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BackgroundThe ANRS12286/MOBIDIP trial showed that boosted protease inhibitor (bPI) plus lamivudine dual therapy was superior to bPI monotherapy as maintenance treatment in subjects with a history of M184V mutation.ObjectivesWe aimed to deep analyse the detection of M184V/I variants at time of switch and at the time of virological failure (VF).MethodsUltra-deep sequencing (UDS) was performed on proviral HIV-DNA at inclusion among 265 patients enrolled in the ANRS 12026/MOBIDIP trial, and on plasma from 31 patients experiencing VF. The proportion of M184V/I variants was described and the association between the M184V/I mutation at 1% of threshold and VF was explored with logistic regression models.ResultsM184V and I mutations were detected in HIV-DNA for 173/252 (69%) and 31/252 (12%) of participants, respectively. Longer duration of first-line treatment, higher plasma viral load at first-line treatment failure and higher baseline HIV-DNA load were associated with the archived M184V. M184I mutation was always associated with a STOP codon, suggesting defective virus. The 48 week estimated probability of remaining free from VF was comparable with or without the M184V/I mutation for dual therapy. At failure, M184V and major PI mutations were detected in 1/17 and 5/15 patients in the bPI arm and in 2/2 and 0/3 in the bPI+lamivudine arm, respectively.ConclusionsUsing UDS evidenced that archiving of M184V in HIV-DNA is heterogeneous despite past historical M184V in 96% of cases. The antiviral efficacy of lamivudine-based dual therapy regimens is mainly due to the residual lamivudine activity.

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease. publishedVersion

International audience; APOL1 G1 and G2 alleles have been associated with kidney-related outcomes in people living with HIV (PLHIV) of Black African origin. No APOL1-related kidney risk data have yet been reported in PLHIV in West Africa, where high APOL1 allele frequencies have been observed. Methods: We collected clinical data from PLHIV followed in Burkina Faso (N = 413) and in the ANRS-12169/2LADY trial (Cameroon, Senegal, Burkina Faso, N = 369). APOL1 G1 and G2 risk variants were genotyped using TaqMan assays, and APOL1 high-risk (HR) genotype was defined by the carriage of 2 risk alleles. Results: In West Africa (Burkina Faso and Senegal), the G1 and G2 allele frequencies were 13.3% and 10.7%, respectively. In Cameroon (Central Africa), G1 and G2 frequencies were 8.7% and 8.9%, respectively. APOL1 HR prevalence was 4.9% in West Africa and 3.4% in Cameroon. We found no direct association between APOL1 HR and estimated glomerular filtration rate (eGFR) change over time. Nevertheless, among the 2LADY cohort participants, those with both APOL1 HR and high baseline viral load had a faster eGFR progression (β = −3.9[−7.7 to −0.1] ml/min per 1.73 m2 per year, P < 0.05) than those with low-risk (LR) genotype and low viral load. Conclusion: Overall, the APOL1 risk allele frequencies in PLHIV were higher in the West African countries than in Cameroon, but much lower than previously reported in some Nigeria ethnic groups, which strongly advocates for further investigation in the African continent. This study suggested that the virological status could modulate the APOL1 impact on kidney function, hence reinforcing the need for early therapeutic interventions.

Background The 13-valent pneumococcal conjugate vaccine (PCV13) entered Cameroon’s childhood national immunization programme (NIP) in July 2011 under a 3-dose schedule (6, 10, 14 weeks of age) without any catch-up. We described the impact of PCV13 onserotype distribution among pneumococcal meningitis cases over time. Methods We used laboratory-based sentinel surveillance data to identify meningitis cases among 2- to 59-month-old children with clinically-suspected bacterial meningitis (CSBM) admitted to hospitals in Yaoundé (August 2011-December 2018). Purulent meningitis cases had a cerebrospinal fluid (CSF) white blood cell (WBC) count ≥20 per mm3. Pneumococcal meningitis cases had S. pneumoniae identified from CSF, with serotyping by polymerase chain reaction. Years 2011-2014 were described as early PCV13 era (EPE) and years 2015-2018 as late PCV13 era (LPE) impact periods. Results Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p = 0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0% (31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%). Conclusion Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F; nevertheless, PCV13 VSTs remain common. Because the analyzed surveillance system was not consistent or population based, we could not estimate incidence or overall impact; this emphasizes the need for improved surveillance to document further the utility of PCV13 immunization in Cameroon.

