
Risk factors associated with unsuppressed viral load in HIV-1 infected patients at the first antiretroviral therapy in Morocco
Titou Hicham1, Elkassimi Ilyas2, Hanafi Tarik1, Baba Noureddine1, Boudi Omar1, Frikh Rachid1, Hjira Naoufal1, Boui Mohammed1
1 Department of Dermatology and Venereology, Military Hospital Mohammed V, Mohammed V University, Rabat, Morocco
2 Department of Internal Medicine, Military Hospital Mohammed V, Mohammed V University, Rabat, Morocco
|Date of Web Publication||14-Jun-2019|
Department of Dermatology and Venereology, Military Hospital Mohammed V, Hay Ryad, 10100 Rabat
Source of Support: None, Conflict of Interest: None
Background: Nonsuppression of viral load (VL) in HIV-infected patients on antiretroviral therapy (ART) is associated with increased HIV transmission and poor survival. The objective of this work was to evaluate the factors associated with the unsuppressed VL (VL >400 copies/ml) in HIV-1-infected patients after 6 months of the first-line ART. Methods: This was a retrospective cohort study of 181 patients living with HIV-1 on ART in Dermatology and Venereology Department of Mohamed V Military Teaching Hospital of Rabat, during the period between January 1, 2007, and January 1, 2017. Associated factors were identified through a logistic regression model. Results: Of the 181 patients, 76% were men. At inclusion, the median age was 35 years. Five variables (male sex, initial fasting glucose >1.1 g/l, alcoholism, smoking, and initial VL >10,000 copies/ml) were significantly associated (P < 0.05) with unsuppressed VL. In multivariate analysis, smoking (relative risk [RR]: 4.27, 95% confidence interval [CI]: 1.67–10.89) and initial VL >10,000 (RR: 9.78, 95% CI: 2.40–39.73) were associated independently with unsuppressed VL. Conclusion: Approximately 83% of the patients in the cohort had been able to suppress VL after 6 months of the first-line ART. Smoking and high initial VL were independent risk factors of unsuppressed VL. This work highlights the importance of developing and evaluating targeted interventions for patients at risk of unsuppressed VL on ART.
Keywords: AIDS, antiretroviral therapy, HIV, Morocco, viral load
|How to cite this article:|
Hicham T, Ilyas E, Tarik H, Noureddine B, Omar B, Rachid F, Naoufal H, Mohammed B. Risk factors associated with unsuppressed viral load in HIV-1 infected patients at the first antiretroviral therapy in Morocco. Int J Mycobacteriol 2019;8:113-7
|How to cite this URL:|
Hicham T, Ilyas E, Tarik H, Noureddine B, Omar B, Rachid F, Naoufal H, Mohammed B. Risk factors associated with unsuppressed viral load in HIV-1 infected patients at the first antiretroviral therapy in Morocco. Int J Mycobacteriol [serial online] 2019 [cited 2020 Jan 25];8:113-7. Available from: http://www.ijmyco.org/text.asp?2019/8/2/113/260376
| Introduction|| |
Morocco HIV prevalence remains low in the general population of about 0.1%. The 2016 UNAIDS report estimates the number of people living with HIV/AIDS in Morocco at 22,000, of whom 48% had access to antiretroviral therapy (ART). Since 2010, new HIV infections have decreased by 2% and AIDS-related deaths have decreased by 42%. Contrarywise, in the Middle East and North Africa, the number of AIDS-related deaths increased by 19% during the same period. The HIV infections incidence decline and the proportion increase of patients on ART in Morocco have led to a decrease in HIV-related morbidity and mortality. The new 2017–2021 National Strategic Plan commits Morocco to accelerate the response to HIV. The plan aims to reduce new HIV infections among key and vulnerable populations, eliminate maternal-fetal HIV transmission, reduce HIV-related mortality, combat discrimination, and strengthen governance for effective response. Among the constraints to this program is the management of the growing number of patients with the first-line ART failure., Approximately 14% of patients on the first-line ART experience virologic failure, defined as failure to achieve or maintain suppression of viral replication at HIV RNA level <400 copies/ml., However, only 2% of people currently on ART are on the second-line therapy. The persistence of virologic failure can lead to a rapid decline in health, death, increased risk of HIV transmission, and the risk of selection and accumulation of drug resistance mutations.,,
The World Health Organization (WHO) recommends monitoring viral load (VL) as a preferred approach to immunological and clinical supervision to obtain early and more accurate ART failure indications and switch to second-line therapy. For this purpose, the WHO recommends systematic monitoring of VL after 6 months of ART and at least every 12 months.
