Viral suppression in the era of transition to dolutegravir-based therapy in Cameroon: Children at high risk of virological failure due to the lowly transition in pediatrics.

This study aimed to compare viral suppression (VS) between children, adolescents, and adults in the frame of transition to dolutegravir (DTG)-based antiretroviral therapy (ART) in the Cameroonian context. A comparative cross-sectional study was conducted from January 2021 through May 2022 amongst ART-experienced patients received at the Chantal BIYA International Reference Centre in Yaounde-Cameroon, for viral load (VL) monitoring. VS was defined as VL < 1000 copies/mL and viral undetectability as VL < 50 copies/mL. Chi-square and multivariate binary logistic regression models were used to identify factors associated with VS. Data were analyzed using SPSS v.20.0 (SPSS Inc., Chicago, Illinois), with P < .05 considered significant. A total of 9034 patients (72.2% females) were enrolled. In all, there were 8585 (95.0%) adults, 227 (2.5%) adolescents, and 222 (2.5%) children; 1627 (18.0%) were on non-nucleoside reverse transcriptase-based, 290 (3.2%) on PI-based, and 7117 (78.8%) on DTG-based ART. Of those on DTG-based ART, only 82 (1.2%) were children, 138 (1.9%) adolescents, and 6897 (96.9%) adults. Median (interquartile range) duration on ART was 24 (12-72) months (24 months on Tenofovir + Lamivudine + Dolutegravir [TLD], 36 months on other first lines, and 84 months on protease inhibitors boosted with ritonavir-based regimens). Overall, VS was 89.8% (95% confidence interval: 89.2-90.5) and viral undetectability was 75.7% (95% confidence interval: 74.8-76.7). Based on ART regimen, VS on Non-nucleoside reverse transcriptase-based, protease inhibitors boosted with ritonavir-based, and DTG-based therapy was respectively 86.4%, 59.7%, and 91.8%, P < .0001. Based on ART duration, VS was respectively 51.7% (≤24 months) versus 48.3% (≥25 months), P < .0001. By gender, VS was 90.9% (5929) in females versus 87.0% (2183) in males, P < .0001; by age-range, VS moved from 64.8% (144) in children, 74.4% (169) adolescents, to 90.8% (7799) adults, P < .0001. Following multivariate analysis, VS was associated with adulthood, female gender, TLD regimens, and combination antiretroviral therapy duration > 24 months (P < .05). In Cameroon, ART response indicates encouraging rates of VS (about 9/10) and viral undetectability (about 3/4), driven essentially by access to TLD based regimens. However, ART response was very poor in children, underscoring the need for scaling-up pediatric DTG-based regimens.

The mother-to-child transmission of HIV-1 and profile of viral reservoirs in pediatric population: A systematic review with meta-analysis of the Cameroonian studies.

BACKGROUND: The mother-to-child transmission of HIV-1 (MTCT) remains on the major route of HIV-transmission among pediatric populations in Africa. Though a prevention of MTCT (PMTCT) high-priority country, data on the MTCT burdens in Cameroon remains fragmented. OBJECTIVE: We sought to assess the pooled MTCT rate, its risk-factors, and to characterize viral reservoirs of infected-children in Cameroon. METHODS: All relevant observational cohort and cross-sectional studies conducted in Cameroon were searched from PubMed, African Journals Online, Google scholar, ScienceDirect and academic medical education databases. Heterogeneity and publication bias were respectively assessed by the I2 statistic and the Egger/funnel plot test. Meta-analysis was performed using the random effects model. MTCT rate >5% was considered as "high". This review was registered in the Prospero database, CRD42021224497. RESULTS: We included a total of 29 studies and analyzed 46 684 children born from HIV-positive mothers. The overall rate of MTCT was 7.00% (95% CI = 6.07-8.51). According to regions, the highest burden was in Adamaoua-region (17.51% [95% CI:14.21-21.07]) with only one study found. PMTCT option-B+ resulted in about 25% reduction of MTCT (8.97% [95% CI: 8.71-9.24] without option-B+ versus 2.88% [95% CI: 5.03-9.34] with option-B+). Regarding risk-factors, MTCT was significantly associated with the absence of PMTCT-interventions both in children (OR:5.40 [95% CI: 2.58-11.27]) and mothers (OR: 3.59 [95% CI: 2.15-5.99]). Regarding viral reservoirs, a pro-viral DNA mean of 3.34±1.05 log10/mL was observed among 5/57 children and archived HIV drug resistance mutations were identified in pro-viral DNA marker among 21/79 infected-children. CONCLUSION: In spite of the dropdown in MTCT following option-B+ implementation, MTCT remains high in Cameroon, with substantial disparities across regions. Thus, in this era of option-B+, achieving MTCT elimination requires interventions in northern-Cameroon. The variation in pro-viral load in infected-children underlines the relevance of characterizing viral reservoirs for possible infection control in tropical settings.

