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1.
Sci Rep ; 11(1): 7666, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33828220

RESUMEN

Multiple factors, such as immune disruption, prophylactic co-trimoxazole, and antiretroviral therapy, may influence the structure and function of the gut microbiome of children infected with HIV from birth. In order to understand whether HIV infection altered gut microbiome and to relate changes in microbiome structure and function to immune status, virological response and pediatric ART regimens, we characterized the gut microbiome of 87 HIV-infected and 82 non-exposed HIV-negative children from Yaounde, a cosmopolitan city in Cameroon. We found that children living with HIV had significantly lower alpha diversity in their gut microbiome and altered beta diversity that may not be related to CD4+ T cell count or viral load. There was an increased level of Akkermansia and Faecalibacterium genera and decreased level of Escherichia and other Gamma proteobacteria in children infected with HIV, among other differences. We noted an effect of ethnicity/geography on observed gut microbiome composition and that children on ritonavir-boosted protease inhibitor (PI/r)-based ART had gut microbiome composition that diverged more from HIV-negative controls compared to those on non-nucleoside reverse-transcriptase inhibitors-based ART. Further studies investigating the role of this altered gut microbiome in increased disease susceptibility are warranted for individuals who acquired HIV via mother-to-child transmission.

2.
Artículo en Inglés | MEDLINE | ID: mdl-33501504

RESUMEN

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.

3.
BMC Oral Health ; 20(1): 359, 2020 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308188

RESUMEN

BACKGROUND: HIV infection is associated to different oral manifestations (including periodontal diseases), which have decreased with the advent of antiretroviral therapy (ART). Yet, the occurrence of periodontitis is still consistent among patients with HIV living in sub Saharan-Africa, with limited evidence on the driven factors and mitigating measures in these settings. We aimed at evaluating the occurrence of periodontitis and its associated immunological and virological factors in patients with HIV living in Yaoundé, Cameroon. METHODS: We included 165 (44 ART-naïve and 121 ART-experienced) patients > 18 years old attending the Yaoundé Central Hospital and the Chantal BIYA International Reference Centre, from January-April 2018. The periodontal status was assessed by measuring the clinical attachment loss, periodontal pocket depth, plaques index and gingival bleeding index. CD4+/CD8+ cells and viremia were measured using the fluorescence-activated cell sorting method (FACS Calibur) and the Abbott m2000 RT HIV-1 RNA kit respectively. A standard-questionnaire concerning participants' medical records and oral hygiene methods was filled. Data was analyzed and p < 0.05 considered statistically significant. RESULTS: There was a significantly high prevalence of periodontitis in the ART-naïve (53.2%) compared to the ART-experienced group (37.3%), with a twofold increased risk of the ART-naïve population presenting with periodontitis than the ART-experienced population (OR 2.06, p = 0.03). More importantly, ART-naïve, patients with CD4 < 200 cells presented with higher risk of having periodontitis compared to those with higher CD4-values, with a threefold difference (OR 3.21). Worth noting, males presented with a higher risk of having clinical attachment loss (OR 6.07). There was no significant association between the occurrence of periodontitis and the CD8 (p = 0.45) or viremia (p = 0.10). CONCLUSION: In the Cameroonian context, a considerable number of adults infected with HIV suffer from periodontitis regardless of their treatment profile. Nonetheless, ART-naïve patients have a higher risk, indicating the protective role of ART. Interestingly, severely immune-compromised patients and men are vulnerable to periodontitis, thereby highlighting the need for clinicians to refer patients for regular periodontal screening especially male patients and those with low CD4. Such measures could greatly improve the quality of life of the population living with HIV in Cameroon.


Asunto(s)
Infecciones por VIH , Periodontitis , Adolescente , Adulto , Recuento de Linfocito CD4 , Camerún/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Bolsa Periodontal/epidemiología , Periodontitis/epidemiología , Calidad de Vida , Carga Viral
4.
PLoS One ; 15(11): e0241999, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33186360

