Human papillomavirus positivity and cervical lesions in relation to HIV infection: a comparative assessment in the Cameroonian female population.

Cervical lesions, induced by high-risk oncogenic human papillomavirus (HR-HPV), in the context of HIV remains a global health challenge. We determined the effect of HR-HPV on the development of cervical lesions in women with and without HIV infection. A cross-sectional analytical study was conducted among 257 women living in Cameroon. HIV serology, HR-HPV genotyping and cervico-vaginal smear (CVS) were performed for all participants; among those declared HIV positive, plasma HIV viral load and CD4 count were measured. Statistical analyses were performed using Graph Pad version 6.0; P#x003C;0.05 was considered statistically significant. The mean age of the participants in our study was 37±6.5 years. According to HIV serology, 184 (71.59%) were HIV-positive vs. 73 (28.40%) HIV-negative. Among the HIV-positive women, the median CD4 count was 438 [IQR: 317-597] cells/mm3 and the median viremia was #x003C;40 [IQR: #x003C;40-2318] copies/ml. After successful genotyping, the prevalence of HR-HPV was 36.32% (73/201), with a significantly higher proportion in HIV-infected individuals (41.98% (55/131) vs. 25.71% (18/70); P=0.02; OR=2.1). The overall rate of cervical lesions was 23.34% (60/257), with a non-significantly higher proportion in HIV-infected participants (25.00% (46/184) vs. 19.17% (14/73); P=0.31). Relevantly, the presence of HR-HPV was significantly associated with cervical lesions (P#x003C;0.0001; OR=5.07), with a higher odds of cervical lesion in HIV-positive individuals (P#x003C;0.0001 and OR=5.67) compared to HIV-negative individuals (P=0.03 and OR=3.83). Although oncogenic HPV appears to be an independent factor in the development of cervical lesions, this study reveals higher odds of cervical lesions among HIV/HPV co-infection than in HPV infection alone.

Variability of High-Risk Human Papillomavirus and Associated Factors among Women in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Sub-Saharan Africa (SSA) carries the highest burden of high-risk human papillomavirus (HR-HPV) in the world, driven by, and together with, HIV infection. This systematic review aimed to identify HR-HPV genotypes and their associated factors among women in SSA. METHODS: A systematic review and meta-analysis of studies conducted in SSA on HR-HPV was conducted. Standard electronic databases were searched. R software version 3.6.0 was used for meta-analysis, with p < 0.05 considered statistically significant. RESULTS: We included 28 articles with a total of 22,652 participants. The overall pooled prevalence of HR-HPV genotypes was 55.13%, albeit high heterogeneity between studies. The overall pooled prevalence of HR-HPV genotypes in HIV-positive individuals was 75.51%, compared to 52.97% in HIV-negatives (OR = 4.68 (0.71-30.76)). HPV 16 (18%), 35 (10.12%), 52 (9.98%), 18 (9.7%) and 45 (6.82%) genotypes were the most prevalent. Twelve studies identified the most frequently reported risk factors associated with HR-HPV, with HIV infection (66.66%), multiple sexual partners (41.66%) and young age (41.66%) being the most reported risk factors. CONCLUSIONS: The combined prevalence of HR-HPV genotypes among women in general and HIV-infected women in particular remains high in SSA. The presence of several genotypes not covered by the vaccine is remarkable and suggests the need for revision of current vaccination policies to prevent HR-HPV infections.

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies.

Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1ß) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1ß, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response.

Characterization of oral candidiasis according to antiretroviral treatment status, immunological and virological profiles among HIV infected patients in two health facilities in Yaoundé-Cameroon: a cross-sectional and analytical study.