The optimal threshold to define virologic failure and to change ART regimens is not established yet. The WHO defines virologic failure as a plasma VL >1000 copies/ml, based on two consecutive VL measurements after 3 months, with support for therapeutic compliance. In patients with unsuppressed VL (e.g., >400 copies/ml), the WHO guidelines recommend adherence counseling and testing repetition. To our knowledge, this is the first study in the Maghreb regarding the factors associated with unsuppressed VL after 6 months of the first-line ART in HIV-1-positive patients. Factors such as young age, male sex, TB/HIV coinfection, high initial CD4 count, previous antiretroviral exposure, and social isolation were cited as associated with the risk of virologic failure under the first-line ART.,,
The objective of our study was to determine the factors associated with unsuppressed VL (VL >400 copies/ml) after 6 months of ART in HIV-1-positive patients.
| Methods|| |
This was an analytical study conducted on a monocentric retrospective cohort. The study population consists of all patients infected with HIV type 1 and followed in the Dermatology–Venerology Department of Mohamed V Military Teaching Hospital, from January 2007 to January 2017. This reference department ensures care and monitoring of HIV-positive military personnel and their families in Morocco. In this study, the inclusion criteria were age ≥18 years, the presence of VL before and after 6 months of ART, the existence of a clinical examination recorded in the chart, and the presence of HIV-1-positive serology confirmed by the western blot or PCR.
Patients who did not have VL results in their medical records or were transferred to another health center or patients who died within 6 months of starting ART were excluded from the statistical analysis. A total of 195 people living with HIV (PLHIV) were identified, of which 14 (or 7%) were excluded.
The first-line treatments received were AZT (or TDF) +3TC + EFV (or IDV).
The following variables were collected by a single investigator: duration under ART, sociodemographic characteristics (age, sex, education level, and marital status), clinical data (therapeutic protocol, Centers for Disease Control and Prevention [CDC] clinical stage, history of tuberculosis, and history of HBV), toxic habits (smoking and alcoholism), anthropometric data (weight and height), and biological data (CD4 count, VL, hemoglobin, and blood glucose). In this study, unsuppressed VL was defined by the presence of a VL >400 copies/ml after 6 months of the first-line ART. The objective of the present study was to compare patients with unsuppressed VL after 6 months of ART (first-line) with those who had a VL <400 copies/ml after the same duration of ART to determine the factors associated with nonsuppression of VL.
The statistical analysis was done by Statistical Package for the Social Sciences version 18.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). Student's t-test was used to compare the continuous variables and the Chi-square test to compare the proportions between the two groups. A multivariate logistic regression analysis was performed to analyze the contribution of different variables. The candidate variables introduced into the model were those significant at P < 0.2 thresholds. The selection was made in step-down.
| Results|| |
A total of 181 patients were included in the study, with a male predominance (76%). The median age at the start of treatment was 35 (interquartile range [IQR]: 30–42) years. About two-thirds of the patients had started ART between 2006 and 2011 (68%). Regarding marital status, three out of four (72%) lived alone (single, divorced, separated, or widowed) and 28% lived as a couple. About 74% of the patients were still in the CDC A and B clinical stage. The median initial CD4 count was 306/ml (IQR: 136–540) and the most recent median CD4 count was 467 (IQR: 317-661). The median plasma VL was 37,100 (IQR: 5115–144,350), and 26% of the patients had a VL <10,000. Approximately one in ten (10%) patients had an initial body mass index of <18.5 kg/m2. The median duration of the first-line ART was 49 months (IQR: 22–96). Regarding the therapeutic protocol at inclusion, 15% had received a protocol containing indinavir [Table 1].
|Table 1: Epidemiological, clinical, and paraclinical characteristics at inclusion of 181 patients on antiretroviral therapy|
Click here to view
After 6 months of the first-line ART, 16.5% (n = 30) of the patients had a VL of 400 copies/ml. In univariate analysis, five factors were significantly associated with the risk of nonsuppression of VL: male sex (P = 0.01), initial VL >10,000 (P = 0.09), smoking (P = 0.005), alcoholism (P = 0.03), and initial fasting glucose >1.10 g/l (P = 0.03) [Table 2]. In multivariate analysis, smoking (relative risk [RR]: 4.27, 95% confidence interval [CI]: 1.67–10.89) and VL >10,000 (RR: 9.78, 95% CI: 2.40–39.73) were associated significantly at the risk of unsuppressed VL after 6 months of ART [Table 3].
|Table 2: Characteristics of virally suppressed (viral load ≤400) and virally unsuppressed patients after 6 months of antiretroviral therapy (n=181)|
Click here to view
|Table 3: Results of multivariate analysis assessing factors associated with nonsuppression of viral load after 6 months of antiretroviral therapy|
Click here to view
| Discussion|| |
The present study evaluated the factors associated with the nonsuppression of VL in a cohort of 182 HIV-1-infected patients on the first-line ART in Morocco. Our results found that 16.5% of the patients had a VL >400 after 6 months of ART. The independent risk factors associated with nonsuppression of VL were smoking and initial VL >10,000.