RESUMEN

BACKGROUND: Syphilis and HIV can be transmitted from pregnant women to their children and they remain a public health problem in Africa. Our study aimed to determine the trends of seroprevalence of HIV/syphilis co-infection and syphilis infection overtime through the national surveillance system in Cameroon and to explore associated risk factors. METHODS: We conducted cross-sectional studies of HIV and syphilis, targeting each year 7000 first antenatal care (ANC-1) attendees at the same sites during the 2009, 2012 and 2017 sentinel surveillance surveys. Pregnant women were enrolled at their ANC-1, sociodemographic and clinical information were collected. HIV and Syphilis test were performed by serial algorithm as per the national guidelines. Trends were assessed for HIV, syphilis and HIV/syphilis by estimating seroprevalence from cross-sectional studies. Associated risk factors were explored using multinomial logistic regression with 4 outcomes: HIV/syphilis co-infection, HIV infection only, syphilis infection only and no infection. RESULTS: Overall, 6 632, 6 521 and 6 859 pregnant women were enrolled in 2009, 2012 and 2017 respectively. In 2017, a total of 3 901 pregnant women enrolled were tested for syphilis. Almost half of them (47.9%) were living in urban area and were aged less than 25 years (44.7%). While HIV epidemic was on a decline (from 7.6% (95% CI: 6.99-8.28) in 2009 to 5.7% (95% CI: 4.93-6.4) in 2017), a huge significant increase of syphilis prevalence was observed (from 0.6% (95% CI:0.40-0.80) in 2009 to 5.7% (95% CI:4.93-6.40) in 2017). Pregnant women residing in rural areas were more likely to be infected with syphilis than those living in the urban area (aOR = 1.8 [95% CI: 1.3-2.4]). Unmarried pregnant women were three time more likely to be infected by HIV/Syphilis Co-infection than married, cohabiting, widow or divorced pregnant women (aOR = 2.8 [95% CI: 1.3-2.4]). Furthermore; living in Northern region was associated with a lower risk of being infected with HIV (aOR = 0.6 [95% CI: 0.5-0.9]) and Syphilis infection (aOR = 0.6 [95% CI: 0.4-0.9]). CONCLUSION: The epidemiological dynamics of syphilis suggests a growing burden of syphilis infection in the general population of Cameroon. Our findings support the fact that while emphasizing strategies to fight HIV, huge efforts should also be made for strategies to prevent and fight syphilis infection especially among HIV positive women, in rural area, and southern regions.

5.
Curr HIV Res ; 2020 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-32885755

RESUMEN

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: Our 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 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% were seropositive for anti-Toxo IgG, when 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 to 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 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 generalized HIV epidemic.

6.
Antimicrob Resist Infect Control ; 9(1): 143, 2020 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-32843050

RESUMEN

BACKGROUND: Sub-Saharan African countries are transitioning to dolutegravir-based regimens, even for patients with extensive previous drug exposure, including first-generation integrase strand-transfer inhibitors (INSTI) such as raltegravir. Such exposure might have implications on cross-resistance to dolutegravir-based antiretroviral therapies (ART). CASE PRESENTATION: We report a 65 years old Cameroonian, previously exposed to raltegravir, and failing on third-line treatment with multi-drug resistance to darunavir/r and dolutegravir. Genotypic resistance testing (GRT) and viral tropism were performed during monitoring time points. The patient initiated ART in August 2007. At the time point of the first (29.04.2010), second (01.12.2017) and third (08.08.2019) GRT, prior ART exposure included 3TC, d4T, NVP and EFV; additionally TDF, DRV/r and RAL; and additionally ABC and DTG respectively. First GRT revealed mutations associated with resistance only to first-generation Non-nucleoside reverse transcriptase inhibitors (NNRTI). Second GRT revealed mutations associated with high-level resistance to all NRTIs, first generation NNRTIs, all ritonavir boosted protease inhibitors (PI/r), and all INSTI, while viral tropism (using geno2pheno) revealed a CCR5-tropic virus with a false positive rate (FPR) of 60.9% suggesting effectiveness of maraviroc (MRV). The third GRT showed high-level resistance to NRTI, NNRTI, all PI and all INSTI, with additional mutations (H221HY for NNRTI and S147G for INSTI), and a CCR5-tropic virus with a slightly reduced FPR (57.0%). Without any locally available active therapeutic option, the patient has been on a maintenance therapy with "DRV/r (600mg x 2/day)+TDF+3TC" and patient/family-centered adherence has been reinforced. Since the first viral load (VL) measurement in 2010, the patient has had 12 VL tests with the VL ranging from 4.97 Log to 6.44 Log copies/mL and the CD4 count never exceeded 200 cells/µL. CONCLUSIONS: As African countries transition to dolutegravir-based regimens, prior raltegravir-exposure may prompt selection (and potential transmission) of dolutegravir-resistance, supporting case surveillance.