Background Streptococcus pneumoniae S pneumoniae is the main cause of febrile conditions especially among children below two years and the elderly above years old worldwide In Cameroon the frequency of S pneumoniae as the cause of meningitis varied from to from to The aim of this study was to determine the susceptibility to antibiotics of S pneumoniae involved in meningitis nbsp Methods A cross sectional study was carried out during a four year period from April to March Cerebrospinal fluid CSF was collected by clinicians from children less than years with clinically suspected bacterial meningitis at the Mother and Child Center Chantal Biya Foundation MCC CBF in Yaounde A probable case is a suspected clinical case with the CSF showing at least one of the following elements turbid appearance leukocytes ge mm elevated protein gt mg dl or decreased glucose lt mg dl Cases are confirmed when isolates are identified The identification of S pneumoniae was done by soluble antigens the Binax Now reg test Gram stain catalase test optochin test bile solubility and molecular serotyping The antimicrobial susceptibility testing was carried out using the disc diffusion method on Mueller Hinton medium with sheep blood and the minimal inhibitory concentration was found using the Etest reg nbsp Results Out of clinically suspected cases of bacterial meningitis were probable and cases were confirmed Most were isolated in children less than one year old and in boys These incidences occurred mainly during the dry season In the confirmed cases were due to S pneumoniae due to Haemophilus influenzae B due to Neisseria meningitis and due to other germs Among the serotyped pneumococci belonged to serotype A B Of viable isolates of S pneumoniae were resistant to penicillin G and to ceftriaxone nbsp Conclusion S pneumoniae is the main etiology of childhood meningitis in Yaounde The frequency of resistance to penicillin G was high while moderate to ceftriaxone

Background Acute otitis media is a common illness in children under-five years of age and associated with major health care resources in high-income countries. However, there is paucity of data on its epidemiology and clinical presentation in low-income countries. We estimated the prevalence of otitis media and assessed risk factors among children in Cameroon. Methods A community-based cross-sectional prevalence study of otitis media (OM) was performed on randomly selected children aged 2–3 years in Yaounde, Cameroon from March to June 2013. OM was assessed by clinical inspection for chronic suppurative otitis media (CSOM) and tympanometry for otitis media with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than two weeks and OME was defined as a flat ‘type B’ tympanogram. Results Out of 529 children enrolled in the study, 433 (56% males) subjects with available tympanograms were evaluated. Altogether, 9.7% (42/433) of children met the case definition of CSOM, OME or its complications. This consisted of 3 (0.7%) children identified with unilateral CSOM; 7 (1.6%) children with bilateral OME; 31 (7.2%) with unilateral OME and 1 (0.2%) subject with unilateral dry tympanic membrane perforation. Logistic regression analyses showed statistically significant association between OM and parental reporting of “current symptoms of upper respiratory tract infections”, Prevalence Odds Ratio (POR) = 3.71; 95% CI = 1.69–8.14). Conclusion As many as two out of a hundred children between the ages of 2–3 years were affected by significant middle ear disease i.e. CSOM or bilateral OME. These data could be useful as a baseline for estimating the impact of pneumococcal conjugate vaccines (PCV13) introduced in July 2011 for infants in Cameroon.

International audience; OBJECTIVES: High adherence is needed to maintain antiretroviral therapy efficacy. Few attempts at therapeutic patient education (TPE) have been made in sub-Saharan Africa. We describe patients' achievements before intervention and identified needs, TPE programme implementation and evaluation, and patients' satisfaction. METHODS: The TPE programme was proposed to patients in the ANRS-12286/MOBIDIP trial. Beforehand, a directory of competences to manage HIV infection was designed. Patients' HIV-related knowledge and skills assessment was realised, leading to an educational contract. Evaluation was performed using a standardised collection form and a satisfaction survey. RESULTS: Of 154 patients, 146 underwent TPE. During a median of 1.8 years, 47% of patients had >=3 consultations. Educational assessment revealed limited knowledge about HIV disease. Conversely, patients had frequently managed issues of adherence or disclosure. A median of 12 objectives were considered per patient, and 75% were attained. Objectives from the cognitive domain were less frequently attained. Patients appeared satisfied with the intervention: more emphasis was placed on psycho-affective aspects or experience-sharing than on the acquisition of knowledge. CONCLUSION: Active listening, know-how and a space for discussion appear more important for patients than knowledge on disease or treatments. PRACTICE IMPLICATIONS: In HIV care, the directory of learning objectives should be revised to include more objectives concerning practical skills for disease management.