In our study, males were associated with a higher risk of not completing viral suppression after 6 months of ART. Several studies have reported a similar result.,,, On the other hand, other studies found no difference by sex.,,, Our results may be explained, in part, by better adherence among women., Women were more likely to visit health centers and start ART than men in resource-limited settings., In our study, the high initial VL (>10,000) was an independent risk factor to nonsuppression of VL. In contrast, the rate of CD4 at ART initiation was not retained among the factors associated with nonviral suppression. Some studies found that high initial VL is a virologic failure predictor., Due to cost and technology constraints, monitoring of plasma VL was not a common practice in resource-limited countries. This explains the lack of this parameter in several studies conducted in Sub-Saharan Africa. According to our results, VL tests could be increasingly important in guiding clinical decisions on the response to ART. Indeed, failure of treatment based solely on clinical and immunological factors may cause some patients to switch to second-line ART at an inappropriate time, which may increase the mortality rate and the risk of drug resistance. In this study, smoking was an independent risk factor to unsuppressed VL. Previous studies have found weaker immunological and virological responses to ART in smokers compared to nonsmokers.,, This can be attributed, on the one hand, to the negative biological effects of smoking on the efficacy of antiretroviral drugs,,, and on the other hand, to poor compliance among HIV-infected smokers.,, However, other studies have not found an association between smoking and the immunological and virological responses to ART,,, hence the need for research to investigate the relationship between smoking and markers of HIV infection.
Among the factors selected in this study, alcoholism was found to be associated with unsuppressed VL. Alcohol consumption is common and found in 39%–81% of PLHIV,, which is comparable to our cohort (32%). Some surveys have shown that soldiers under the age of 35 years are more likely to use alcohol than their civilian counterparts. Previous studies have reported a lower immunological and virological responses to ART in PLHIV with excessive alcohol consumption. Indeed, in these patients, stopping alcohol consumption has improved the response to ART.,,, In the literature, alcohol use is associated with poor long-term adherence in PLHIV.,, In our study, initial hyperglycemia (fasting glucose >1.1 g/L) was associated with the nonsuppression of VL. Glucose intolerance and insulin resistance precede weight loss in patients with HIV., Other endocrine abnormalities are associated with HIV infection such as deficiency and resistance to growth hormone, which can also lead to insulin resistance. HIV infection and diabetes require better adherence to achieve therapeutic goals and optimize clinical outcomes. In fact, among PLHIV, chronic disease control is suboptimal and polypharmacy has a negative impact on adherence. HIV-infected patients should be screened for diabetes at the time of diagnosis, at the start of highly active ART (HAART), and 3–6 months after HAART. While some professional organizations advise fasting glucose as a screening tool, the predominant role of insulin resistance in disease development requires that postprandial glucose values, or an oral glucose tolerance test, should be realized.
The results of our study can help to identify groups of patients at risk of virologic failure under ART and allow targeted adherence counseling to improve the therapeutic response and avoid switching to more expensive second-line ART.
This study has certain limitations. The first is related to the retrospective nature and the small size of the sample. On the other hand, this study did not take into account factors such as adherence to treatment.
| Conclusion|| |
In this cohort, approximately 83% of the patients achieved viral suppression after 6 months of ART. Our results identified at-risk groups who did not achieve viral suppression, including men, smokers, alcoholics, patients with initial hyperglycemia, and those with a high initial VL. Targeted interventions for at-risk patients remain very important in preventing virologic failure.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fox MP, Cutsem GV, Giddy J, Maskew M, Keiser O, Prozesky H, et al.
Rates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa. J Acquir Immune Defic Syndr 2012;60:428-37.
Fox MP, Ive P, Long L, Maskew M, Sanne I. High rates of survival, immune reconstitution, and virologic suppression on second-line antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 2010;53:500-6.
Boulle A, Van Cutsem G, Hilderbrand K, Cragg C, Abrahams M, Mathee S, et al.
Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa. AIDS 2010;24:563-72.