Introduction: oral candidiasis in HIV-disease generally indicates immune incompetence both among antiretroviral treatment (ART) naive and experienced patients. To optimize oral healthcare among people living with HIV (PLHIV) in sub-Saharan Africa (SSA), we sought to evaluate the type and distribution of oral candidiasis with respect to ART-profile and immuno-virological parameters among PLHIV in the Cameroonian context. Methods: a cross-sectional study was conducted among 163 patients (51 ART-naïve and 112 ART-experienced) residing in Yaoundé, Cameroon, from February through May 2019. Oral candidiasis was assessed, while viral load (VL) and CD4-count were measured on Abbott m2000rt and Cy-flow counter platforms, respectively. Data were analyzed using the Statistical Package for the Social Sciences (SPSS) v.21 with p<0.05 considered statistically significant. Results: in all, 18 cases of two forms of oral candidiasis were identified (13 erythematous and 5 pseudomembranous), with the majority, 27.7% (11/51), observed among ART-naïve patients against 6.3% (7/112) in ART-experienced (p=0.006). With respect to immuno-virological profile, 77.8% (14/18) and 22.2% (4/18) of cases were identified among participants with CD4<200 cells/mm3 and CD4>200 cells/mm3, respectively (p<0.0001). In the light of viral load, the occurrence of oral candidiasis was largely observed among subjects with VL≥1000 copies/ml, 83.3% (15/18), against 16.7% (3/18), with VL<1000 copies/ml, irrespective of the candidiasis form (p<0.0001). Conclusion: among PLHIV, erythematous and pseudomembranous candidiasis are commonly found in the absence of ART, driven by immunodeficiency and active viral replication. In spite of the protective role of ART, PLHIV experiencing immuno-virological failure should be referred for management of oral candidiasis.

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

Background: The 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. Methods: A 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™ 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 p<0.05 considered statistically significant. Results: The 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% (≥500 cells/µL) versus 1.8% (200-499 cells/µL), (OR=3.5; p=0.04) and 0.6% (<200 cells/µL), (OR=17.7; p<0.01). According to viral load, SARS-CoV-2 seropositivity was 6.7% (≥40 copies/mL) versus 4.9% (<40 copies/mL), (OR= 3.8; p<0.01). Conclusion: Before 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.

Evaluation of Circulating and Archived HIV-1 Integrase Drug-Resistance Variants among Patients on Third-Line ART in Cameroon: Implications for Dolutegravir-Containing Regimens in Resource-Limited Settings.

To ensure the long-term efficacy of dolutegravir (DTG), we evaluated the genotypic profile in viral reservoirs among patients on third-line (3L) antiretroviral therapy (ART) in Cameroon, according to prior exposure to raltegravir (RAL). A facility-based study was conducted from May through December 2021 among patients on 3L ART from HIV treatment centers in Yaoundé and Douala. Viral load was measured, and genotyping was performed on plasma RNA and proviral DNA. HIV-1 drug resistance mutations were interpreted using HIVdb.v9.1 and phylogeny analysis was performed using MEGA.v7, with P < 0.05 considered significant. Of the 12,093 patients on ART, 53 fully met our inclusion criteria. The median (IQR) age was 51 years (40 to 55 years), and the male/female ratio was 4/5. The median duration on integrase strand-transfer inhibitors (INSTI)-containing regimens was 18 months (12 to 32 months), and 15.09% (8/53) were exposed to RAL. The most administered 3L ART was TDF+3TC+DTG+DRV/r (33.96%, 18/53). Only 5.66% (3/53) had unsuppressed viremia (>1000 copies/mL). Resistance testing in proviral DNA was successful for 18/22 participants and revealed 1/18 patients (5.56%, in the RAL-arm) with archived mutations at major resistance positions (G140R and G163R). Five subtypes were identified, CRF02_AG (12/18), CRF22_01AE (3/18), A1 (1/18), G (1/18), and F2 (1/18). In Cameroon, 3L-experienced patients had a good virological response with a low level of archived mutations in the integrase. This finding underscored the use of DTG-containing ART for heavily treated patients in similar programmatic settings. However, patients with prior exposure to RAL should be closely monitored following a stratified or personalized approach to mitigate risks of INSTI-resistance, alongside pharmacovigilance. IMPORTANCE We described the analysis of the genotypes of the population within third-line antiviral therapy in Cameroon, with a focus on defining the effects of prior raltegravir (RAL) treatment and resistance mutations for current dolutegravir (DTG) treatment. While supporting the current transition to DTG-containing ART in resource-limited settings toward the achievement of the UNAIDS' goal of HIV elimination by 2030, our findings suggested that RAL-exposed patients may need a specific monitoring approach either in a stratified or personalized model of third-line ART to ensure the long-term success of DTG-containing regimens.

