Risk Factors for SARS-CoV-2 Among a Cohort of Healthcare Workers in Lebanon.

BACKGROUND: Healthcare workers (HCWs) faced substantial risk of infection during the COVID-19 outbreak. This study aims to determine the prevalence of anti-SARS-CoV-2 antibodies in a cross-sectional sample of HCWs as well as risk factors associated with exposure to SARS-CoV-2. METHODS: The study was conducted between March and May 2021 at the American University of Beirut Medical Center (AUBMC), a tertiary hospital located in Lebanon. Socio-demographic and clinical data, as well as data on exposure, PCR results, PPE adherence, and vaccination status, were collected using an online questionnaire. Sera were also collected to determine seropositivity using commercially available enzyme-linked immunoassay (ELISA) targeting the spike (S) and the nucleocapsid proteins (NCP) of SARS-CoV-2. FINDINGS: Among 92 recruited HCWs, 72.3% received PPE training, more than 70% were adherent to using appropriate PPEs, and around 80% were vaccinated. Nurses in this study population were at higher risk of exposure compared to medical doctors, technicians, and other HCWs. Among the HCWs who performed a PCR test, 28.6% were infected with SARs-CoV-2 with workplace exposure not associated with COVID-19 infection. All vaccinated HCWs were seropositive for anti-S IgG with high titer (≥384 BAU/mL), with a significantly higher median anti-S IgG titer compared to unvaccinated HCWs with previous infection (384 vs. 140.1 BAU/mL; p = .0043). CONCLUSIONS: Our study highlights the importance of implementing strict infection control policies among HCWs and deploying an effective COVID-19 vaccination strategy. More studies are needed in Lebanon to assess risk factors of SARS-CoV-2 exposure in the workplace.

Clinical Characteristics and Serum Cytokines Profiling in Hospitalized COVID-19 Patients in Lebanon.

Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a public health threat worldwide. While the majority of patients recover in 3-4 weeks, complications in severely ill patients, including acute respiratory distress syndrome, cardiac injury, thrombosis, and sepsis, can lead to death. Several biomarkers, in addition to cytokine release syndrome (CRS), have been associated with severe and fatal outcomes in coronavirus disease 2019 (COVID-19) patients. The aim of this study is to assess clinical characteristics and cytokines profiles in hospitalized COVID-19 patients in Lebanon. A total of 51 hospitalized COVID-19 patients were recruited between February 2021 and May 2022. Clinical data and sera were collected at two time points: at hospital presentation (T0) and last collected results during hospitalization (T1). Our results showed that 49% of participants were >60 years with males accounting for the majority (72.5%). Hypertension, followed by diabetes and dyslipidemia, were the most frequent comorbid conditions among study participants accounting for 56.9% and 31.4%, respectively. Chronic obstructive pulmonary disease (COPD) was the only significantly different comorbid condition between intensive care unit (ICU) and non-ICU patients. Our results also showed that the median level of D-dimer was significantly elevated among patients in ICU and those who died compared to non-ICU patients and those who survived. Moreover, C-reactive protein (CRP) levels were significantly higher at T0 compared to T1 in ICU and non-ICU patients. The median level of IL-12p70 was significantly higher in patients >60 years compared to those ≤60 years (p = 0.0209). Our data are in agreement with previous reports suggesting the importance of IL-6, CRP, and IL-12p70 in the assessment of risk of severe disease and mortality.

COVID-19 Infections and Predictors of Sickness Related Absences Among Healthcare Workers: The Experience of a Tertiary Care Center With the COVID-19 Pandemic.

BACKGROUND: Little has been published on predictors of prolonged sick leaves during the COVID-19 pandemic. This study aims to determine the rate of COVID-19 infections among healthcare workers (HCWs) and to identify the predictors of longer sick leave days. METHODS: We identified predictors of longer sick leave using linear regression analysis in a cross-sectional study design. RESULTS: Thirty-three percent of the total workforce contracted COVID-19. On average, HCWs took 12.5 sick leave days after COVID-19 infection. The regression analysis revealed that older employees, nurses, and those who caught COVID-19 earlier in the pandemic were more likely to take longer sick leave. CONCLUSIONS: Age, job position, and month of infection predicted sick leave duration among HCWs in our sample. Results imply that transmission was most likely community-based. Public health interventions should consider these factors when planning for future pandemics.