The underpinning theme of the 2016 INTEREST Conference held in Yaoundé, Cameroon, 3–6 May 2016 was ending AIDS as a public health threat by 2030. Focused primarily on HIV treatment, pathogenesis and prevention research in resource-limited settings, the conference attracted 369 active delegates from 34 countries, of which 22 were in Africa. Presentations on treatment optimization, acquired drug resistance, care of children and adolescents, laboratory monitoring and diagnostics, implementation challenges, HIV prevention, key populations, vaccine and cure, hepatitis C, mHealth, financing the HIV response and emerging pathogens, were accompanied by oral, mini-oral and poster presentations. Spirited plenary debates on the UNAIDS 90-90-90 treatment cascade goal and on antiretroviral pre-exposure prophylaxis took place. Joep Lange career guidance sessions and grantspersonship sessions attracted early career researchers. At the closing ceremony, the Yaoundé Declaration called on African governments; UNAIDS; development, bilateral, and multilateral partners; and civil society to adopt urgent and sustained approaches to end HIV by 2030.

International audience; INTRODUCTION:Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings.METHODS:The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study.RESULTS:Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5-9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy.CONCLUSION:HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

International audience; Second-line therapy randomized trials with lopinavir/ritonavir question the value of resistance testing to guide nucleoside reverse transcriptase inhibitor (NRTI) selection. In this study, we investigated the association between baseline drug resistance and treatment outcome after 104 weeks of second-line therapy with NRTIs and either darunavir/ritonavir or lopinavir/ritonavir in West-central Africa. We did an observational analysis of data from 387 individuals in a randomized, open-label 2LADY trial in Burkina Faso, Cameroon, and Senegal. We modeled the association between RTI drug resistance mutations (DRMs) and virological failure (VF) (viral load [VL] \textless50 copies/mL) at week 104 using logistic regressions. Covariates included baseline VL and CD4+ count, demographic, and adherence data. Overall, 193 (49.9%), 150 (38.8%), and 44 (11.4%) individuals had, respectively, low/none (genotypic susceptibility score [GSS] \textless1), intermediate (GSS = 1), and high predicted NRTI activity (GSS \textgreater1) in their prescribed second-line regimen. The average number of DRMs by drug class, the proportion of individuals by GSS category, and the duration of first-line therapy were not associated with VF (p \textgreater .05). High VL at switch was the only consistent prognostic factor for VF after multivariate adjustment (p \textless .01). Suboptimal adherence, high predicted RTI activity, or low NRTI mutations were associated with VF (p \textless .05) when using higher end points for VF or in the intention-to-treat analysis. In conclusion, the use of RTIs with predicted reduced activity does not impair second-line protease inhibitor-based therapy. Therefore, HIV care in resource-limited settings should prioritize strategies to improve adherence and targeted VL testing over drug resistance testing for selecting NRTIs during a protease-based second-line switch.

Background Since antiretroviral therapy (ART), HIV-infected individuals experience mainly non-AIDS-related conditions, among which infectious events are prominent. We aimed to estimate incidence and describe overall spectrum of infectious events, including all grade events, among HIV-1-infected adults failing first-line ART in Yaoundé, Cameroon. Methods All patients from Cameroon enrolled in the second-line ART 2LADY trial (ANRS12169) were included in this secondary analysis. Medical files were reviewed with predefined criteria for diagnosis assessment. Incidence rates (IR) were estimated per 100 person-years (% PY). Results A total of 302 adult patients contributing 840 PY experienced 596 infectious events (IR 71% PY). Only 29 (5%) events were graded as severe. Most frequent infections were upper respiratory tract infections (15% PY), diarrhoea (9% PY) and malaria (9% PY). A total of 369 (62%) infections occurred during the first year (IR 130% PY) followed by a persistent lower incidence during the following 3 years. Higher IR were observed in patients with CD4+ T-cell count ≤200 cells/mm3 for all infectious events except for mycobacterial and parasitic infections. IR of viral, bacterial and parasitic infectious events were lower in case of co-trimoxazole use in patients with CD4+ T-cell count ≤200 cells/mm3. Conclusions Infectious events are common and mainly occur during the first year after treatment initiation. Second-line ART initiation had a positive impact on the entire spectrum of infectious morbidity.