High genotypic diversity of human papillomavirus among women in Cameroon: implications for vaccine effectiveness.

Background: The burden of human papillomavirus (HPV) is high in Cameroon, but knowledge on high-risk oncogenic HPV (HR-HPV) is limited. Our study sought to ascertain the HR-HPV genotypes circulating in Cameroon. Methods: A cross-sectional study was conducted among non-vaccinated women in Cameroon. Detection of HR-HPV was performed by real-time PCR on cervico-vaginal swabs. Predictors of HR-HPV were determined following logistic regression analysis, with p < 0.05 considered statistically significant. Results: In total, 364 women were enrolled, with a median age of 41 (34-50) years. Of these, 3.0% were smokers and 26.09% reported having more than three sexual partners. The overall HR-HPV positivity rate was 21.43% (95% CI 17.21-25.64). Predictors of HR-HPV were young age, i.e < 41 years (aOR (95% CI) 0.408 (0.194-0.862); p = 0.018), smoking (aOR 5.199 (1.314-20.575); p = 0.018), and having more than three sex partners (aOR: 2.335 (1.133-4.811); p = 0.022). Overall, 12 HR-HPV genotypes were identified, with 26.98% women coinfected with at least two HR-HPVs, including one case of a triple coinfection. According to to the circulating genotypes, potential vaccine effectiveness was 47% for the 4-valent vaccine and 70% for the 9-valent vaccine. Conclusion: Within the Cameroonian context, at least one out of five women is likely to be an HR-HPV carrier, especially among young people, smokers, and those with multiple sexual partners. Importantly, HR-HPV infection is highly diversified, with vaccine efficacy ranging from about 47% (4-valent) to 70% (9-valent).

Performance of immunochromatographic and immunoenzymatic techniques in the diagnosis of toxoplasmosis in pregnant women in Cameroon: need for harmonization.

Introduction: in order to contribute to the improvement of the management of toxoplasmosis in pregnant women in Cameroon, performance of two techniques commonly used in the diagnosis of toxoplasmosis was evaluated. Methods: a total of 541 pregnant women were recruited from seven hospitals in two Regions of Cameroon, of which 63% (341: Batch1) were from health facilities (HF) using a immunochromatographic technique (ICT) as a screening test for toxoplasmosis, and 37% (200: Batch2) from those using an immunoenzymatic technique (IEZ). On each sample, Ig (Immunoglobulin) G (IgG) and IgM were tested by three techniques: a Rapid Diagnostic Test (RDT), an Enzyme Linked Immuno Sorbent Assay (ELISA) and a Vidas Enzyme-linked fluorescent assay taken as reference (VIDAS/ELFA). The results from the health facilities were recorded. Results: for the IgG assay, our two laboratory methods were sensitive (96.0% and 97.5%) and specific (64.2% and 59.7%). Their concordance rates with the VIDAS/ELFA reference were above 60% (P<0.001). Moreover, for the IgM assay, the performances of the two methods were equivalent: Se= 18.2%, Sp= 99.4% with a low concordance rate (Kappa = 0.24). Considering the results provided by the selected hospitals, the ELISA used in Batch2 showed similar performances to the two techniques used in reference lab while the performances were low for the RDT used in Batch1. Conclusion: both methods showed similar performances (good for (IgG) and poor for IgM). However, for the immunochromatographic method, differences in performance were found between our results and those provided by the selected health facilities. These differences suggest a harmonization of diagnostic techniques for toxoplasmosis in pregnant women in Cameroonian health facilities.

High performance of integrase genotyping on diverse HIV-1 clades circulating in Cameroon: toward a successful transition to dolutegravir-based regimens in low and middle-income countries.