Response to COVID-19 in Lebanon: update, challenges and lessons learned.

The COVID-19 pandemic remains a public health problem threatening national and global health security. The socio-economic impact of COVID-19 was more severe on developing countries including Lebanon, especially due to the fragile healthcare system, weak surveillance infrastructure and lack of comprehensive emergency preparedness and response plans. Lebanon has been struggling with plethora of challenges at the social, economic, financial, political and healthcare levels prior to the COVID-19 pandemic. The COVID-19 pandemic in Lebanon revealed gaps and challenges across the spectrum of preparedness and response to emergencies. Despite these challenges, the Lebanese response was successful in delaying the steep surge of COVID-19 cases and hospitalisations through imposing strict public health and social measures. The deployment of the national vaccination plan in Lebanon in February 2021 coincided with the reduction in the number of cases and hospitalisation rates. The aim of this manuscript is to advance the epidemiologic evolution of COVID-19 in Lebanon pre- and post-vaccination, the challenges affecting the response and recovery, and the lessons learned.

Genomic surveillance of SARS-CoV-2 in COVID-19 vaccinated healthcare workers in Lebanon.

BACKGROUND: The emergence of SARS-CoV-2 variants including the Delta and Omicron along with waning of vaccine-induced immunity over time contributed to increased rates of breakthrough infection specifically among healthcare workers (HCWs). SARS-CoV-2 genomic surveillance is an important tool for timely detection and characterization of circulating variants as well as monitoring the emergence of new strains. Our study is the first national SARS-CoV-2 genomic surveillance among HCWs in Lebanon. METHODS: We collected 250 nasopharyngeal swabs from HCWs across Lebanon between December 2021 and January 2022. Data on the date of positive PCR, vaccination status, specific occupation, and hospitalization status of participants were collected. Extracted viral RNA from nasopharyngeal swabs was converted to cDNA, library prepped using the coronaHIT method, followed by whole genome sequencing on the Illumina NextSeq 500 platform. RESULTS: A total of 133 (57.1%) samples belonging to the Omicron (BA.1.1) sub-lineage were identified, as well as 44 (18.9%) samples belonging to the BA.1 sub-lineage, 28 (12%) belonging to the BA.2 sub-lineage, and only 15 (6.6%) samples belonging to the Delta variant sub-lineage B.1.617.2. These results show that Lebanon followed the global trend in terms of circulating SARS-CoV-2 variants with Delta rapidly replaced by the Omicron variant. CONCLUSION: This study underscores the importance of continuous genomic surveillance programs in Lebanon for the timely detection and characterization of circulating variants. The latter is critical to guide public health policy making and to timely implement public health interventions.

Trends & predictors of non-AIDS comorbidities among people living with HIV and receiving antiretroviral therapy in Lebanon.

ABSTRACT: Combined antiretroviral therapy (cART) increased the life expectancy of people living with Human Immunodeficiency Virus (HIV) (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. Consequently, PLHIV are experiencing non-acquired immunodeficiency syndrome (AIDS) associated comorbid conditions including diabetes, hyperlipidemia, hypertension, and cardiovascular disease. The aim of this study is to determine the frequency of non-AIDS associated comorbid conditions among a cohort of PLHIV on cART in Lebanon.Data were collected between November 2018 and December 2019 from 105 voluntary participants. A standardized questionnaire was used to collect demographic and behavioral data including lifestyle, smoking, physical activity, substance use and abuse in addition to co-infections and family history of non-communicable diseases. Moreover, data on occurrence and treatment of cardiovascular disease, hypertension, diabetes, lipid and metabolic disorders as well as mental health were collected. Blood samples were used to assess the levels of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1C), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein, total cholesterol, and serum creatinine.Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and cardiovascular disease (9.7%) were mainly reported among study participants. Higher rate of comorbid conditions was observed among participants >40 years of age than those ≤40 years with both hypertension and hyperlipidemia most commonly reported. Older age (odds ratio [OR] 7.6; 95% CI: 1.83-31.98; P = .005) is associated with higher odds of having hyperlipidemia. Moreover, participants on cART for ≥10 years are 5 times more likely to have hyperlipidemia (OR 5; 95% CI: 1.08-22.73; P = .039). Our results also showed that study participants did not experience anxiety, depression or somatic symptoms and that there was no association between these mental disorders and older age or comorbidities.Our results provide important information on HIV trends and associated comorbidities in Lebanon and can be used to improve the management of non-communicable diseases among PLHIV.