7.
PLoS One ; 15(7): e0235958, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32692778

RESUMEN

BACKGROUND: With the scale-up of antiretroviral therapy (ART), pre-treatment drug resistance (PDR) appears ≥10% amongst ART-initiators in many developing countries, including Cameroon. Northwest region-Cameroon having the second epidemiological burden of HIV infection, generating data on PDR in these geographical settings, will enhance evidence-based decision-making. OBJECTIVES: We sought to ascertain levels of PDR and HIV-1 clade dispersal in rural and urban settings, and their potential association with subtype distribution and CD4-staging. METHODS: A cross-sectional study was conducted from February to May 2017 among patients recently diagnosed with HIV-infection and initiating ART at the Bamenda regional Hospital (urban setting) and the Mbingo Baptist hospital (rural setting). Protease and reverse transcriptase sequencing was performed using an in-house protocol and pre-treatment drug resistance mutations were interpreted using Stanford HIVdb.v8.3. Phylogeny was performed for subtype assignation. RESULTS: A total of 61 patient sequences were generated from ART initiators (median age: 37 years old; 57.4% female; median CD4 cell count: 184 [IQR: 35-387] in urban vs. 161 [IQR: 96-322] cells/mm3 in rural). Overall, the level of PDR was 9.8% (6/61). Of note, burden of PDR was almost doubled in urban (12.9% [4/31]) compared to rural setting 6.7% (2/30), p = 0.352). Fifteen (15) PDR mutations were found among four patients the urban settings [6 resistance mutations to NRTIs:[M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] against two (02) mutations found in two patients in the rural setting[2 resistant mutations to NNRTIs: E138A (1) and Y188H (1)]. The rural setting showed more genetic diversity (8 subtypes) than the urban setting (5 subtypes), with CRF02_AG being the most prevalent clade (72.1% [44/61]). Of note, level of PDR was similar between patients infected with CRF02_AG and non-CRF02_AG infected (9.1% [4/44]) vs. 11.8% [2/17]), p = 1.000). Moreover, PDR appeared higher in patients with CD4 cell count <200 cells/mm3 compared to those with CD4 cell count ≥200 cells/mm3 (14.7% [5/34]) vs. 3.7% [1/27]), p = 0.214). CONCLUSIONS: PDR is at a moderate rate in the Northwest region of Cameroon, with higher burden within urban populations. CRF02_AG is the most predominant clade in both urban and rural settings. No effect of HIV molecular epidemiology and CD4-staging on the presence of PDR in patients living in these settings was found. Our findings suggest close monitoring, NNRTI-sparing regimens or sequencing for patients initiating ART, especially in urban settings.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral/genética , Variación Genética/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Carga Viral/efectos de los fármacos , Adulto , Camerún/epidemiología , Estudios Transversales , Femenino , Genotipo , Infecciones por VIH/epidemiología , Infecciones por VIH/genética , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Población Rural , Población Urbana , Carga Viral/genética
8.
Heliyon ; 6(6): e04118, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32566779

RESUMEN

Background: HIV remains a generalised epidemic in Cameroon, with regular sentinel surveillance surveys (SSS) conducted among pregnant women to monitor the epidemiological dynamics, and for strategic policy making. Our main objective was to actualise data on HIV epidemiology, and compare the trends overtime among pregnant women versus data from the general population in Cameroon. Methods: Sentinel surveillance was conducted in 2016 among pregnant women in the 10 regions (60 sites) of Cameroon, targeting 7,000 first antenatal care (ANC-1) attendees (4,000 in urban; 3,000 in rural). HIV testing was done following the serial national algorithm at the National Public Health Laboratory. Results of 2016 were compared with 2009 and 2012 dataset, alongside reports from the general population; with p < 0.05 considered statistical significant. Findings: A total of 6,859 ANC-1 (97.99% sampling) were enrolled in 2016, with 99.19% (6,513/6,566) acceptability for HIV testing; similar to performances in 2009 and 2012 (>99%). National prevalence of HIV was 5.70% (389/6,819), similar between urban (5.58%) and rural (5.87%) settings. HIV prevalence among pregnant women declined significantly from 2009 (7.6%), 2012 (7.8%) to 2016 (5.7%), p < 0.0001; with a similar declining trend in the general population: from 2004 (5.5%), 2011 (4.3%) to 2017 (3.4%), p < 0.0001. Difference between SSS and the population-based survey was non-significant (r = 0.6; p = 0.285). Following geographical settings, HIV prevalence was higher in urban vs. rural settings from 2009-2012 (p < 0.0001), followed by similar rates in 2016. Early-age infection (15-24 years) decreased from 6.7% in 2009 to 3.4% in 2016, with remarkable declines in new infections within the age ranges 15-19 years (5.1%-1.57%) and 20-24 years (7.8%-4.39%). Interpretation: With high acceptability in HIV testing, the prevalence of HIV-infection through SSS indicates a declining but generalised epidemic among pregnant women in Cameroon. Of note, as the declining prevalence among pregnant women also reflects an epidemic reduction in the general population, SSS represents an efficient strategy to understand the dynamics of HIV epidemics in the general Cameroonian population, pending validation by periodic population surveys.

9.
Virol J ; 17(1): 69, 2020 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-32430034

RESUMEN

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.

