HIV-1 Gag gene mutations, treatment response and drug resistance to protease inhibitors: a systematic review and meta-analysis protocol

Background: Some mutations in the HIV-1 Gag gene are known to confer resistance to ritonavir-boosted protease inhibitors (PI/r), but their clinical implications remain controversial. This review aims at summarizing current knowledge on HIV-1 Gag gene mutations that are selected under PI/r pressure and their distribution according to viral subtypes. Materials and methods: Randomized and non-randomized trials, cohort and cross-sectional studies evaluating HIV-1 Gag gene mutations and protease resistance associated mutations, will all be included. Searches will be conducted (from January 2000 onwards) in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Latin American and Caribbean Health Sciences Literature (LILAC), Web of Science, African Journals Online, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. Hand searching of the reference lists of relevant reviews and trials will be conducted and we will also look for conference abstracts. Genotypic profiles of both Gag gene and the protease region as well as viral subtypes (especially B vs. non B) will all serve as comparators. Primary outcomes will be the "prevalence of Gag mutations" and the "prevalence of PI/r resistance associated mutations". Secondary outcomes will be the "rate of treatment failure" and the distribution of Gag mutations according to subtypes. Two reviewers will independently screen titles and abstracts, assess the full texts for eligibility, and extract data. If data permits, random effects models will be used where appropriate. This study will be reported according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. Discussion: This systematic review will help identify HIV-1 Gag gene mutations associated to PI/r-based regimen according to viral subtypes. Findings of this review will help to better understand the implications of the Gag gene mutations in PI/r treatment failure. This may later justify considerations of Gag-genotyping within HIV drug resistance interpretation algorithms in the clinical management of patients receiving PI/r regimens. Systematic review registration: PROSPERO: CRD42019114851

Baseline integrase drug resistance mutations and conserved regions across HIV-1 clades in Cameroon: implications for transition to dolutegravir in resource-limited settings

Background: Transition to dolutegravir-based regimens in resource-limited settings (RLS) requires prior understanding of HIV-1 integrase variants and conserved regions. Therefore, we evaluated integrase drug resistance mutations (DRMs) and conserved regions amongst integrase strand transfer inhibitor (INSTI)-naive patients harbouring diverse HIV-1 clades in Cameroon. Methods: A cross-sectional study was conducted amongst 918 INSTI-naive patients from Cameroon (89 ART-naive and 829 ART-experienced patients). HIV-1 sequences were interpreted regarding INSTI-DRMs using the Stanford HIVdb v8.9-1 and the 2019 IAS-USA list. Amino acid positions with <1% variability were considered as highly conserved. Subtyping was performed by phylogeny. Results: Overall prevalence (95% CI) of INSTI-DRMs was 0.8% (0.4-1.7), with 0.0% (0.0-4.0) amongst ART-naive versus 0.9% (0.5-1.9) amongst ART-experienced patients; P = 0.44. Accessory mutations (95% CI) were found in 33.8% (30.9-37.0), with 38.2% (28.1-49.1) amongst ART-naive versus 33.4% (30.4-36.7) amongst ART-experienced patients; P = 0.21. Of 288 HIV-1 integrase amino acid positions, 58.3% were highly conserved across subtypes in the following major regions: V75-G82, E85-P90, H114-G118, K127-W132, E138-G149, Q168-L172, T174-V180, W235-A239 and L241-D253. Wide genetic diversity was found (37 clades), including groups M (92.3%), N (1.4%), O (6.2%) and P (0.1%). Amongst group M, CRF02_AG was predominant (47.4%), with a significantly higher frequency (95% CI) of accessory mutations compared with non-AG [41.4% (36.8-46.0) versus 27.1% (23.3-31.2) respectively; P < 0.001]. Conclusions: The low baseline of INSTI-DRMs (<1%) in Cameroon suggests effectiveness of dolutegravir-based regimens. In spite of high conservation across clades, the variability of accessory mutations between major circulating strains underscores the need for monitoring the selection of INSTI-DRMs while scaling up dolutegravir-based regimens in RLS

po 8397 viral suppression among cameroonian adults adolescents and children receiving antiretroviral therapy in the test treat era