Expression of Killer Immunoglobulin Receptor Genes among HIV-Infected Individuals with Non-AIDS Comorbidities.

Combined antiretroviral therapy (cART) increased the life expectancy of people living with HIV (PLHIV) and remarkably reduced the morbidity and mortality associated with HIV infection. However, non-AIDS associated comorbidities including diabetes, hypertension, hyperlipidemia, and cardiovascular diseases (CVD) are increasingly reported among PLHIV receiving cART. Killer cell immunoglobulin receptors (KIRs) expressed on the surface of natural killer (NK) cells have been previously implicated in controlling HIV disease progression. The aim of this study is to investigate the role of KIRs in developing non-AIDS associated comorbidities among PLHIV. Demographic and behavioral data were collected from voluntary participants using a standardized questionnaire. Whole blood samples were collected for KIR genotyping. Hypertension (29.5%) and hyperlipidemia (29.5%) followed by diabetes (23.7%) and CVD (9.7%) were mainly reported among our study participants with higher rate of comorbid conditions observed among participants > 40 years old. The observed KIR frequency (OF) was ≥90% for inhibitory KIR2DL1 and KIR3DL1, activating KIR2DS4 and the pseudogene KIR2DP1 among study participants. We detected significant differences in the expression of KIR3DS4 and KIR3DL1 (p = 0.038) between diabetic and nondiabetic and in the expression of KIR2DL3 between hypertensive and normotensive HIV-infected individuals (p = 0.047). Moreover, KIR2DL1 and KIR2DP1 were associated with significantly reduced odds of having CVD (OR 0.08; 95% CI: 0.01-0.69; p = 0.022). Our study suggests the potential role of KIR in predisposition to non-AIDS comorbidities among PLHIV and underscores the need for more studies to further elucidate the role of KIRs in this population.

The Role of Natural Killer Cells and Regulatory T Cells While Aging with Human Immunodeficiency Virus.

Combined antiretroviral therapy (cART) has increased the quality of life of people living with HIV (PLHIV). Consequently, the number of PLHIV >50 years is increasing worldwide. Patients on cART are known to remain in a proinflammatory state. The latter is linked to the development of non-AIDS-related chronic conditions. Although the number of aging PLHIV is increasing, the effect of HIV infection on the process of aging is not fully understood. Understanding the complexity of aging with HIV by investigating the effect of the latter on different components of the innate and adaptive immune systems is important to reduce the impact of these comorbid conditions and improve the quality of life of PLHIV. The role of killer immunoglobulin receptors (KIRs), expressed on the surface of natural killer (NK) cells, and their human leukocyte antigen (HLA) ligands in the clearance, susceptibility to or disease progression following HIV infection is well established. However, data on the effect of KIR-HLA interaction in aging HIV-infected population and the development of non-AIDS-related comorbid conditions are lacking. Moreover, conflicting data exist on the role of regulatory T cells (Tregs) during HIV infection. The purpose of this review is to advance the current knowledge on the role of NK cells and Tregs while aging with HIV infection.

The epidemiology of Norovirus in the Middle East and North Africa (MENA) region: a systematic review.

Norovirus (NoV) is considered the second leading cause of viral acute gastroenteritis (AGE). To our knowledge, there are no systematic reviews assessing the role of NoV in AGE in the Middle East and North Africa (MENA) region. Consequently, we conducted an extensive systematic literature review on articles studying NoV in the 24 countries of the MENA region during the past 15 years (2000-2015). The methods and reporting were set according to the 2015 PRISMA-P and based on the elements from the international prospective register of systematic reviews (PROSPERO). We retrieved 38 studies meeting our predefined inclusion criteria and were used to extract full data. Studies reporting on NoV were conducted in 15 out of the 24 countries of the region. The reported NoV infection rates in MENA countries ranged between 0.82% and 36.84%. The majority of studies were clinical observational studies assessing NoV rates mainly among children. Participants were recruited from in- and outpatient clinics. NoV infection was reported all year round with with peaks observed mainly during cold months. GII.4 was the predominant genotype detected in stool of participants as reported by 16 out of 25 studies (64%). Overall, there is an increasing recognition of NoV as an important causative agent of AGE across all age groups in the MENA region. Further studies are needed to assess the national and the regional burden of NoV among different age groups, its molecular diversity and seasonal variability.