10.
AIDS Res Ther ; 17(1): 14, 2020 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-32398107

RESUMEN

BACKGROUND: The high rate of mortality among HIV-vertically infected adolescents might be favoured by HIV drug resistance (HIVDR) emergence, which calls for timeous actions in this underserved population. We thus sought to evaluate program quality indicators (PQIs) of HIVDR among HIV-vertically infected adolescents on antiretroviral therapy (ART). METHODS: A study was conducted in the Centre region of Cameroon among adolescents (10-19 years) receiving ART in two urban (The Mother-Child Centre of the Chantal BIYA Foundation, the National Social Welfare Hospital) and three rural (Mfou District Hospital, Mbalmayo District Hospital and Nkomo Medical Center) health facilities. Following an exhaustive sampling from ART registers, patient medical files and pharmacy records, data was abstracted for seven PQIs: on-time drug pick-up; retention in care; pharmacy stock outs; dispensing practices; viral load coverage; viral suppression and adequate switch to second-line. Performance in PQIs was interpreted following the WHO-recommended thresholds (desirable, fair and/or poor); with p < 0.05 considered significant. RESULTS: Among 967 adolescents (888 urban versus 79 rural) registered in the study sites, validated data was available for 633 (554 in urban and 79 in rural). Performance in the urban vs. rural settings was respectively: on-time drug pick-up was significantly poorer in rural (79% vs. 46%, p = 0.00000006); retention in care was fair in urban (80% vs. 72%, p = 0.17); pharmacy stock outs was significantly higher in urban settings (92% vs. 50%, p = 0.004); dispensing practices was desirable (100% vs. 100%, p = 1.000); viral load coverage was desirable only in urban sites (84% vs. 37%, p < 0.0001); viral suppression was poor (33% vs. 53%, p = 0.08); adequate switch to second-line varied (38.1% vs. 100%, p = 0.384). CONCLUSION: Among adolescents on ART in Cameroon, dispensing practices are appropriate, while adherence to ART program and viral load coverage are better in urban settings. However, in both urban and rural settings, pharmacy stock outs, poor viral suppression and inadequate switch to second-line among adolescents require corrective public-health actions to limit HIVDR and to improve transition towards adult care in countries sharing similar programmatic features.

11.
Syst Rev ; 9(1): 93, 2020 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-32334643

RESUMEN

BACKGROUND: Sub-Saharan Africa carries the greatest burden of HIV-infection with increasing drug resistance burden, which requires improved patient management and monitoring. Current WHO recommendations suggest transitioning to dolutegravir-based (adults) or raltegravir-based-regimens (neonates) for initial antiretroviral therapy (ART) and as a suitable alternative in cases of multi-resistance in resource-limited settings. This review aims at synthesizing the current knowledge on dolutegravir use and integrase resistance-associated mutations found before the wide use of dolutegravir-based regimens. METHODS: This systematic review will include randomized and non-randomized trials, cohort, and cross-sectional studies published on dolutegravir use or integrase resistance-associated mutations in Sub-Saharan Africa. Searches will be conducted (from 2007 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. We will include studies of adults and/or children exposed to integrase inhibitors-based therapies; especially dolutegravir or raltegravir (which is our intervention of interest as compared to other antiretroviral regimens). We will exclude studies of patients with specific co-morbidities such as tuberculosis or opportunistic infections. Primary outcomes will be "the rate of viral suppression" and "the level of drug resistance" on integrase inhibitor-based regimens among patients in Sub-Saharan Africa. Secondary outcomes will be "the effect of baseline viremia on viral suppression," "the effect of treatment duration on viral suppression," "the proportion of patients with immune recovery," "the rate of non-adherence," "rate of adverse events;" "drug resistance according to different integrase inhibitor-based regimens," and "drug resistance according to viral subtypes/recombinants." 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. Subgroup and additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., age, sex, baseline viremia, CD4 following treatment, treatment duration, and adherence level). DISCUSSION: This review will help to strengthen evidence on the effectiveness of integrase strand transfer inhibitors by contributing to current knowledge on the use of dolutegravir and/or raltegravir (especially for neonates) in Sub-Saharan Africa. Results will therefore help in setting-up baseline data for an optimal management of people living with HIV as Sub-Saharan African countries are transitioning to dolutegravir-based regimens. Evidence will also support HIV/AIDS programs in identifying gaps and actions to be undertaken for improved long-term care and treatment of people living with HIV in Sub-Saharan Africa. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019122424.

12.
Pan Afr Med J ; 37: 374, 2020.
Artículo en Francés | MEDLINE | ID: mdl-33796187

RESUMEN

Introduction: since the launch of the "Treatment for All in Cameroon" strategy in 2015, an acceleration plan for antiretroviral (ARV) therapy in Cameroon was implemented, with remarkable progresses. These efforts were accompanied by the risk of developing HIV drug resistance. Then, the World Health Organization (WHO) proposed surveillance of early warning indicators (IAP) for HIV drug resistance. The purpose of this study was to assess the national HIV Drug Resistance Early Warning Indicators (EWI) in Cameroon. Methods: we conducted a retrospective study in the ten regions of Cameroon in December 2017 to evaluate the six EWIs recommended by the WHO in 68 randomly selected HIV care sites. The reporting period ranged from July 2016 to June 2017. Results: national scores were: drug withdrawal within the estimated time frame (EWI1): 66%; retention on antiretroviral therapy 12 months after treatment initiation (EWI2): 66%; stock-out of antiretroviral drugs over a 12-month period (EWI3): 53%; viral load testing coverage (CV) (EWI4): 10%; coverage suppression after 12 months of antiretroviral therapy (EWI5): 73% and practices for ARV drug delivery (EWI6): (100%). Regional scores were similar. Conclusion: the evaluation of EWI in Cameroon is limited and requires urgent interventions, primarily viral load testing coverage, optimal ARVs management and patient´s adherence.

