Changes in access to viral load testing, incidence rates of viral load suppression and rebound following the introduction of the 'universal test and treat' guidelines in Cameroon: A retrospective follow-up analysis.

Cameroon adopted and started implementing in 2016, the 'universal test and treat' (UTT) guidelines to fast-track progress towards the 95-95-95 ambitious targets to end the HIV epidemic. Achieving the third 95 (viral load suppression) is the most desirable target in HIV care. We aimed to evaluate the effectiveness of this novel approach on access to viral load testing (VLT), viral suppression (VLS), and viral load rebound (VLR). A retrospective cohort study was conducted at The Nkongsamba Regional Hospital to compare VLT outcomes between the pre-UTT (2002 to 2015) and the post-UTT (2016 to 2020) periods. We used a data extraction form to collect routine data on adult patients living with HIV. We measured uptake levels of the first and serial VLT and compared the incidence rates of VLS (VL<1000 copies/ml) and viral load rebound (VLR) before and after introducing the UTT approach using Kaplan Meier plots and log-rank tests. Cox regression was used to screen for factors independently associated with VLS and VLR events between the guideline periods. Access to initial VLT increased significantly from 6.11% to 25.56% at 6 months and from 12.00% to 73.75% at 12 months before and after introducing the UTT guidelines respectively. After a total observation time at risk of 17001.63 person-months, the UTT group achieved an incidence rate of 90.36 VLS per 1000 person-months, four-fold higher than the 21.71 VLS per 1000 person-months observed in the pre-UTT group (p<0.0001). After adjusting for confounding, the VLS rate was about 6-fold higher in the UTT group than in the pre-UTT group (adjusted Hazard Rate (aHR) = 5.81 (95% confidence interval (95%CI): 4.43-7.60). The incidence of VLR increased from 12.60 (95%CI: 9.50-16.72) to 19.11 (95%CI: 14.22-25.67) per 1000 person-months before and after the introduction of UTT guidelines respectively. After adjusting, VLR was more than twice as high in the UTT group than in the pre-UTT group (aHR = 2.32, 95%CI: 1.30-4.13). Increased access to initial VLT and higher rates of VLS have been observed but there are concerns that the suppressed viral load may not be durable since the introduction of the UTT policy in this setting.

The declining trend in HIV prevalence from population-based surveys in Cameroon between 2004 and 2018: myth or reality in the universal test and treat era?

BACKGROUND: HIV remains an epidemic of major public health importance in Cameroon but a decline in HIV prevalence has been observed according to population-based surveys conducted in 2004, 2011 and 2018. We sought to review current evidence for declining HIV prevalence despite increasing survival owing to 'universal test and treat' and to explore the reason for the decrease, particularly the role of behavioural change. METHODS: We conducted a secondary analysis using HIV prevalence, behavioural and social determinants data of the Demographic and Health Survey Program databases. Trend lines were fitted to data that were available for a minimum of three points in time during the 1991-2018 period. Regression coefficients associated p-values and 95% confidence intervals were obtained using Microsoft Excel software. RESULTS: Overall adult HIV prevalence decreased significantly from 5.4% (95%CI: 4.8-6.0) in 2004 to 4.3% (95%CI: 3.8-4.8) in 2011 and further down to 2.7% (95%CI: 2.3-3.1) in 2018 at a rate of about 1.4% every septennium (ß = -1.4, R² = 0.98, p = 0.03). Yet, the number of persons surviving with HIV increased from about 0.05 million in 1991 to 0.5 million in 2018 corresponding to an increase in access to antiretroviral therapy from less than 10% to universal coverage of 80% respectively. Concurrent reductions in risky sexual behaviours were observed: a delayed sexual debut by one year, decreased sexual violence by 7%, decreased polygamous unions by 16%, decreased multiple sexual partners by 15.3% and increased condom use by 26.3%. CONCLUSION: The observed decline in HIV prevalence is statistically valid and reflects the observed decline in risky sexual behaviour that need to be sustained by the National HIV programme. Though universal access to ART has increased the number of persons surviving with HIV, this has not led to an increased prevalence of HIV in a setting with a rising population.