Ribaudo H, Lennox J, Currier J, Kuritzkes D, Gulick R, Haubrich R, et al
. Virologic Failure Endpoint Definition in Clinical Trials: Is Using HIV-1 RNA Threshold<200 Copies/mL Better than<50 Copies/mL? An Analysis of ACTG Studies. 16th
Conference on Retro- Viruses and Opportunistic Infections, Montreal, Canada; 8-11 February, 2009.
World Health Organization, UNICEF. Towards Universal Access: Scaling up Priority HIV/AIDS Interventions in the Health Sector – Progress Report, September 2009. Geneva, Switzerland: World Health Organization; 2009.
Mirsaeidi M, Sadikot RT. Patients at high risk of tuberculosis recurrence. Int J Mycobacteriol 2018;7:1-6.
] [Full text]
Azeez A, Ndege J, Mutambayi R. Associated factors with unsuccessful tuberculosis treatment outcomes among tuberculosis/HIV coinfected patients with drug-resistant tuberculosis. Int J Mycobacteriol 2018;7:347-54.
] [Full text]
Rangarajan S, Donn JC, Giang le T, Bui DD, Hung Nguyen H, Tou PB, et al.
Factors associated with HIV viral load suppression on antiretroviral therapy in Vietnam. J Virus Erad 2016;2:94-101.
Nsubuga-Nyombi T, Sensalire S, Karamagi E, Aloyo J, Byabagambi J, Rahimzai M, et al.
Multivariate analysis of covariates of adherence among HIV-positive mothers with low viral suppression. AIDS Res Ther 2018;15:9.
Joseph Davey D, Abrahams Z, Feinberg M, Prins M, Serrao C, Medeossi B, et al.
Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa. Int J STD AIDS 2018;29:603-10.
Datay MI, Boulle A, Mant D, Yudkin P. Associations with virologic treatment failure in adults on antiretroviral therapy in South Africa. J Acquir Immune Defic Syndr 2010;54:489-95.
Floridia M, Giuliano M, Palmisano L, Vella S. Gender differences in the treatment of HIV infection. Pharmacol Res 2008;58:173-82.
Nicastri E, Angeletti C, Palmisano L, Sarmati L, Chiesi A, Geraci A, et al.
Gender differences in clinical progression of HIV-1-infected individuals during long-term highly active antiretroviral therapy. AIDS 2005;19:577-83.
Prins M, Meyer L, Hessol NA. Sex and the course of HIV infection in the pre- and highly active antiretroviral therapy eras. AIDS 2005;19:357-70.
Bastard M, Fall MB; Groupe D'étude de la Cohorte ANRS 1215. Long term adherence to HAART in senegal. Bull Soc Pathol Exot 2014;107:241-3.
Bastard M, Fall MB, Lanièce I, Taverne B, Desclaux A, Ecochard R, et al.
Revisiting long-term adherence to highly active antiretroviral therapy in senegal using latent class analysis. J Acquir Immune Defic Syndr 2011;57:55-61.
Desclaux A, Msellati P, Walentowitz S. Women, mothers and HIV care in resource-poor settings. Soc Sci Med 2009;69:803-6.
Meloni ST, Chang CA, Eisen G, Jolayemi T, Banigbe B, Okonkwo PI. Long-term outcomes on antiretroviral therapy in a large scale-up program in Nigeria. PLoS One 2016;11:e0164030.
Huang P, Tan J, Ma W, Zheng H, Lu Y, Wang N. Outcomes of antiretroviral treatment in HIV-infected adults: A dynamic and observational cohort study in Shenzhen, China, 2003-2014. BMJ Open 2015;5:e007508.
Coetzee D, Hildebrand K, Boulle A, Maartens G, Louis F, Labatala V, et al.
Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. AIDS 2004;18:887-95.
Brown JL, Winhusen T, DiClemente RJ, Sales JM, Rose ES, Safonova P, et al.
The association between cigarette smoking, virologic suppression, and CD4+lymphocyte count in HIV-infected Russian women. AIDS Care 2017;29:1102-6.
Feldman JG, Minkoff H, Schneider MF, Gange SJ, Cohen M, Watts DH, et al.
Association of cigarette smoking with HIV prognosis among women in the HAART era: A report from the women's interagency HIV study. Am J Public Health 2006;96:1060-5.
Wojna V, Robles L, Skolasky RL, Mayo R, Selnes O, de la Torre T, et al.
Associations of cigarette smoking with viral immune and cognitive function in human immunodeficiency virus-seropositive women. J Neurovirol 2007;13:561-8.
Feldman DN, Feldman JG, Greenblatt R, Anastos K, Pearce L, Cohen M, et al.