Aims: The main objective of this study was to determine the resistance phenotype of β-lactamines by Klebsiella in three hospitals in Yaounde. Study Design: A cross-sectional descriptive study. Original Research Article Kamga et al.; BMRJ, 9(1): 1-9, 2015; Article no.BMRJ.18250 2 Place and Duration of Study: Bacteriology laboratories of three referrals hospitals in Yaounde (University Teaching Hospital, General Hospital and Gynaeco-Obstetric and Pediatric Hospital) between May and November 2013. Methodology: A cross-sectional descriptive study was carried out over a 6 month-period from May to November 2013 in the bacteriology laboratories of three referrals hospitals in Yaounde. 99 strains of Klebsiella spp. were collected for the study. Antimicrobial susceptibility testing was done using the disc diffusion method. The antibiotics tested were the β-lactams, other inhibitors like clavulanic acid, tazobactam, Ethylene-Diamine-Tetra-Acetic Acid (EDTA), cloxacillin and 3aminophenyl boronic acid hydrochloride. The minimum inhibitory concentration (MIC) was also determined to enable the classification of the different resistance phenotypes. Results: Ninety-nine Klebsiella spp. were identified from urine (52.5%), blood (21.2%), pus (15.2%) and others sites (11.1%). The distribution of the Klebsiella spp. was: Klebsiella pneumoniae pneumoniae (78.7%), Klebsiella oxytoca (12.12%), Klebsiella pneumoniae ozaenae (5.05%), and Klebsiella pneumoniae rhinoscleromatis (4.04%). The isolates were most resistant to piperacillin (76%) and cephalothin, (85%). The most active antibiotics were imipenem (99%), and ertapenem (77%). The phenotypic tests revealed the following resistance phenotypes: extendedspectrum beta-lactamase (30.30%), wild (27.27%), penicillinase resistant to inhibitors (16.16%), carbapenemase (11.11%). Out of these 99 Klebsiella spp., 5 were carbapenemases producers of class C and 6 of class D. The MIC were variable with different antibiotics tested but the MIC of imipenem were always lower than 1 μg/ml. Conclusion: The interpretation of the antimicrobial susceptibility testing has enabled the establishment of a high prevalence of expanded spectrum β-lactamase and consequently leading to an increase in the presence of carbapenemase producing Klebsiella spp. This could lead to therapeutic failure in case of treatment with beta-lactamines antibiotics. Therefore this trend needs to be monitored.

Background Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. Methods and findings In a randomized trial (ANRS 12169), TDF and PI-na ve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddl/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/mu l (IQR: 113-319 cells/mu l). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex ([beta = -10.8 [-18.1,-3.5] for women), age ([beta = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) ((beta = +0.8 [0.1,1.5] per unit of BMI), and study site ((beta = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. Conclusion Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

Background: Cryptococcal meningitis (CM) is a major cause of AIDS-related mortality in Africa. Detection of serum cryptococcal antigen (CrAg) predicts development of CM in antiretroviral (ART) naïve HIV-infected patients with severe immune depression. Systematic pre-ART CrAg screening and pre-emptive oral fluconazole is thus recommended. We postulated that a semi-quantitative CrAg screening approach could offer clinically relevant advantages.Methods: ART-naïve asymptomatic adult outpatients with 160 strongly correlated with proven CM and Biosynex CryptoPS T2-band positivity. During the 1-year follow up period, there was no incident case of CM among screened patients and overall incidence of all-cause mortality was 31.5 per 100 person-years-at-risk (95%CI: 23.0–43.1).Conclusion: HIV-associated asymptomatic cryptococcosis is common in Cameroon, warranting integrated systematic screening and treatment. Biosynex CryptoPS holds promise, at point of care, for rapidly stratifying CrAg positive patients for optimal management including lumbar puncture and combination antifungal therapy when needed.Summary findings: Prevalence of CrAg and meningitis (CM) is high in Cameroon. Biosynex CryptoPS is comparable to IMMY LFA in CrAg screening. Its T2-band correlates with high antigen titres and CM, thus promising for identifying patients requiring effective induction therapy.Note: This study was presented in part at the 10th International Conference on Cryptococcus and Cryptococcosis (ICCC) in Iguazu in Brazil from 26 to 30th March 2017 and won a prize oral presentation.