HIV Pre-exposure Prophylaxis Uptake and Continuation Among Key Populations in Cameroon: Lessons Learned From the CHAMP Program.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is proven to be a highly effective HIV prevention method for key populations. However, its scale-up in resource-limited settings remains suboptimal. This paper seeks to describe PrEP initiation and continuation among key populations in Cameroon. METHODOLOGY: From June 2019 through October 2020, we collected routine program data on PrEP uptake and continuation among female sex workers (FSWs) and men who have sex with men (MSM) in the Continuum of prevention, care and treatment of HIV/AIDS with Most-at-risk Populations (CHAMP) program in Cameroon. PrEP was offered to clients who tested negative for HIV and were assessed to potentially benefit from PrEP. Using survival analysis, we identified factors associated with PrEP discontinuation over time with significance set at 5%. RESULTS: Overall, 27,750 clients were sensitized for PrEP of whom 3,138 persons were eligible to start PrEP and 1,409 (45%; FSW: 691 and MSM: 718) initiated PrEP. The PrEP continuation rate was 37% at 3 months, 28% at 6 months and 19% at 12 months. PrEP discontinuation was significantly higher among FSW than MSM [adjusted hazard ratio (aHR) 1.5 (95% CI: 1.2 to 1.9)] in Yaounde [aHR 1.5 (95% CI: 1.2 to 1.9)] and Bafoussam/Bertoua [aHR 3.1 (2.2-4.5)] relative to Douala. Discontinuation was lower among those with moderate [aHR 0.3 (0.3-0.4)] or good adherence [aHR 0.4 (0.3-0.6)] compared with poor adherence (all P < 0.001). CONCLUSION: Differentiated approaches to deliver PrEP, create demand, and provide more intensive support for adherence and continuation may support scale-up of PrEP in Cameroon for equitable and prolonged impact on HIV prevention.

First case of Dolutegravir and Darunavir/r multi drug-resistant HIV-1 in Cameroon following exposure to Raltegravir: lessons and implications in the era of transition to Dolutegravir-based regimens.

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.

Maternal age, infant age, feeding options, single/multiple pregnancy, type of twin sets and mother-to-child transmission of HIV.

BACKGROUND: Some risk factors for mother-to-child transmission (MTCT) of HIV have been identified. To further reduce MTCT, other risk factors were evaluated. MATERIALS AND METHODS: A retrospective study on early infant diagnosis was conducted. Two-sided chi-square test was used to assess associations with infant HIV status. RESULTS: A total of 15 233 HIV-infected mothers and 15 404 infants were recruited. MTCT rate was 9.34%. Only 3.8% of infants born to mothers on antiretroviral treatment were infected. Under nevirapine, 4.1% of infants were infected. MTCT increased with infant' age at testing. Younger mothers tend to transmit more HIV (P = 0.003). More children were infected in single pregnancies compared with multiple pregnancies, P < 0.001. There were more infections in male-female twins' sets (P = 0.037). CONCLUSIONS: Maternal age, type of pregnancy and twins' sets are new MTCT risk factors. Strategies to further decrease transmission through family planning, pre/post natal consultations and clinical practices are needed.

Next-generation sequencing provides an added value in determining drug resistance and viral tropism in Cameroonian HIV-1 vertically infected children.