BackgroundGlobal efforts in meeting the 90–90–90 targets reveal that 70% of infected people know their HIV status, 77% of these are receiving antiretroviral therapy (ART) and 82% of treated patients have viral suppression. Since launching the 'test and treat' strategy and wider access to drugs that bring down the viral load (VL), evaluating viral suppression would help to identify those requiring interventions and to make progress towards meeting the targets in Cameroon.MethodsA study was conducted from October 2015 to August 2017 amongst adults (≥20 years), adolescents (10–19) and children (0–9) at 12, 24, 36 and ≥48 months on ART, monitored at the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB) in Yaoundé, Cameroon. VL was established using Abbott m2000RT-PCR. VS was defined as VL <1000 copies/ml; with p<0,05 considered significant.ResultsA total of 1979 patients (70% female) were enrolled (1825 adults, 112 adolescents, 42 children); 1865 were on first-line (NNRTI-based, duration: 48 [IQR 24–48] months) vs. 114 on second-line (PI/r-based, duration: 48 [IQR 36–48] months); with 19%(368) at Month2, 14%(274) at Month24, 10%(207) at Month36% and 54% (1130) at ≥Month48. Overall, viral suppression was 79.4%, and 64.3% had controlled viral replication (VL <40). On first-line, viral suppression was 79.7% (1487) vs. 72.2%(83) on second-line (p=0,076). By ART duration, viral suppression was 83.4%(Month12), 85.8%(Month24), 74.9%(Month36) and 77.3% (≥Month48); p=0,0011. By age-range, viral suppression was 76.2% in children, 54.5% in adolescents, and 80.9% in adults (p<0,0001). By age and ART-regimen, viral suppression on first vs. second line was: children 76.5% vs. 60%; adolescents 51.7% vs. 65.2%; and adults 81.2% vs. 74.7%.ConclusionAbout 80% of Cameroonian patients might be experiencing viral suppression, with a declining performance at adolescence and by 3 years of ART experience. Thus, meeting the viral suppression target by 2020 requires a closer VL monitoring strategy and an adapted adherence support mechanism for adolescents living with HIV in resource-limited settings sharing similar challenges

Pre-existing immunity to SARS-CoV-2 before the COVID-19 pandemic era in Cameroon: A comparative analysis according to HIV-status

BackgroundThe lower burden of COVID-19 in tropical settings may be due to preexisting cross-immunity, which might vary according to geographical locations and potential exposure to other pathogens. We sought to assess the overall prevalence of SARS-CoV-2 antibodies and determine SARS-CoV-2 seropositivity according to HIV-status before the COVID-19 pandemic era. MethodsA cross-sectional and comparative study was conducted at the Chantal BIYA International Reference Centre (CIRCB) on 288 stored plasma samples (163 HIV-positive versus 125 HIV-negative); all collected in 2017-2018, before the COVID-19 pandemic era. Abbott Panbio (TM) COVID-19 IgG/IgM assay was used for detecting SARS-CoV-2 immunoglobulin G (IgG) and M (IgM). Among people living with HIV (PLHIV), HIV-1 viral load and TCD4 cell count (LTCD4) were measured using Abbott Real Time PCR and BD FACSCalibur respectively. Statistical analyses were performed, with pResultsThe median [IQR] age was 25 [15-38] years. Overall seropositivity to SARS-CoV-2 antibodies was 13.5% (39/288) of which 7.3% (21) was IgG, 7.3% (21) IgM and 1.0% (3) IgG/IgM. According to HIV-status in the study population, SARS-CoV-2 seropositivity was 11.0% (18/163) among HIV-positive versus 16.8% (21/125) among HIV-negative respectively, p=0.21. Specifically, IgG was 6.1% (10/163) versus 8.8% (11/125), p=0.26; IgM was 5.5% (9/163) versus 9.6%, (12/125), p=0.13 and IgG/IgM was 0.6% (1/163) versus 1.6% (2/125) respectively. Among PLHIV, SARS-CoV-2 seropositivity according to CD4 count was 9.2% (&gt;= 500 cells/mu L) versus 1.8% (200-499 cells/mu L), (OR=3.5; p=0.04) and 0.6% (&lt;200 cells/mu L), (OR=17.7; p&lt;0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (&gt;= 40 copies/mL) versus 4.9% (&lt;40 copies/mL), (OR= 3.8; p&lt;0.01). ConclusionBefore COVID-19 in Cameroon, cross-reactive antibodies to SARS-CoV-2 were in circulation, indicating COVID-19 preexisting immunity. This preexisting immunity may contribute in attenuating disease severity in tropical settings like Cameroon. Of relevance, COVID-19 preexisting immunity is lower with HIV-infection, specifically with viral replication and poor CD4-cell count. As poor CD4-count leads to lower cross-reactive antibodies (regardless of viral load), people living with HIV appear more vulnerable to COVID-19 and should be prioritized for vaccination