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART).We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059.Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause).After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

Missed scheduled HIV appointments lead to increased mortality, resistance to antiretroviral therapy, and suboptimum virological response. We aimed to assess whether reminders sent to carers by text message, mobile phone call, or concomitant text message and mobile phone call increase attendance at medical appointments for HIV care in a population of children infected with or exposed to HIV in Cameroon. We also aimed to ascertain the most cost-effective method of mobile-phone-based reminder.MORE CARE was a multicentre, single-blind, factorial, randomised controlled trial in urban, semi-urban, and rural settings in Cameroon. Carers of children who were infected with or had been exposed to HIV were randomly assigned electronically in blocks of four and allocated (1:1:1:1) sequentially to receive a text message and a call, a text message only, a call only, or no reminder (control). Investigators were masked to group assignment. Text messages were sent and calls made 2 or 3 days before a scheduled follow-up appointment. The primary outcomes were efficacy (the proportion of patients attending a previously scheduled appointment) and efficiency (attendance/[measures of staff working time × cost of the reminders]), as a measure of cost-effectiveness. The primary analysis was by intention to treat. This study is registered with the Pan African Clinical Trials Register, number PACTR201304000528276.The study took place between Jan 28 and May 24, 2013. We randomly assigned 242 adult-child (carer-patient) pairs into four groups: text message plus call (n=61), call (n=60), text message (n=60), and control (n=61). 54 participants (89%) in the text message plus call group, 51 (85%) in the call group, 45 (75%) in the text message group, and 31 (51%) in the control group attended their scheduled appointment. Compared with control, the odds ratios for improvement in the primary efficacy outcome were 7·5 (95% CI 2·9-19·0; p0·0001) for text message plus call, 5·5 (2·3-13·1; p=0·0002) for call, and 2·9 (1·3-6·3; p=0·012) for text message. No significant differences were seen in comparisons of the three intervention groups with each other, and there was no synergism between text messages and calls. For the primary efficiency outcome, the mean difference for text message versus text message plus call was 1·5 (95% CI 0·7 to 2·4; p=0·002), for call versus text message plus call was 1·2 (0·7 to 1·6; p0·0001), and for call versus text message was 0·4 (-1·3 to 0·6; p=0·47).Mobile-phone-based reminders of scheduled HIV appointments for carers of paediatric patients in low-resource settings can increase attendance. The most effective method of reminder was text message plus phone call, but text messaging alone was the most efficient (ie, cost-effective) method.No external funding.

Background The aim of the present study was to determine appropriate tenofovir-based regimens meriting evaluation in large-scale randomized trials among sub-Saharan African patients. Methods This was a randomized open-label 96-week prospective pilot study evaluating four first-line regimens: tenofovir/emtricitabine/nevirapine (group 1), tenofovir/ lopinavir/ritonavir (group 2), tenofovir/emtricitabine/zidovudine (group 3) and tenofovir/emtricitabine/efavirenz (group 4) in antiretroviral-naive, HIV-1-infected patients in Senegal and Cameroon. The primary end point was defined as an HIV-1 RNA viral load Results At baseline, 119 patients included were 34% male, had a median plasma viral load of 5.4 log10 copies/ml and median CD4+ T-cell count of 200 cells/mm3 (range 53–358). The primary end point was achieved for groups 1, 3 and 4 (58% [ n=31], 62% [ n=29] and 53% [ n=30], respectively), but not for group 2 (38% [ n=29]). At week 96, undetectable HIV-1 RNA had been achieved in 74% of patients in group 1, 38% in group 2, 72% in group 3 and 73% in group 4. Patients with detectable HIV-1 RNA at week 16 were more likely to have baseline HIV-1 RNA≥100,000 copies/ml (adjusted OR 5.56, 95% CI 1.72, 16.67). HIV mutations associated with protease inhibitor resistance emerged in three patients, all of whom were in group 2. Anaemia occurred in two group 3 patients and was the only serious treatment-related adverse event. Conclusions Three efficient and safe tenofovir-based triple regimens were identified; the two-drug regimen (tenofovir/lopinavir/ritonavir) did not achieve the protocol-defined virological threshold of efficacy.