With limited and low-genetic barrier drugs used for the prevention of mother-to-child transmission (PMTCT) of HIV in sub-Saharan Africa, vertically transmitted HIV-1 drug-resistance (HIVDR) is concerning and might prompt optimal pediatric strategies.The aim of this study was to ascertain HIVDR and viral-tropism in majority and minority populations among Cameroonian vertically infected children.A comparative analysis among 18 HIV-infected children (7 from PMTCT-exposed mothers and 11 from mothers without PMTCT-exposure) was performed. HIVDR and HIV-1 co-receptor usage was evaluated by analyzing sequences obtained by both Sanger sequencing and ultra-deep 454-pyrosequencing (UDPS), set at 1% threshold.Overall, median (interquartile range) age, viremia, and CD4 count were 6 (4-10) years, 5.5 (4.9-6.0) log10 copies/mL, and 526 (282-645) cells/mm, respectively. All children had wild-type viruses through both Sanger sequencing and UDPS, except for 1 PMTCT-exposed infant harboring minority K103N (8.31%), born to a mother exposed to AZT+3TC+NVP. X4-tropic viruses were found in 5 of 15 (33.3%) children (including 2 cases detected only by UDPS). Rate of X4-tropic viruses was 0% (0/6) below 5 years (also as minority species), and became relatively high above 5 years (55.6% [5/9], P = .040. X4-tropic viruses were higher with CD4 ≤15% (4/9 [44.4%]) versus CD4 >15% (1/6 [16.7%], P = .580); similarly for CD4 ≤200 (3/4 [75%]) versus CD4 >200 (2/11 [18.2%] cells/mm, P = .077.NGS has the ability of excluding NRTI- and NNRTI-mutations as minority species in all but 1 children, thus supporting the safe use of these drug-classes in those without such mutations, henceforth sparing ritonavir-boosted protease inhibitors or integrase inhibitors for the few remaining cases. In children under five years, X4-tropic variants would be rare, suggesting vertical-transmission with CCR5-tropic viruses and possible maraviroc usage at younger ages.

Feasibility Study of HIV Sentinel Surveillance using PMTCT data in Cameroon: from Scientific Success to Programmatic Failure.

BACKGROUND: In low-income countries (LICs), HIV sentinel surveillance surveys (HIV-SSS) are recommended in between two demographic and health surveys, due to low-cost than the latter. Using the classical unlinked anonymous testing (UAT), HIV-SSS among pregnant women raised certain ethical and financial challenges. We therefore aimed at evaluating how to use prevention of mother-to-child transmission of HIV (PMTCT) routine data as an alternative approach for HIV-SSS in LICs. METHODS: A survey conducted through 2012 among first antenatal-care attendees (ANC1) in the ten regions of Cameroon. HIV testing was performed at PMTCT clinics as-per the national serial algorithm (rapid test), and PMTCT site laboratory (PMTCT-SL) performances were evaluated by comparison with results of the national reference laboratory (NRL), determined as the reference standard. RESULTS: Acceptance rate for HIV testing was 99%, for a total of 6521 ANC1 (49 · 3% aged 15-24) enrolled nationwide. Among 6103 eligible ANC1, sensitivity (using NRL testing as the reference standard) was 81 · 2%, ranging from 58 · 8% (South region) to 100% (West region); thus implying that 18 · 8% HIV-infected ANC1 declared HIV-negative at the PMTCT-SL were positive from NRL-results. Specificity was 99 · 3%, without significant disparity across sites. At population-level, this implies that every year in Cameroon, ~2,500 HIV-infected women are wrongly declared seronegative, while ~1,000 are wrongly declared seropositive. Only 44 · 4% (16/36) of evaluated laboratories reached the quality target of 80%. CONCLUSIONS: The study identified weaknesses in routine PMTCT HIV testing. As Cameroon transitions to using routine PMTCT data for HIV-SSS among pregnant women, there is need in optimizing quality system to ensure robust routine HIV testing for programmatic and surveillance purposes.

HIV-1 Early Infant Diagnosis is an Effective Indicator of the Prevention of Mother-to-Child Transmission Program Performance: Experience from Cameroon.