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

BACKGROUND: While dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroon and Senegal. METHODS: We used data collected over 2010-2015 in the 2LADY trial/post-trial cohort. Patients with first-line antiretroviral therapy (ART) failure were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (TDF/FTC LPV/r; arm A), abacavir + didanosine + lopinavir/ritonavir (arm B), or tenofovir/emtricitabine + darunavir/ritonavir (arm C). Costs (US dollars, 2016), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were computed for each country over 24 months of follow-up and extrapolated to 5 years using a simulated patient-level Markov model. We assessed uncertainty using cost-effectiveness acceptability curves, scenarios and prices threshold analysis. RESULTS: In each country, over 24 months, arm A was significantly less costly than arms B and C (incremental costs ranging from US$410-$US721 and US$468-US$546 for B and C vs A, respectively) and offered similar health benefits (incremental QALY: - 0.138 to 0.023 and - 0.179 to 0.028, respectively). Over 5 years, arm A remained the least costly, health benefits not being significantly different between arms. Compared with arms B and C, in each study country, Arm A had a ≥ 95% probability of being cost-effective for a large range of cost-effectiveness thresholds, irrespective of the scenario considered. CONCLUSIONS: Using TDF/FTC LPV/r as a bPI-based second-line regimen provided the best economic value in the three study countries. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00928187.

Epidemiology and antifungal susceptibility testing of non-albicansCandida species colonizing mucosae of HIV-infected patients in Yaoundé (Cameroon).

Non-albicans Candida (NAC) species have emerged as potent pathogenic yeasts among HIV-infected patients. Authors evaluated the epidemiology and antifungal susceptibility testing of non-albicansCandida species colonizing Yaoundé (capital of the Republic of Cameroon, Central Africa) HIV-infected patients. The mucosal specimens were collected and submitted to the mycological diagnosis. Yeast isolates were identified by the Matrix Assisted Laser Desorption Ionisation - Time of Flight Mass Spectrometry (MALDI-TOF MS). The antifungal susceptibility testing was achieved by the CLSI-M27 protocols, and the interpretation of clinical break points (CBPs) and epidemiological cutoff values were in accordance with the CLSI-M60 and M59 recommendations. Four hundred and two patients were recruited and 1218 samples collected. The colonisation frequency was 24.1% and 304 yeasts isolated. Yeast isolates were 113 (37.2%) C. albicans, 2 (0.7%) C. africana and 172 (56.6%) NAC isolates. The NAC isolates were grouped into 13 species including C. krusei (18.1%), C. glabrata (10.9%), C. tropicalis (8.5%) and C. parapsilosis (5.9%) as the major ones. All the isolates appeared to be wild-type for amphotericin B and itraconazole. One (1/33) isolate of C. glabrata was resistant to fluconazole. C. arapsilosis isolates appeared all susceptible to fluconazole. C. tropicalis isolates presented 50% (13/26) resistance to fluconazole. The achieved results bring out new insights about epidemiology of NAC species in Cameroon. The results also highlight the resistance of NAC species to current antifungal drugs.

Heterogeneity of virological suppression in the national antiretroviral programme of Cameroon (ANRS 12288 EVOLCAM).

OBJECTIVES: In terms of HIV infection, western and central Africa is the second most affected region world-wide, and the gap between the regional figures for the testing and treatment cascade and the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets is particularly worrying. We assessed the prevalence of virological suppression in patients routinely treated in 19 hospitals in Cameroon. METHODS: A cross-sectional survey was performed in adult patients receiving antiretroviral therapy (ART) in the Centre and Littoral regions. The prevalences of virological suppression (<1000 HIV-1 RNA copies/mL) were compared among all 19 hospitals using the χ2 test. Potential individual and health care-related determinants of virological suppression were assessed using multivariate logistic regression models. RESULTS: A total of 1700 patients (74% women; median age 41 years; median time on ART 3.7 years) were included in the study. The prevalence of virological suppression was 82.4% overall (95% confidence interval 80.5-84.2%). It ranged from 57.1 to 97.4% according to the individual hospital (P < 0.001). After adjustment, virological suppression was associated with age, CD4 cell count at ART initiation, disclosure of HIV status to family members, interruption of ART for more than two consecutive days, and location of patient's residence and hospital (rural/urban). These factors did not explain the heterogeneity of virological suppression between the study hospitals (P < 0.001). CONCLUSIONS: The overall prevalence of virological suppression was reassuring. Nevertheless, the heterogeneity of virological suppression among hospitals highlights that, in addition to programme-level data, health facility-level data are crucial in order to tailor the national AIDS programme's interventions with a view to achieving the third UNAIDS 90 target.

Benefits of task-shifting HIV care to nurses in terms of health-related quality of life in patients initiating antiretroviral therapy in rural district hospitals in Cameroon [Stratall Agence Nationale de Recherche sur le SIDA (ANRS) 12110/Ensemble pour une Solidarité Thérapeutique Hospitalière en Réseau (ESTHER) substudy].