Lipid peroxidation and total cholesterol in HAART-naïve patients infected with circulating recombinant forms of human immunodeficiency virus type-1 in Cameroon.

BackgroundHIV infection has commonly been found to affect lipid profile and antioxidant defense.ObjectivesTo determine the effects of Human Immunodeficiency Virus (HIV) infection and viral subtype on patient's cholesterol and oxidative stress markers, and determine whether in the absence of Highly Active Antiretroviral Therapy (HAART), these biochemical parameters could be useful in patient's management and monitoring disease progression in Cameroon. For this purpose, we measured total cholesterol (TC), LDL cholesterol (LDLC), HDL cholesterol (HDLC), total antioxidant ability (TAA), lipid peroxidation indices (LPI), and malondialdehyde (MDA) in HIV negative persons and HIV positive HAART-naïve patients infected with HIV-1 group M subtypes.MethodsWe measured serum TC, LDLC, HDLC, plasma MDA, and TAA concentrations, and calculated LPI indices in 151 HIV-positive HAART-naïve patients and 134 seronegative controls. We also performed gene sequence analysis on samples from 30 patients to determine the effect of viral genotypes on these biochemical parameters. We also determined the correlation between CD4 cell count and the above biochemical parameters.ResultsWe obtained the following controls/patients values for TC (1.96±0.54/1. 12±0. 48 g/l), LDLC (0. 67±0. 46/0. 43±0. 36 g/l), HDLC (105. 51±28. 10/46. 54±23. 36 mg/dl) TAA (0. 63±0. 17/0. 16±0. 16 mM), MDA (0. 20±0. 07/0. 41±0. 10 µM) and LPI (0. 34±0. 14/26. 02±74. 40). In each case, the difference between the controls and patients was statistically significant (pConclusionThese results show that HIV infection in Cameroon is associated with significant decrease in TAA, LDLC, HDLC and TC, and increased MDA concentration and LPI indices which seem to be linked to the severity of HIV infection as assessed by CD4 cell count. The data suggests increased oxidative stress and lipid peroxidation in HIV-infected patients in Cameroon, and an influence of CRFs on TC and MDA levels

Data collection tool.

(PDF)</p

Standard algortihm for routine COVID-19 testing in Cameroon.

COVID-19: Coronavirus Disease 2019.</p

Study information sheet.

(PDF)</p

Biochemical parameters in HIV-infected patients, correlated with CD4 using Pearson correlation coefficient.

*<p>Significant Pearson correlation (P<0, 05 at a bilateral level).</p>**<p>Significant Pearson correlation (p<0, 01 at a bilateral level).</p

Distribution of HIV-1 subtypes in patients by sex and CD₄ cell counts.

<p>Distribution of HIV-1 subtypes in patients by sex and CD₄ cell counts.</p