Summary Background In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. Methods The randomised, controlled, non-inferiority Stratall trial was done in a decentralised setting in Cameroon. Between May 23, 2006, and Jan 31, 2008, ART-naive adults were randomly assigned (1:1) to clinical monitoring (CLIN) or viral load and CD4 cell count plus clinical monitoring (LAB) and followed up for 24 months. We calculated costs, number of life-years saved (LYS), and incremental cost-effectiveness ratios (ICERs) with data from patients who had been followed up for at least 6 months. We considered two cost scenarios in which viral load plus CD4 cell count tests cost either US$95 (scenario 1; Abbott RealTime HIV-1 assay) or $63 (scenario 2; generic assay). We compared ICERs with a WHO-recommended threshold of three times the per-person gross domestic product (GDP) for Cameroon ($3670–3800) and an alternative lower threshold of $2385 to determine cost-effectiveness. We assessed uncertainty with one-way sensitivity analyses and cost-effectiveness acceptability curves. Findings 188 participants who underwent LAB and 197 who underwent CLIN were followed up for at least 6 months. In scenario 1, LAB increased costs by a mean of $489 (SD 430) per patient and saved 0·103 life-years compared with CLIN (ICER of $4768 [95% CI 3926–5613] per LYS). In scenario 2, the incremental mean cost of LAB was $343 (SD 425) —ie, an ICER of $3339 (2507–4173) per LYS. A combined strategy in which LAB would only be used in patients starting ART with a CD4 count of 200 cells per μL or fewer suggests that 0·120 life-years would be saved at an additional cost of $259 per patient in scenario 1 (ICER of $2167 [95% CI 1314–3020] per LYS) and $181 in scenario 2 (ICER of $1510 [692–2329] per LYS) when compared with CLIN. Interpretation Laboratory monitoring was not cost effective in 2006–10 compared with clinical monitoring when the Abbott RealTime HIV-1 assay was used according to the $3670 cost-effectiveness threshold (three times per-person GDP in Cameroon), but it might be cost effective if a generic in-house assay is used. Funding French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and Ensemble pour une Solidarite Therapeutique Hospitaliere En Reseau (ESTHER).

Background: In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses, and inform decisions. Methods: We pooled data from 13 research cohorts in 5 sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire, and Senegal) and 2 Asian (Cambodia and Laos) countries. HIV-infected adults (18 years and older) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results: Overall 3917 adults (62% women) on ART were followed up during 10,154 person-years. In the

OBJECTIVES: Many people living with HIV/AIDS in resource-limited settings begin antiretroviral therapy (ART) at low CD4 counts. Here we investigated the simultaneous effect of individual- facility- and regional-level factors on late ART initiation. METHODS: We conducted a survey in a nationally representative sample of 55 HIV treatment facilities in Cameroon. Medical records of 4935 patients >15 years of age who initiated ART in the month of October during the period 2007-10 were reviewed to gather individual characteristics. Late ART initiation was defined as CD4 count

Background To investigate change in renal function in African patients initiating second-line antiretroviral therapy (ART) including ritonavir-boosted protease inhibitor (PI/r) with or without tenofovir disoproxil fumarate (TDF). Methods HIV-1-positive adults, failing standard first-line ART were randomized to either TDF/emtricitabine (FTC)+LPV/r, abacavir + didanosine +LPV/r or TDF/FTC+ darunavir (DRV)/r and followed for 18 months. Patients with an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 at baseline were included in this analysis. Results Data from 438 out of 454 randomized patients were analysed. Median age was 38 years and 72% were women. Initiation of PI/r-based second-line regimen induced a marked eGFR decline of -10.5 ml/min/1.73 m2 at week 4 in all treatment groups with a greater decrease in TDF/FTC+LPV/r arm (-15.1 ml/min/1.73 m2). At month 18, mean eGFR in the non-TDF containing regimen recovered its baseline level and was significantly greater than eGFR 18-month levels in the TDF-containing regimens that experienced only partial recovery (difference: -10.7; CI -16.8, -4.6; P=0.001 in TDF/FTC+LPV/r and -6.4; CI -12.5, -0.3; P=0.04 in TDF/FTC+DRV/r). At 18 months, prevalence of stage 3 chronic kidney disease was low (Conclusions Overall, these results suggest a reasonable renal tolerance of a regimen associating TDF/FTC+PI/r in African patients with eGFR>60 ml/ml/1.73 m2 at baseline. They also support the recommendation of reassessing renal function 1 month after initiation of treatment including ritonavir to account for the ritonavir-related artefactual decrease of eGFR and determine the new reference baseline value.