OBJECTIVES: The World Health Organization (WHO) recommends task-shifting HIV care to nurses in low-resource settings with limited numbers of physicians. However, the effect of such task-shifting on the health-related quality of life (HRQL) of people living with HIV (PLHIV) has seldom been evaluated. We aimed to investigate the effect of task-shifting HIV care to nurses on HRQL outcomes in PLHIV initiating antiretroviral therapy (ART) in rural district hospitals in Cameroon. METHODS: Outcomes in PLHIV were longitudinally collected in the 2006-2010 Stratall trial. PLHIV were followed up for 24 months by nurses and/or physicians. Six HRQL dimensions were assessed during face-to-face interviews using the WHO Quality of Life (WHOQOL)-HIV BREF scale: physical health; psychological health; independence level; social relationships; environment; and spirituality/religion/personal beliefs. The degree of task-shifting was estimated using a consultant ratio (i.e. the ratio of nurse-led to physician-led visits). The effect of task-shifting and other potential correlates on HRQL dimensions was explored using a Heckman two-stage approach based on linear mixed models to adjust for the potential bias caused by missing data in the outcomes. RESULTS: Of 1424 visits in 440 PLHIV (70.5% female; median age 36 years; median CD4 count 188 cells/µL at enrolment), 423 (29.7%) were task-shifted to nurses. After multiple adjustment, task-shifting was associated with higher HRQL level for four dimensions: physical health [coefficient 0.7; 95% confidence interval (CI) 0.1-1.2; P = 0.01], psychological health (coefficient 0.5; 95% CI 0.0-1.0; P = 0.05), independence level (coefficient 0.6; 95% CI 0.1-1.1; P = 0.01) and environment (coefficient 0.6; 95% CI 0.1-1.0; P = 0.02). CONCLUSIONS: Task-shifting HIV care to nurses benefits the HRQL of PLHIV. Together with the previously demonstrated comparable clinical effectiveness of physician-based and nurse-based models of HIV care, our results support the WHO recommendation for task-shifting.

Cryptoccocal meningitis in Yaoundé (Cameroon) HIV infected patients: Diagnosis, frequency and Cryptococcus neoformans isolates susceptibility study to fluconazole.

Cryptococcal meningitis is a mycosis encountered especially in patients with Acquired Immunodeficiency Syndrome and is fatal in the absence of treatment. Information on epidemiology, diagnosis and susceptibility profile to antifungal drugs, are scarce in Cameroon. Authors evaluated the diagnosis possibilities of the cryptococcal meningitis in Cameroon, and studied the antifungal susceptibility of isolated strains to fluconazole, used as first line treatment of the disease in Cameroon. Between December 2009 and July 2011, 146 cerebrospinal fluids obtained from HIV patients with suspicion of meningitis were analysed. The diagnosis procedure involved macroscopic and cyto-chemical analysis, India ink test, culture on Sabouraud chloramphenicol medium and antigen latex agglutination test. Antifungal susceptibility testing of isolated strains to fluconazole was done by the E-test(®) method. The diagnosis of cryptococcal meningitis gave 28.08% positive cases. Among these patients, 80% were at stages III and IV and 20% at stage I of the HIV infection, according to the WHO previous classification. Cyto-chemical analysis showed current findings in the case of cryptococcal meningitis. India ink test and latex agglutination test exhibited very high sensitivity and specificity (>94%). Fluconazole antifungal susceptibility testing gave MICs lower than 32µg/mL to 92.7% of isolated strains and MICs greater than this value to 7.3% of isolates. These results showed that cryptococcal meningitis remains a real problem among HIV infected patients in Yaoundé. The emergence of fluconazole reduced susceptibility strains is worrying. Nevertheless, efficacy of rapid detection tests is interesting because this will help in rapid diagnosis and treatment of patients.

Patterns of adherence to antiretroviral therapy and HIV drug resistance over time in the Stratall ANRS 12110/ESTHER trial in Cameroon.