CYP1A1 genotype modifies the impact of smoking on effectiveness of HAART among women. AIDS Educ Prev 2009;21:81-93.
Higgins N, Zingman BS, Slish J, Reichman RC, Fischl MA, Gripshover B, et al.
Factors associated with altered pharmacokinetics in substance users and non-substance users receiving lopinavir and atazanavir. Am J Addict 2007;16:488-94.
Peretti-Watel P, Spire B, Lert F, Obadia Y; VESPA Group. Drug use patterns and adherence to treatment among HIV-positive patients: Evidence from a large sample of French outpatients (ANRS-EN12-VESPA 2003). Drug Alcohol Depend 2006;82 Suppl 1:S71-9.
Webb MS, Vanable PA, Carey MP, Blair DC. Medication adherence in HIV-infected smokers: The mediating role of depressive symptoms. AIDS Educ Prev 2009;21:94-105.
Akhtar-Khaleel WZ, Cook RL, Shoptaw S, Surkan P, Stall R, Beyth RJ, et al.
Trends and predictors of cigarette smoking among HIV seropositive and seronegative men: The multicenter aids cohort study. AIDS Behav 2016;20:622-32.
Kabali C, Cheng DM, Brooks DR, Bridden C, Horsburgh CR Jr., Samet JH, et al.
Recent cigarette smoking and HIV disease progression: No evidence of an association. AIDS Care 2011;23:947-56.
Monroe AK, Lau B, Mugavero MJ, Mathews WC, Mayer KH, Napravnik S, et al.
Heavy alcohol use is associated with worse retention in HIV care. J Acquir Immune Defic Syndr 2016;73:419-25.
Bilal U, Lau B, Lazo M, McCaul ME, Hutton HE, Sulkowski MS, et al.
Interaction between alcohol consumption patterns, antiretroviral therapy type, and liver fibrosis in persons living with HIV. AIDS Patient Care STDS 2016;30:200-7.
Bray RM, Pemberton MR, Hourani LL, Witt M, Olmsted KL, Brown JM, et al.
Department of Defense survey of health related behaviors among active duty military personnel. Research Triangle Park, NC: RTI International; 2009.
Samet JH, Horton NJ, Traphagen ET, Lyon SM, Freedberg KA. Alcohol consumption and HIV disease progression: Are they related? Alcohol Clin Exp Res 2003;27:862-7.
Justice A, Sullivan L, Fiellin D; Veterans Aging Cohort Study Project Team. HIV/AIDS, comorbidity, and alcohol: Can we make a difference? Alcohol Res Health 2010;33:258-66.
Deiss RG, Mesner O, Agan BK, Ganesan A, Okulicz JF, Bavaro M, et al.
Characterizing the association between alcohol and HIV virologic failure in a military cohort on antiretroviral therapy. Alcohol Clin Exp Res 2016;40:529-35.
Malbergier A, Amaral RA, Cardoso LD. Alcohol dependence and CD4 cell count: Is there a relationship? AIDS Care 2015;27:54-8.
Kalichman SC, Grebler T, Amaral CM, McNerney M, White D, Kalichman MO, et al.
Viral suppression and antiretroviral medication adherence among alcohol using HIV-positive adults. Int J Behav Med 2014;21:811-20.
Fichtenbaum CJ, Hadigan CM, Kotler DP, Pierone G Jr., Sax PE, Steinhart CR, et al
. Treating morphologic and metabolic complications in HIV-infected patients on antiretroviral therapy. A consensus statement of an advisory committee of the international association of physicians in AIDS care. IAPAC Mon 2005;11:38-46.
Mondy K, Overton ET, Grubb J, Tong S, Seyfried W, Powderly W, et al.
Metabolic syndrome in HIV-infected patients from an urban, midwestern US outpatient population. Clin Infect Dis 2007;44:726-34.
Dagogo-Jack S. HIV therapy and diabetes risk. Diabetes Care 2008;31:1267-8.
Adeyemi O, Vibhakar S, Max B. Are we meeting the American Diabetes Association goals for HIV-infected patients with diabetes mellitus? Clin Infect Dis 2009;49:799-802.
Kripalani S, Yao X, Haynes RB. Interventions to enhance medication adherence in chronic medical conditions: A systematic review. Arch Intern Med 2007;167:540-50.
Schambelan M, Benson CA, Carr A, Currier JS, Dubé MP, Gerber JG, et al.
Management of metabolic complications associated with antiretroviral therapy for HIV-1 infection: Recommendations of an international AIDS society-USA panel. J Acquir Immune Defic Syndr 2002;31:257-75.
[Table 1], [Table 2], [Table 3]