Update on the epidemiology of rotavirus in the Middle East and North Africa.

Rotavirus (RV) is the leading cause of severe acute gastroenteritis (AGE) worldwide. Consequently, we conducted a systematic literature review on articles studying RV in the 25 countries of the MENA region during the past 15years (2000-2015). The methods and reporting were set according to the 2015 preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) and based on the elements from the international prospective register of systematic reviews (PROSPERO). Our literature search identified 169 studies meeting our predefined inclusion criteria. Studies reporting on RV were conducted in 19 out of the 24 countries of the MENA region. The largest number of studies was reported in Turkey (n=32), Iran (n=31), Saudi Arabia (n=19) and Egypt (n=17). The majority of studies reporting on RV gastroenteritis rates were clinical observational studies. In 115 studies out of 169, RV was reported among in-patients whereas 35 studies reported RV among outpatients. The predominantly reported RV genotype in the region was G1[P8] followed by G2[P4] and G9[P8]. The majority of studies (n=108) were conducted among children less than 5years of age whereas the remaining studies reported on AGE among other age groups and rarely adults. In MENA countries, RV infection was reported all year round with peaks described in cold as well as hot months. This systematic review provides a current update on the epidemiology of RV-associated gastroenteritis in countries of the MENA region and draws attention to the major gaps existing in the continuous monitoring of RV.

Characterization of astrovirus-associated gastroenteritis in hospitalized children under five years of age.

PURPOSE: The aim of this study was to determine the incidence and genetic diversity of astrovirus (AstV) detected in children hospitalized for gastroenteritis (GE). METHODS: A multi-center, hospital-based surveillance study was conducted across Lebanon to investigate the incidence of AstV among diarrheal hospitalizations. Viral RNA was extracted from stool samples collected between 2011 and 2013 from children, below the age of 5years, hospitalized for GE at six medical centers across Lebanon. Demographic and clinical data were collected and analyzed. RNA of eligible samples (n=739) was screened by two AstV-specific PCR assays followed by genotype-specific PCR. Sanger sequencing and phylogenetic analysis were performed for genotypic characterization. RESULTS: Overall, 5.5% (41/739) of rotavirus-negative stool samples collected from hospitalized children <5years old tested positive for AstV infection. AstV infections were detected all year long. Diarrhea, dehydration, vomiting and fever were the most common symptoms associated with AstV infections. Children aged 48-59months had the highest incidence of AstV. Using the Vesikari Scoring System to assess clinical severity, 85.4% of children with AstV had a score>11, indicating severe GE. Genotype-specific PCR identified 22 classical and 4 MLB-like AstV specimens. Further sequencing and phylogenetic analysis of orf1b and orf2 genes revealed that AstV classical 1-3, 5, 6, and 8, MLB-1, VA-1 and -2 genotypes circulated in Lebanon. Recombination between classical AstV strains was detected in several cases as evident by the lack of congruency in the tree topologies of the orf1b and orf2. Two cases of mixed infections between classical and non-classical genotypic strains were recorded. CONCLUSION: High genetic diversity was detected among AstVs in Lebanon. AstVs are associated with 5.5% of non-rotavirus GE-associated hospitalizations in children under five years in Lebanon.

Potential role of killer immunoglobulin receptor genes among individuals vaccinated against hepatitis B virus in Lebanon.