BACKGROUND: Despite improvement in HIV prevention of mother-to-child transmission (PMTCT), there are still over 1,500 African infants newly infected daily. PMTCT elimination requires antiretroviral therapy (ART) throughout pregnancy and breastfeeding periods, while early infant diagnosis (EID) of HIV implies early treatment for those infected. Our study aimed at assessing the utility of EID program data in evaluating the implementation of PMTCT program in Cameroon, and in identifying the efficacy of existing PMTCT interventions and breastfeeding options on the events of HIV vertical transmission. METHODS: A study was conducted from 2010-2011 using PMTCT data from EID sites of six regions of Cameroon. PMTCT ARV regimens, breastfeeding options, and the child's HIV DNA-polymerase chain reaction (PCR) results were recorded. Statistical analyses were performed using Mann Whitney U and Fisher exact tests, with p<0.05 considered significant. RESULTS: A total of 2,505 mother-child pairs received ART, resulting is 4.3% (93) vertical transmission, against 31.3% (284/906) among mother-child pairs without exposure to any PMTCT intervention; p<0.00001. A statistically significant difference (p<0.00001) was also found between formula feeding (FF) (5.9%) versus exclusive breastfeeding (EBF) (12.5%), as well as between EBF versus mixed feeding (MF) (30%). With FF, when both mother-child pairs received PMTCT, only 2.9% (47/1603) vertical transmission was recorded versus 19.9% (48/241) for mother-child pairs without intervention; p<0.00001. Transmission rates were similar across infant age range [2.7% (10/376) for age ≤6 weeks, versus 2.5% (43/1807) for age >6 weeks-6 months]. Interestingly, babies aged 6 weeks receiving FF showed a significantly lower transmission rate (3.2%, 9/277) as compared to their counterparts with EBF (7.7%, 12/156); p<0.00001. CONCLUSION: Using EID dataset, it appears that considerable reduction in HIV MTCT may be achievable through access to ARV (option B+) and adequate infant feeding option (especially FF) in Cameroon. EID programme is therefore an effective routine approach for PMTCT programme evaluation in resource-limited settings.

Evaluation of the nutritional status of infants from mothers tested positive to HIV/AIDS in the health district of Dschang, Cameroon.

INTRODUCTION: Poor infant feeding practices are common in Africa, resulting in physical and intellectual developmental impairments. Good feeding practices are crucial, especially in the first year of growth. HIV/AIDS has worsened the clinical and nutritional status of both mothers and their children, exacerbating high rates of malnutrition. The aim of this study was to assess by participative approach, the nutritional status of infants from mothers tested positive to HIV in the health district of Dschang. METHODS: This is a cross sectional study with a period of recruitment of 2 years (2010-2012). Data Collection was done by the aim of a personal slip followed by training to strengthen the nutritional and hygienic capacity of targeted parents. Height and weight of infants were measured and body mass index (BMI) calculated. RESULTS: Significant difference (p ≤ 0.05) was noticed in height-for-age z-score (HAZ) of girls aged between 1 to 2 years compared to 1-year old girls as well as to boys of all ages, defining them as stunted. Furthermore, the weight-for-age z-score (WAZ) results indicate that both girls and boys of all age are in moderate state of malnutrition. The results of BMI thinness classified according to gender and age groups, indicates that most infants (68/130, 52.3%) showed grade 2 thinness predominantly in 2-years old both boys and girls. However, no participants fall within the normal category for age and sex, as well as overweight and obesity categories. CONCLUSION: Undernutrition exists among infants from mothers tested positive to HIV residing in Dschang, as most of the infants are underweight, and malnourished.

Evaluation of OraQuick® HIV-1/2 as Oral Rapid Test.

As Cameroon scales up its national HIV/AIDS control program, evaluating the performance of commercially available tests for accurate and cost effective diagnostics becomes essential. A cross-sectional study assessed the performance of an HIV oral rapid test. A total of 1520 participants consented to participate in the study. After counselling, they were tested for HIV using the national algorithm followed by OraQuick. Results of the national algorithm were compared to those of OraQuick, for sensitivity, specificity, positive predictive and negative predictive values. 62% of participants were male, and 1% was reported HIV-positive following the national algorithm. The OraQuick test had 93% sensitivity, 99% specificity, 99.93% NPV and 90% PPV (95% CI, Kappa 0.965). Though more expensive (2-6x) compared to the national algorithm tests, oral mucosal transudate-based test demonstrated good performance. Therefore, it could be implemented in resource-constrained settings if subsidized and could increase participation since less invasive with no blood accident exposure.