13.
Pan Afr Med J ; 34: 39, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31762906

RESUMEN

Introduction: The number of HIV exposed uninfected (HEU) infants is increasing as vertical transmission is reducing. This subpopulation requires more investigations. This study aimed at comparing the expression level of soluble Fas receptors (FasR) and ligands (FasL) between HIV infected, HEU and unexposed children. Methods: Eighty eight HIV-1infected, 86 HEU and 38 HIV unexposed children were recruited. Soluble FasR and FasL were measured in their plasma. Mann-Whitney U-Test was used to compare groups with 95% confidence. Spearman coefficient was used to test the correlation with CD4 and viral load (VL). Results: Overall plasma levels of FasR were higher than that of FasL. The concentration of FasR and FasL were significantly higher in HIV-1 infected children in comparison to HEU and unexposed children. There was no difference in the plasma level of FasL in HIV infected compared to HEU children. A significant difference was observed between HIV infected children and HEU children (P=0.001) for the FasL. FasR were higher in both HIV infected and unexposed children compared to HEU children. There was a positive correlation (rs=+0.4; p=0.01) in ARV treated children between CD4 count and FasL concentration. Significant negative correlation (rs=-0.3; p=0.040) in ARV naïve children was observed between CD4 percentage and FasL. Significant and positive correlation (rs=+0.4; p=0.008) was observed between the VL and FasL in HIV infected, treated or not. Conclusion: HEU children differ from HIV infected and unexposed children as the level of FasL/R expression is concerned. HEU should be considered different from HIV unexposed although exempt from virus as some immune dysfunctions have been reported among them.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Proteína Ligando Fas/sangre , Infecciones por VIH/epidemiología , Receptor fas/sangre , Adolescente , Recuento de Linfocito CD4 , Camerún , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Masculino , Carga Viral
14.
AIDS Res Ther ; 16(1): 36, 2019 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-31744517

RESUMEN

BACKGROUND: After the launching of the « Test & Treat ¼ strategy and the wider accessibility to viral load (VL), evaluating virological success (VS) would help in meeting the UNAIDS targets by 2020 in Cameroon. SETTING AND METHODS: Cross-sectional study conducted in the Chantal BIYA International Reference Centre for research on HIV/AIDS prevention and management (CIRCB), Yaoundé, Cameroon; data generated between October 2016 and August 2017 amongst adults, adolescents and children at 12, 24, 36 and ≥ 48 months on ART. VS was defined as < 1000 copies/mL of blood plasma and controlled viremia as VL < 50 copies/mL. Data were analysed by SPSS; p < 0.05 considered as significant. RESULTS: 1946 patients (70% female) were enrolled (1800 adults, 105 adolescents, 41 children); 1841 were on NNRTI-based and 105 on PI-based therapy; with 346 patients at M12, 270 at M24, 205 at M36 and 1125 at ≥ M48. The median (IQR) duration on was 48 months (24-48). Overall, VS was 79.4% (95% CI 77.6-81.2) and 67.1% (95% CI 64.9-69.1) had controlled viral replication. On NNRTI-based, VS was 79.9% vs. 71.4% on PIs-based, p = 0.003. By ART duration, VS was 84.1% (M12), 85.9% (M24), 75.1% (M36) and 77.2% (≥ M48), p = 0.001. By age, VS was 75.6% (children), 53.3% (adolescents) and 81.1% (adults), p < 0.001. CONCLUSIONS: In this sub-population of patients receiving ART in Cameroon, about 80% might be experiencing VS, with declining performance at adolescence, with NNRTI-based regimens, and as from 36 months on ART. Thus, improving VS may require an adapted adherence support mechanism, especially for adolescents with long-term treatment in resource-limited settings.


Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Respuesta Virológica Sostenida , Carga Viral/efectos de los fármacos , Adolescente , Adulto , Recuento de Linfocito CD4 , Camerún/epidemiología , Niño , Estudios Transversales , Farmacorresistencia Viral , Femenino , Infecciones por VIH/epidemiología , VIH-1/efectos de los fármacos , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Estudios Retrospectivos
15.
BMC Res Notes ; 12(1): 632, 2019 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-31554515

RESUMEN

OBJECTIVE: Thrombocytopenia is an abnormal decrease in blood platelets, which can affect the prognosis of people living with HIV (PLHIV). In order to assess the burden of this haematological disorder, we evaluated the frequency of thrombocytopenia according to antiretroviral drug combinations, viremia and the immune status of PLHIV. RESULTS: A cross-sectional and analytical study was conducted from June to November 2016 among 310 PLHIV at the "Chantal BIYA" International Reference Centre, Yaoundé, Cameroon. Overall rate of thrombocytopenia was 19.0% (59/310). The rate of thrombocytopenia was 64.6% (42/65) versus 6.9% (17/245) in ART-naïve versus ART-treated patients respectively, p < 0.0001. Following viral load, rate of thrombocytopenia was 15.8% (20/130) in those with undetectable viral load, and 34.1% (27/79) with viral loads > 3 log10 RNA/ml (p = 0.03). As concerns CD4-count, rate of thrombocytopenia was 16.2% (42/259) in those with ≥ 200 CD4/mm3 versus 33.3% (17/51) with < 200 CD4/mm3 (p = 0.0003). After adjusting for sex, ART, viral load and CD4, Viral load and ART exposure were significantly associated with decreased risk of thrombocytopenia (p < 0.05). Thrombocytopenia occurs especially among ART-naïve, high viremia and severe immune-compromised patients. Interestingly, ART coverage appears as an independent factor in preventing the occurrence of thrombocytopenia.


Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Trombocitopenia/diagnóstico , Adolescente , Adulto , Recuento de Linfocito CD4 , Camerún , Niño , Preescolar , Ciudades , Estudios Transversales , Combinación de Medicamentos , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Trombocitopenia/sangre , Trombocitopenia/complicaciones , Viremia/tratamiento farmacológico , Viremia/virología , Adulto Joven
16.
J Antimicrob Chemother ; 74(10): 3011-3015, 2019 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-31299067

RESUMEN

BACKGROUND: In sub-Saharan Africa, detecting resistance-associated mutations (RAMs) at failure of first-line ART with two NRTIs plus an NNRTI predicts improved virological responses to second-line therapy with two NRTIs plus a ritonavir-boosted PI (PI/r). This indicates residual NRTI activity in the presence of RAMs, although additional factors may contribute to the effect. OBJECTIVES: The aim of this study was to investigate the influence of pre-existing RAMs on the outcomes of maintenance monotherapy with ritonavir-boosted darunavir within a randomized trial in Cameroon. METHODS: RAMs were detected in HIV-1 DNA using PBMCs collected at initiation of darunavir/ritonavir monotherapy. Adherence was assessed by pill count and visual analogue scale (VAS). Predictors of virological failure (confirmed or last available viral load >400 copies/mL) were explored by logistic regression analysis. Trial name = MANET (NCT02155101). RESULTS: After NNRTI-based therapy, participants (n = 81) had received PI/r-based therapy for a median of 3.2 years and had a confirmed viral load <60 copies/mL and a median CD4 count of 466 cells/mm3. NRTI and NNRTI RAMs were detected in 39/60 (65.0%) and 41/60 (68.3%) HIV-1 DNA sequences, respectively. Over 48 weeks of monotherapy, 16/81 (19.8%) patients experienced virological failure. After adjusting for age, HIV-1 DNA load, adherence by VAS and RAM status, virological failure was less likely with higher VAS-measured adherence (adjusted OR 0.04, 95% CI 0.01-0.37; P = 0.004) and detectable HIV-1 DNA RAMs (adjusted OR 0.15, 95% CI 0.03-0.82; P = 0.028). CONCLUSIONS: Pre-existing NRTI and NNRTI RAMs are associated with improved virological responses to NRTI-sparing ART in sub-Saharan Africa, indicating a predictive effect that is independent of residual NRTI activity.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , ADN Viral/genética , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/genética , Mutación/genética , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Camerún , Darunavir/uso terapéutico , Farmacorresistencia Viral/efectos de los fármacos , Quimioterapia Combinada/métodos , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de la Transcriptasa Inversa/farmacología , Ritonavir/uso terapéutico , Carga Viral/efectos de los fármacos , Carga Viral/genética
17.
BMC Pediatr ; 19(1): 226, 2019 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-31277610