AIM: To explore the role of killer immunoglobulin receptor (KIR) genes in responsiveness or non-responsiveness to vaccination against hepatitis B virus. METHODS: We recruited 101 voluntary participants between March 2010 and December 2011. Sera samples from vaccinated and non-vaccinated participants were tested for the presence of anti-HBs antibodies as a measure of protection against hepatitis B, hepatitis B surface antigen and hepatitis B core antibody as indicators of infection by enzyme-linked immunosorbent assay. KIR gene frequencies were determined by polymerase chain reaction. RESULTS: Sera samples from 99 participants were tested for the levels of anti-HBs as an indicator of protection (≥ 10 mIU/mL) following vaccination as defined by the World Health Organization international reference standard. Among the vaccinated participants, 47% (35/74) had anti-HBs titers above 100 mIU/mL, 22% (16/74) had anti-HBs ranging between 10-100 mIU/mL, and 20% (15/74) had values of less than 10 mIU/mL. We report the lack of significant association between the number of vaccine dosages and the titer of antibodies among our vaccinated participants. The inhibitory KIR2DL1, KIR2DL4, KIR3DL1, KIR3DL2, and KIR3DL were detected in more than 95%, whereas KIR2DL2, KIR2DL3, KIR2DL5 (KR2DL5A and KIR2DL5B) were expressed in 56%, 84% and 42% (25% and 29%) of participants, respectively. The observed frequency of the activating KIR genes ranged between 35% and 55% except for KIR2DS4, detected in 95% of the study participants (40.6% 2DS4*001/002; 82.2% 2DS4*003/007). KIR2DP1 pseudogene was detected in 99% of our participants, whereas KIR3DP*001/02/04 and KIR3DP1*003 had frequencies of 17% and 100%, respectively. No association between the frequency of KIR genes and anti-HBs antibodies was detected. When we compared the frequency of KIR genes between vaccinated individuals with protective antibodies titers and those who lost their protective antibody levels, we did not detect a significant difference. KIR2DL5B was significantly different among different groups of vaccinated participants (group I > 100 mIU/mL, group II 10-100 mIU/mL, group III < 10 mIU/mL and group IV with undetectable levels of protective antibodies). CONCLUSION: To our knowledge, this is the first study screening for the possible role of KIR genes among individuals vaccinated against hepatitis B virus (HBV). Our results can be used to design larger studies to better understand the role of KIR genes in protection against or susceptibility to HBV post vaccination.

Norovirus vaccines: Correlates of protection, challenges and limitations.

Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide. NoVs are classified into 6 different genogroups (GGI- GGVI) based on the viral capsid protein with NoV genogroup II genotype 4 (GII.4) being the predominant strain causing human diseases. Supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment of NoV gastroenteritis. However, the worldwide increased recognition of NoV as an important agent of diarrheal gastroenteritis prompted researchers to focus on establishing preventive strategies conferring long-lasting immunity. This review describes the current status of animal and human vaccine models/studies targeting NoV and addresses the factors hampering the development of a broadly effective vaccine.

Clinical and epidemiological characteristics of norovirus gastroenteritis among hospitalized children in Lebanon.

AIM: To assess the burden of norovirus (NoV) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS: Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software. RESULTS: Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for NoV genogroups I (GI) and II (GII). GII accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GI (0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GI gastroenteritis cases were designated GI.3 and one case as GI.4. GII.4 was predominantly detected in stool of our study participants (68%). We report a JB-15/KOR/2008 GII.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GII.4 Sydney 2012 and Sydney 2012/FRA GII.4 strains. We also report the co-circulation of non-GII.4 genotypes among hospitalized children. Our data show that NoV gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months. CONCLUSION: The majority of NoV-associated viral gastroenteritis cases among our participants are attributable to GII.4, which is compatible with results reported worldwide.

Human immunodeficiency virus and viral hepatitis among high-risk groups: Understanding the knowledge gap in the Middle East and North Africa Region.

AIM: To identify gaps in the existing knowledge on single, dual and triple infections of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) in the Middle East and North Africa (MENA) region among men who have sex with men (MSMs), female sex workers (FSWs), injecting drug users (IDUs) and prisoners. METHODS: We performed an extensive literature search on articles published on the topic in the 25 countries of the MENA region. PubMed database was used as the main search engine. Case reports, case series, qualitative studies, editorials, commentaries, authors' replies and animal studies were excluded. Original articles and reviews dealing with the prevalence of HIV, HBV and HCV and their co-infection were included. Data on population type, sample size, age and markers of infections were extracted from the relevant studies. RESULTS: HIV, HBV and HCV are blood-borne viruses with similar modes of transmission. The categories of people at high risk of acquiring HIV-1, HBV and HCV commonly include: MSMs, FSW and IDUs. It is well established that HIV-positive individuals co-infected with HBV or HCV suffer from liver pathology associated with morbidity and mortality. Moreover, HIV-infected individuals do not respond well to treatment for HBV or HCV and hence are at increased risk of hepatic toxicity. Consequently, co-infection of HIV-positive individuals with HBV and/or HCV is a global health problem of significant magnitude. Our review reveals the paucity of epidemiological data for key populations in many countries of the region. Limited number of studies exists in the MENA region on the status of HIV, HBV and HCV and their co-infections among prisoners, MSMs and FSWs. Evidence support the continued increase of the HIV epidemic among MSMs. In addition to the lack of studies on MSMs and FSWs in the MENA region, our review highlights the lack of data on the practices, characteristics, or the status of HIV infection and viral hepatitis among male sex workers selling or exchanging sex for money. CONCLUSION: The MENA countries are in urgent need of advanced research and strengthening of the data collection systems and reporting practices of these infections among key populations.