A successful transition to dolutegravir-based regimens in low and middle-income countries (LMICs) requires an integrase genotyping assay effective on diverse HIV-1 clades. We herein developed and validated an in-house integrase genotyping protocol on plasma samples from 195 HIV-infected patients in Cameroon. Median [IQR] viremia was 23,574 (518-109,235) copies/mL; 128/195 participants had ≥1000copies/mL (i.e., WHO-threshold for genotypic resistance testing in LMICs). A total of 18 viral clades were detected: 72(51.1%) CRF02_AG, 38(26.9%) pure subtypes and 31(22.0%) other recombinants. Following WHO-threshold (≥1000copies/ml), sequencing performance was 82.81%(106/128). Regarding viremia, performance was 85.00%(68/80) with ≥100,000copies/mL versus 76.67%(23/30) with 10,000 to 99,999copies/mL (P = 0.22); 83.33%(15/18) with 1,000 to 99,999copies/mL (P = 0.55); 73.68%(14/19) with 500 to 999copies/mL (P = 0.19); 50%(13/26) for 200 to 499copies/mL (P = 0.0005) and 36.36%(8/22) for <200copies/mL (P < 0.0001). The developed in-house integrase-genotyping is highly effective on both pure and recombinant viral clades, even at low-level viremia. This performance underscores its usefulness in monitoring integrase-resistance mutations and supporting the scale-up of dolutegravir-based regimens in LMICs.

Correlation between the immuno-virological response and the nutritional profile of treatment-experienced HIV-infected patients in the East region of Cameroon.

BACKGROUND: HIV management remains concerning and even more challenging in the frame of comorbidities like malnutrition that favors disease progression and mortality in resource-limited settings (RLS). OBJECTIVE: To describe the nutritional parameters of antiretroviral therapy (ART) recipients (without nutritional support) with respect to CD4 count and virological failure. METHODS: A cross-sectional study was conducted from October to December 2018 among 146 consenting participants enrolled in two health facilities of the East-Region of Cameroon. Socio-demographic data, basic clinical information and treatment history were collected; blood samples were collected by venipuncture for laboratory analysis (HIV-1 viral load, CD4 Tcells measurement and biochemical analysis) performed at the "Chantal Biya" International Reference Center", Yaounde, Cameroon. The nutritional profile was assessed by using anthropometric and biochemical parameters. Data were analyzed using Excel 2016, Graph pad prism version 6; Spearman correlation and Kruskal-Wallis test were used; with p<0.05 considered statistically significant. RESULTS: Median [IQR] age was 42 [33-51] years, 76.0% (111/146) were female and median [IQR] duration on ART was 54 [28-86] months. Of these participants, 11.6% (17/146) were underweight based on the body mass index and 4.7% (7/146) were at the stage of advanced weight loss. According to immunovirological responses, 44.5% (65/146) were immunocompromised (CD4<500 cell/µl) and 75.3% (110/146) had an undetectable viremia (<40 copies/mL). CD4 count inversely correlated with total protein concentration (r = -0.18, p = 0.005**). Viremia was inversely correlated with albumin (r = -0.21; p = 0.047*), nutritional risk index (r = -0.28; p = 0.013*), total cholesterol (r = -0.27; p = 0.007**), and positively correlated with total protein (r = 0.27; p<0.001**) concentrations. CONCLUSION: In this RLS, with patients having about five years of ART-experience, malnutrition appears to be driven mainly by a poor BMI, indicating that about one of ten patients falls within this severe condition. However, the largely normal nutritional profiles should be interpreted with caution, considering local realities and food support programs in place. The present outcomes highlight the need for monitoring nutritional status of people receiving ART in RLS, toward the design of optimal food interventions.

Anti-Toxoplasmic Immunoglobulin G Quantitation Correlates with Immunovirological Parameters of HIV-Infected Cameroonians.