RESUMEN

BACKGROUND: Sub-Saharan Africa (SSA) alone has nine out of every 10 children living with HIV globally and monitoring in this setting remains suboptimal, even as these children grow older. With scalability of antiretroviral therapy (ART), several HIV-infected children are growing towards adolescence (over 2.1 million), with the potentials to reach adulthood. However, despite an overall reduction in HIV-related mortality, there are increasing deaths among adolescents living with HIV (ADLHIV), with limited evidence for improved policy-making. Of note, strategies for adolescent transition from pediatrics to adult-healthcare are critical to ensure successful treatment response and longer life expectancy. Interestingly, with uptakes in prevention of mother-to-child transmission, challenges in ART programs, and high viremia among children in SSA, the success rate of paediatric ART might be quickly jeopardised, with possible HIV-1 drug-resistance (HIVDR) emergence, especially after years of paediatric ART exposure. Therefore, monitoring ART response in adolescents and evaluating HIVDR patterns might limit disease progression and guide on subsequent ART options for SSA ADLHIV. OBJECTIVES: Among Cameroonian ADLHIV receiving ART, we shall evaluate the rate of immunovirologic failure, acquired HIVDR-associated mutations, HIV-1 subtype distribution, genetic variability in circulating (plasma) versus archived (cellular) viral strains, and HIVDR early warning indicators (EWIs) at different time-points. METHODS: A prospective and observational study will be conducted among 250 ADLHIV (10-19 years old) receiving ART in the centre region of Cameroon, and followed-up at 6 and 12 months after enrollment. Following consecutive sampling at enrolment, plasma viral load and CD4/CD8 count will be measured, and genotypic resistance testing (GRT) will be performed both in plasma and in buffy coat for participants experiencing virological failure (two consecutive viremia > = 1000 copies/ml). Plasma viral load and CD4/CD8 will be monitored for all participants at 6 and 12 months after enrolment. HIVDR-EWIs will be monitored and survival analysis performed during the 12 months follow-up. Primary outcomes are rates of virological failure, acquired-HIVDR, and mortality. DISCUSSION: Our findings will provide evidence-based recommendations to ensure successful transition from paediatrics to adult ART regimens and highlight further needs of active ART combinations, for reduced morbidity and mortality in populations of ADLHIV within SSA.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Estudios Multicéntricos como Asunto/métodos , Estudios Observacionales como Asunto/métodos , Adolescente , Relación CD4-CD8 , Camerún/epidemiología , Niño , Farmacorresistencia Viral , Femenino , Estudios de Seguimiento , Infecciones por VIH/epidemiología , Humanos , Masculino , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Carga Viral , Adulto Joven
18.
PLoS One ; 14(4): e0208963, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30978189

RESUMEN

BACKGROUND: Human Immunodeficiency Virus infection (HIV) remains a public health concern in Cameroon that requires regular surveillance for informed policy-making to guide programmatic interventions. Using data from the 2016 HIV national sentinel survey in Cameroon, we ascertained HIV prevalence and factors associated with risk of infection among pregnant women. METHODS: A cross-sectional study was conducted throughout 2016 in the 10 regions of Cameroon, targeting 7000 first antenatal care (ANC-1) attendees (4000 from urban and 3000 from rural areas) in 60 sentinel health facilities. HIV serological test was performed using the national serial algorithm at the National Reference Laboratory (NRL). Prevalence was determined, and multivariate logistic regression was used to assess determinants of HIV infection, with p-value<0.05 considered statistically significant. RESULTS: Of the 7000 targeted participants, a total of 6859 first ANC-1 attendees were enrolled (98.0% sampling coverage). Median age was 26 [IQR: 21-30] years and 47,40% had a secondary school level of education. The national prevalence of HIV was 5.70% (95% CI: 4.93-6.40) and range from 9.7% in East region to 2.6% in North region. The prevalence was 5.58% (95% CI: 95%: 4.88-6.35) in urban and 5.87% (95% CI: 5.04-6.78) in rural settings. Factors that were associated with HIV infection included marital status, women who were married or living with their partner are less likely to be infected than singles women (aOR = 0.60; 95% CI: 0.46-0.78), multiparity [aOR = 1.5(95%CI:1.0-2.2)] and been living in the Centre, East, North-west and South-west regions. HIV infection was also significantly associated with age, with the risk of being infected increasing with age. CONCLUSION: Pregnant women in Cameroon are still disproportionately infected with HIV compared with the general population (prevalence 4.3%). Preventive actions to curb the epidemic amongst pregnant women should prioritize interventions targeting single pregnant women, who are older, and residing particularly in the Centre, East, North West and South West regions of the country.


Asunto(s)
Infecciones por VIH/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Sífilis/epidemiología , Adulto , Factores de Edad , Camerún/epidemiología , Estudios Transversales , Femenino , Humanos , Estado Civil , Embarazo , Prevalencia , Factores de Riesgo , Población Rural , Vigilancia de Guardia , Adulto Joven
19.
PLoS One ; 14(3): e0213900, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30883591