The changing pattern of hepatitis A in Lebanese adults.

OBJECTIVE: A shift in the age of hepatitis A virus (HAV) infection from early childhood to adulthood has been observed in many developing countries. This epidemiological shift has been attributed to improved socioeconomic status and sanitary conditions resulting in growing cohorts of susceptible young people and hence an increased risk of HAV outbreaks. The aim of this study was to investigate the evolutionary trend of anti-HAV seroprevalence in Lebanon in a cohort of Lebanese adults. METHODS: This was a cross-sectional study employing a convenience sample (voluntary blood donors) along with secondary data analysis. Sera from 283 healthy blood donors were tested for anti-HAV IgG antibodies. Moreover, we analyzed the national reports of HAV cases published by the Lebanese Ministry of Public Health since 2001. RESULTS: Anti-HAV seropositivity increased steadily from 60% in the younger age group (19-29 years) to 91% in the older age group (50-59 years), leaving the younger group at higher risk of acquiring HAV. The national data show that the number of acute hepatitis A infections is higher in the age groups 5-9 and 10-19 years. CONCLUSION: Our seroprevalence data reveal that young adults are becoming more at risk of acquiring HAV infection. Thus the introduction of hepatitis A vaccine is highly recommended.

Screening for antiretroviral drug resistance among treatment-naive human immunodeficiency virus type 1-infected individuals in Lebanon.

INTRODUCTION: Antiretroviral therapy (ART) has been successful at decreasing the morbidity and mortality associated with human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 drug resistance (HIVDR) among ART-naive patients has been documented to compromise the success of initial therapy. This study was conducted to determine the prevalence of HIVDR mutations among newly diagnosed drug-naive HIV-infected individuals in Lebanon. METHODOLOGY: Plasma samples from 37 newly diagnosed participants at various stages of HIV-1 infection were used to determine HIV-1 RNA viral load, isolate viral RNA, and amplify DNA by RT-PCR. Purified PCR products were used to perform genotypic resistance tests. RESULTS: The prevalence of resistance mutations to nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRT), and protease inhibitors (PI) were 5.4%, 10.8%, and 8%, respectively. The major mutations detected in the study participants conferred resistance to NRTIs and NNRTIs recommended for HIV-1 treatment.  No significant relationship between HIV-1 viral load of participants and the mode of HIV-1 transmission or between the occurrence of HIVDR and the mode of transmission was found. CONCLUSIONS: To our knowledge, this is the first study on HIVDR mutations among newly diagnosed HIV-infected persons in Lebanon. The overall prevalence of HIVDR mutations detected in our study was 16%. Our results are important for evaluating the utility of the standard first-line regimens in use, determining the feasibility of HIVDR testing before the initiation of ART, as well as minimizing the emergence and transmission of HIVDR.

The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8⁺ T cell responses.

It is unclear if HIV-1 variants lose the ability to prime naïve CD8(+) cytotoxic T lymphocytes (CTL) during progressive, untreated infection. We conducted a comprehensive longitudinal analysis of viral evolution and its impact on primary and memory CD8(+) T cell responses pre-seroconversion (SC), post-SC, and during combination antiretroviral therapy (cART). Memory T cell responses targeting autologous virus variants reached a nadir by 8 years post-SC with development of AIDS, followed by a transient enhancement of anti-HIV-1 CTL responses upon initiation of cART. We show broad and high magnitude primary T cell responses to late variants in pre-SC T cells, comparable to primary anti-HIV-1 responses induced in T cells from uninfected persons. Despite evolutionary changes, CD8(+) T cells could still be primed to HIV-1 variants. Hence, vaccination against late, mutated epitopes could be successful in enhancing primary reactivity of T cells for control of the residual reservoir of HIV-1 during cART.