BACKGROUND: Toxoplasmosis is still a neglected common opportunistic infection in immunocompromised individuals, who are mainly people living with HIV (PLHIV) in whom reactivation of toxoplasmosis may occur with advanced HIV conditions in resource-limited settings (RLS). OBJECTIVE: The objective was to assess the correlation between anti-toxoplasmic immunoglobulin G (anti-Toxo IgG) concentration and the immuno-virological status of PLHIV. METHODS: A cross-sectional study was conducted in the year 2018 among 100 PLHIV aged ≥18 years in Yaounde-Cameroon. For each participant, anti-Toxo IgG, CD4-T lymphocytes, and plasma viral load (PVL) were measured using ELISA, flow cytometry, and real-time PCR, respectively. RESULTS: Overall, 56% of the participants were seropositive for anti-Toxo IgG, while 33% were negative and 11% were equivocal. All (n=19) those with PVL>1000 copies/mL were seropositive to anti-Toxo IgG versus 52.85% (37/70) with PVL<1000 copies/mL; p<0.0001. Interestingly, all (n=11) those with severe immunodeficiency (T-CD4<200 cells/µL) were positive to anti-Toxo IgG versus 57.69% (45/78) with T-CD4>200 cells/µL; p<0.0001. Most importantly, PVL and anti- Toxo IgG concentration were positively correlated (r = 0.54; p<0.0001), while T-CD4 and anti- Toxo IgG concentration were negatively correlated (r = - 0.70; p<0.0001). Adjusting age, gender, immune status, and virological profile in logistic regression shows that only immune status was independently associated with the serological status of toxoplasmosis (p=0.0004). CONCLUSION: In Cameroon, about half of PLHIV might be seropositive to anti-Toxo IgG, with decreasing immunity appearing as a risk of toxoplasmosis relapse. Thus, in the context of immunodeficiency, routine quantification of anti-Toxo IgG would alleviate the programmatic burden of this opportunistic infection in RLS with the generalized HIV epidemic.

Human immunodeficiency virus is a driven factor of human papilloma virus among women: evidence from a cross-sectional analysis in Yaoundé, Cameroon.

BACKGROUND: Human papillomavirus (HPV) is the leading cause of cervical cancers, causing 270.000 deaths annually worldwide of which 85% occur in developing countries with an increasing risk associated to HIV infection. This study aimed at comparing HPV's positivity and genotype distribution in women according to their HIV status and determinants. METHODS: A comparative study was carried out in 2012 at the Chantal BIYA International Reference Centre (CIRCB) among 278 women enrolled consecutively at the General Hospital and the Gynaeco-Obstetric and Paediatric Hospital of the City of Yaoundé. HPV genotyping was performed by real-time PCR, HIV serological screening by serial algorithm, CD4 T cell phenotyping by flow cytometry and HIV viral load by Abbott m2000RT. Statistical analyses were performed using Microsoft Excel 2016 and Graph Pad version 6.0 software; with P < 0.05 considered statistically significant. RESULTS: Globally, mean age was 37 ± 3 years; median CD4-count for HIV+ was 414 cells/mm3 [IQR: 264.75-588] and median viremia was 50 RNA copies/mL [IQR: < 40-8288]. Overall HPV rate was 38.49% (107/278); 58.88% for single women vs. others (28.97% married, 2.80% divorced, 9.34% for widows), OR: 2.164; p = 0.0319. Following HIV status, HPV rate was 43.48% (80/184) among HIV+ vs. 28.72% (27/94) among HIV- (OR: 1.937; p < 0.0142); HPV genotypes among HIV+ vs. HIV- were respectively distributed as follows: genotype 16 (3.75% vs. 0.00%, p = 0.57), genotype 18 (3.75% vs. 3.70%, p = 1.00), co-infection 16 and others (8.75% vs. 7.40%, p = 1.00), co-infection 18 and others (8.75% vs. 11.11%, p = 0.71), co-infection 16, 18 and others (2.50% vs. 0.00%, p = 1.00) and other genotypes (72.50% vs. 77.78%, p = 0.80). Among HIV+ participants, HPV rate following CD4 was 62.88% (61/97) for CD4 < 500 vs. 35.71% (20/56) for CD4 ≥ 500 (OR: 3.05; p = 0.0012) while HPV rate following HIV viremia was 42.71% (41/96) with < 1000 RNA copies/ml vs. 66.00% (33/50) with > 1000 RNA copies/ml (OR = 0.384; p = 0.009). CONCLUSION: In Yaoundé, HPV rate appear to be very high, with higher rates of genotypes other than 16 and 18. In the event of HIV infection, the risk of HPV positivity is two times higher, favoured essentially by immunodeficiency. Thus, HIV-infected women should be closely monitored to prevent the emergence of cervical cancer.