RESUMEN

BACKGROUND: There are limited data on protease inhibitor (PI)-based antiretroviral therapy (ART) amongst children in resource-limited settings, for informing on optimal paediatric regimens. OBJECTIVE: To evaluate therapeutic response to PI-based ART amongst HIV-infected Cameroonian children. METHODS: A retrospective study was conducted amongst children aged 2-18 years receiving a PI-based ART at the Essos Hospital Centre (EHC), Yaounde, Cameroon. Primary end points were therapeutic success on PI-based ART, defined as clinical success (WHO I/II clinical stage), immunological success (CD4 ≥ 500/mm3) and viral suppression (viral load [VL]<1000 copies/ml). Factors associated with therapeutic success were assessed in uni- and multivariate analysis using SPSS software v.2.0; with p<0.05 considered statistically significant. RESULTS: A total of 71 eligible children on PI-based ART were enrolled (42 on initial and 29 on substituted regimens), with a median age of 8 [IQR: 5-12] years and mean duration on ART of 7 years. Following therapeutic responses, all (100%) experienced clinical success, 95.2% experienced immunological success (91.7% on initial and 97.2% on substituted PI/r-based regimens) and 74.7% viral suppression. In univariate analysis, viral suppression was associated with: younger age (p<0.0001), living with parents as opposed to guardians (p = 0.049), and the educational level (p<0.0001). In multivariate analysis, only the age ranges of 10-14 years (OR: 0.22 [0.07-0.73]) and 15-18 years (OR: 0.08 [0.02-0.57]), were determinants of poor viral suppression. CONCLUSION: Among these Cameroonian children, PI-based ART confers favourable clinical and immunological outcomes. The poor rate of viral suppression was mainly attributed to adolescence (10-18 years).


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Adolescente , Recuento de Linfocito CD4 , Camerún , Niño , Preescolar , Estudios de Cohortes , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Análisis Multivariante , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Insuficiencia del Tratamiento , Carga Viral/efectos de los fármacos
20.
BMC Infect Dis ; 19(1): 246, 2019 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-30871487

RESUMEN

BACKGROUND: With the phase-out of stavudine (d4T), change to first-line regimens with zidovudine (AZT) or tenofovir (TDF) in resource-limited settings (RLS) might increase risks of cross-resistance to nucleos(t) ide reverse transcriptase inhibitors (NRTI). This would restrict the scope of switching to the World Health Organisation (WHO)-recommended standard second-line combinations (SLC) without HIV drug resistance (HIVDR)-testing in routine clinical practice. METHODS: An observational study was conducted among 101 Cameroonian patients (55.4% male, median [IQR] age 34 [10-41] years) failing first-line antiretroviral therapy (ART) in 2016, and stratified into three groups according to NRTIs exposure: exposure to both thymidine analogues AZT "and" D4T (group-A, n = 55); exposure to both TDF and AZT "or" D4T (group-B, n = 22); exposure solely to D4T (group-C, n = 24). Protease-reverse transcriptase HIVDR was interpreted using the HIVdb penalty scores (≥60: high-resistance; 20-59: intermediate-resistance; < 20: susceptible). The acceptable threshold for potential-efficacy was set at 80%. RESULTS: The median [IQR] CD4, viral RNA, and time on ART, were respectively 129 [29-466] cells/µl, 71,630 [19,041-368,000] copies/ml, and 4 [2-5] years. Overall HIVDR-level was 89.11% (90/101), with 83.2% harbouring M184 V (high-level 3TC/FTC-resistance) and only 1.98% (2/101) major HIVDR-mutations to ritonavir-boosted protease-inhibitors (PI/r). Thymidine-analogue mutations (TAMs)-1 [T215FY (46.53%), M41 L (22.77%), L210 W (8.91%)], with cross-resistance to AZT and TDF, were higher compared to TAMs-2 [D67N (21.78%), K70R (19.80%), K219QE (18.81%)]. As expected, K65R was related with TDF-exposure: 0% (0/55) in group-A, 22.72% (5/22) group-B, 4.17% (1/24) group-C (p = 0.0013). The potential-efficacy of AZT vs. TDF was respectively 43.64% (24/55) vs. 70.91% (39/55) in group-A (p = 0.0038); 63.64% (14/22) vs. 68.28% (15/22) in group-B (p = 1.0000); and 37.50% (9/24) vs. 83.33% (20/24) in group-C (p = 0.0032). CRF02_AG was the prevailing subtype (63.40%), followed by CRF11.cpx (8.91%), A1 (7.92%), G (5.94%); without any significant effect of the subtype-distribution on HIVDR (92.2% in CRF02_AG vs. 83.8% in non-AG; p = 0.204). CONCLUSION: First-line ART-failure exhibits high-level NRTI-resistance, with potential lower-efficacy of AZT compared to TDF. Significantly, using our 80% efficacy-threshold, only patients without NRTI-substitution on first-line could effectively switch to SLC following the WHO-approach. Patients with multiple NRTI-substitutions (exposed to both thymidine-analogues and TDF) on first-line ART would require HIVDR-testing to select active NRTIs for SLC.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Adolescente , Adulto , Camerún , Niño , Farmacorresistencia Viral , Femenino , Infecciones por VIH/virología , Transcriptasa Inversa del VIH , VIH-1/genética , VIH-1/fisiología , Humanos , Masculino , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Ritonavir/administración & dosificación , Estavudina/administración & dosificación , Tenofovir/administración & dosificación , Adulto Joven , Zidovudina/administración & dosificación
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