OBJECTIVES: The emergence of HIV drug resistance is a crucial issue in Africa, where second-line antiretroviral therapy (ART) is limited, expensive and complex. We assessed the association between adherence patterns and resistance emergence over time, using an adherence measure that distinguishes low adherence from treatment interruptions, in rural Cameroon. METHODS: We performed a cohort study among patients receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART in nine district hospitals, using data from the Stratall trial (2006-2010). Genotypic mutations associated with antiretroviral drug resistance were assessed when 6-monthly HIV viral loads were > 5000 HIV-1 RNA copies/mL. ART adherence data were collected using face-to-face questionnaires. Combined indicators of early (1-3 months) and late (6 months to t - 1; t is the time point when the resistance had been detected) adherence were constructed. Multivariate logistic regression and Cox models were used to assess the association between adherence patterns and early (at 6 months) and late (after 6 months) resistance emergence, respectively. RESULTS: Among 456 participants (71% women; median age 37 years), 45 developed HIV drug resistance (18 early and 27 late). Early low adherence (< 80%) and treatment interruptions (> 2 days) were associated with early resistance [adjusted odds ratio (95% confidence interval) 8.51 (1.30-55.61) and 5.25 (1.45-18.95), respectively]. Early treatment interruptions were also associated with late resistance [adjusted hazard ratio (95% confidence interval) 3.72 (1.27-10.92)]. CONCLUSIONS: The emergence of HIV drug resistance on first-line NNRTI-based regimens was associated with different patterns of adherence over time. Ensuring optimal early adherence through specific interventions, adequate management of drug stocks, and viral load monitoring is a clinical and public health priority in Africa.

Genotyping and antifungal susceptibility testing of Cryptococcus neoformans isolates from Cameroonian HIV-positive adult patients.

Cryptococcus neoformans is the most common cause of meningitis amongst adult Africans with HIV/AIDS. The widespread use of fluconazole may lead to the emergence of isolates with reduced susceptibility. We studied C. neoformans isolates from HIV-infected patients with cryptococcal meningitis. Genotyping and antifungal testing were performed to assess the genetic diversity, occurrence of mixed infections and in vitro activity of antifungal agents. Isolates were recovered from cerebrospinal fluid prior to systemic antifungal treatment. Six isolates were studied for each sample (a total of 114 isolates from 19 patients). Serotyping was performed via LAC 1 and CAP 64 gene amplification and genotyping was performed using phage M13 core, (GACA)4 and (GTG)5 primers and restriction polymorphism analysis of the URA5 gene. Susceptibilities for amphotericin B, flucytosine, fluconazole, voriconazole and posaconazole were tested by the Sensititre YeastOne® method. All strains were identified as C. neoformans var. grubii serotype A. We identified nine major genotypes. Up to two genotypes were identified in the same sample. None of the isolates were resistant to the studied drugs. However, 13 of 114 strains exhibited a reduced susceptibility to fluconazole and 13 of 114 strains exhibited a reduced susceptibility to flucytosine. No correlation was found between the genotype and susceptibility. This study confirms the prevalence of C. neoformans serotype A in Cameroon. Two genotypes may be responsible for a single episode of cryptococcosis. The possibility of mixed infection and diminished susceptibility to fluconazole or flucytosine must be considered for the management of cryptococcosis.

Fasting blood glucose and insulin sensitivity are unaffected by HAART duration in Cameroonians receiving first-line antiretroviral treatment.

AIMS: This study assessed the relationship between highly active antiretroviral therapy (HAART) duration and cardiometabolic disorders in HIV-infected Cameroonians. METHODS: HIV-infected Cameroonians aged 21 years or above were cross-sectionally recruited at the Yaoundé Central Hospital, a certified HIV care centre, and their anthropometry, body composition (impedancemetry), fasting blood glucose (FBG) and lipid levels, and insulin sensitivity (IS; short insulin tolerance test) were measured. RESULTS: A total of 143 participants with various durations of HAART [treatment-naïve (n=28), 1-13 months (n=44), 14-33 months (n=35) and 34-86 months (n=36)] were recruited. They were mostly women (72%), and had a mean age of 39.5 (SD: 9.8) years. Half (52%) were using a stavudine-containing regimen. There was a significant trend towards a positive change in body mass index and waist-to-hip ratio with increasing duration of HAART (all P=0.02). Systolic (P=0.04) and diastolic (P=0.03) blood pressure, total cholesterol (P=0.01), prevalence of hypertension (P=0.04) and hypercholesterolaemia (P=0.007) were also significantly increased with HAART duration, whereas triglycerides, FBG and IS were unaffected. Clustering of metabolic disorders increased (P=0.02 for ≥1 component of the metabolic syndrome and P=0.09 for ≥2 components) with HAART duration. CONCLUSION: HAART duration is associated with obesity, fat distribution, blood pressure and cholesterol levels in HIV-infected Cameroonians, but does not appear to significantly affect glucose metabolism.

[Lipodystrophy and echographic hepatic steatosis in HIV-positive patients under highly active antiretroviral therapy (HAART) in Yaounde (Cameroon)]. / Lipodystrophie et stéatose hépatique échographique chez les patients VIH positifs sous multithérapie antirétrovirale (ARV) à Yaoundé (Cameroun).

The association between sonographic liver steatosis and clinical lipodystrophy in AIDS patients treated by highly active antiretroviral therapy (HAART) has been studied. We conducted a cross-sectional study reviewing medical files of 117 AIDS patients followed up in Yaounde, Cameroon (6.3 F/1 M, mean age = 40 ± 9.4 years), and treated the patients with HAART protocol comprising stavudine or zidovudine for at least six months. All participants underwent abdominal ultrasonography and anthropometric assessment including body mass index (BMI). Data analysis included determining the association between sonographic liver steatosis, clinical lipodystrophy, and other clinical and biological data using the ¢(2) test, and the calculation of odd ratio. Fifty-one patients presented clinical lipodystrophy. The sonographic prevalence of hepatomegaly and splenomegaly was 70.1% and 25.6%, respectively. The overall prevalence of sonographic steatosis was 28.2%; specifically 37.3% among lipodystrophic patients and 21.1% among nonlipodystrophic patients (P = 0.03). According to the type of lipodystrophy, the prevalence was 40.6% among lipohypertrophic patients, 38.5% among lipodystrophic patients, and 16.7% among lipoatrophic patients. Clinical lipohypertrophy was statistically associated with a higher prevalence of sonographic steatosis (odd ratio = 2.5; 95% CI: [1.01-6.39], and P = 0.04). HAART protocol including stavudine was associated with lipodystrophy. The prevalence of sonographic liver steatosis is high among AIDS patients under HAART and is associated with lipohypertrophy.

High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy.

OBJECTIVES: To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV-infected patients initiating antiretroviral therapy in Cameroon. METHODS: Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti-hepatitis B core (anti-HBc), anti-HCV and - if HBsAg or anti-HCV result was positive or indeterminate - for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6-13.5]. The median HBV viral load was 2.47 x 10(7) IU/mL [interquartile range (IQR) 3680-1.59 x 10(8); range 270 to >2.2 x 10(8)]. Twenty-one patients (12.4%, 95% CI 7.9-18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400-2.06 x 10(6); range 640-5.5 x 10(6)). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [>or=45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49-40.55, P<0.001] and abnormal serum alanine aminotransferase level [>or=1.25 x upper limit of normal (ULN) vs. <1.25 x ULN, OR 7.81, 95% CI 1.54-39.66, P=0.01]; HBV co-infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32-14.17, P=0.02). CONCLUSIONS: These high rates of active HBV and HCV co-infections in HIV-positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV-endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.

Risk factors for HIV-associated neurocognitive disorders (HAND) in sub-Saharan Africa: the case of Yaoundé-Cameroon.

BACKGROUND: The prevalence of HIV-associated neurocognitive disorders (HAND), especially HIV-associated dementia (HAD) is influenced by several risk factors. The prevalence as well as risk factors for HAD are not well known in sub-Saharan Africa (SSA). We have shown that the International HIV Dementia Scale (IHDS) is a useful screening tool for HAND in Yaoundé [Njamnshi AK, Djientcheu VdP, Fonsah JY, Yepnjio FN, Njamnshi DM, Muna WFT. The IHDS is a useful screening tool for HAD/Cognitive Impairment in HIV-infected adults in Yaoundé-Cameroon. Journal of Acquired Immune Deficiency Syndromes 2008;49(4):393-397], but no study in Cameroon has yet investigated the risk factors for HAND or HAD. PATIENTS AND METHODS: A cross-sectional study was conducted in Yaoundé, the capital of Cameroon from September to December 2006. One hundred and eighty-five HIV-positive subjects were included. Diagnosis of HAND was done using the IHDS with a score < or = 10 considered as abnormal. Age, sex, level of education, IV drug use, body mass index (BMI), CDC clinical stage, CD4 counts, hemoglobin levels, administration of highly active antiretroviral therapy (HAART) and type of regimen used, were considered in univariate analysis, with level of significance set at P < or = 0.05. A binary logistic regression was used to determine independent risk factors. RESULTS: The following factors were independent predictors of HAND: advanced clinical stage (OR=7.43, P=0.001), low CD4 count especially CD4 < or = 200 cells/microL (OR=4.88, P=0.045) and low hemoglobin concentration (OR=1.16, P=0.048). CONCLUSION: This first study of the risk factors for HAND in Yaoundé-Cameroon shows findings similar to those described in other studies. These results call for rapid action by policy makers to include HAND prevention strategies such as providing early universal access to HAART based on these risk factors, in the management of HIV patients at risk of HAND in resource-limited settings of SSA like ours.