Objective Patients infected with HIV have a direly increased risk of developing pulmonary hypertension (PH), and of dying from the condition. While Africa carries the greatest burden of HIV infection worldwide, there is unclear data summarising the epidemiology of PH among HIV-infected people in this region. Our objective was to determine the prevalence and incidence of PH among HIV-infected people living across Africa. Design A systematic review and meta-analysis. Participants HIV-infected African people residing in Africa. Outcome Prevalence and incidence of PH diagnosed through echocardiography or right heart catheterisation. Data sources Articles published in PubMed/MEDLINE, EMBASE, African Journals Online and African Index Medicus between 1 January 1980 and 30 June 2016, without any language restriction. Results Overall, 121 studies were screened; 3 were included in this review: 1 from Southern Africa (South Africa), 1 from Eastern Africa (Tanzania) and 1 from Central Africa (Cameroon). These studies included HIV-infected adult patients selected based on presentation with cardiovascular symptoms. No study reported PH incidence or PH incidence/prevalence among children and adolescents. The quality assessment yielded moderate risk of bias. Ages of participants ranged between 18 and 78 years, and the proportion of females varied between 52.3% and 68.8%. The prevalence of PH in the pooled sample of 664 patients was 14% (95% CI 6%–23%). Limitations Only 3 studies were found eligible from 3 regions of the African continent. Conclusions The prevalence of PH among HIV-infected people in Africa seems very high. Further studies are urgently warranted to determine the incidence of HIV-induced PH, which must include all subregions of Africa. Trial registration number Review registration number PROSPERO CRD42016033863.

Introduction. Community-acquired urinary tract infections (CAUTIs) are usually treated empirically. Geographical variations in etiologic agents and their antibiotic sensitivity patterns are common. Knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Our aim was to determine the major bacterial etiologies of CAUTIs and their antibiotic resistance patterns in a cosmopolitan area of Cameroon for comparison with prescription practices of local physicians.Methods. We performed a cross-sectional descriptive study at two main hospitals in Yaoundé, collecting a clean-catch mid-stream urine sample from 92 patients having a clinical diagnosis of UTI. The empirical antibiotherapy was noted, and identification of bacterial species was done on CLED agar; antibiotic susceptibility testing was performed using the Kirby-Bauer disc diffusion method.Results. A total of 55 patients had samples positive for a UTI. Ciprofloxacin and amoxicillin/clavulanic acid were the most empirically prescribed antibiotics (30.9% and 23.6%, resp.); bacterial isolates showed high prevalence of resistance to both compounds.Escherichia coli(50.9%) was the most common pathogen, followed byKlebsiella pneumoniae(16.4%). Prevalence of resistance for ciprofloxacin was higher compared to newer quinolones.Conclusions.E. coliandK. pneumoniaewere the predominant bacterial etiologies; the prevalence of resistance to commonly prescribed antibiotics was high.

Introduction Recently published large randomized controlled trials, START, TEMPRANO and HPTN 052 show the clinical benefit of early initiation of antiretroviral treatment (ART) in HIV-infected persons and in reducing HIV transmission. The trials influenced the World Health Organization (WHO) decision to issue updated recommendations to prescribe ART to all individuals living with HIV, irrespective of age and CD4 cell count. Discussion It is clear that the new 2015 WHO recommendations if followed, will change the face of the HIV epidemic and probably curb its burden over time. Implementation however, requires that health systems, especially those in low and middle-income settings, be ready to face this challenge on a large scale. HIV prevention and treatment are easy in theory yet hard in practice. The new WHO guidelines for initiation of ART regardless of CD4 cell count will lead to upfront increases in the costs of healthcare delivery as the goal is to treat all those now newly eligible for ART. Around 22 million people living with HIV qualify and will therefore require ART. Related challenges immediately follow: firstly, that everyone must be tested for HIV; secondly, that anyone who has had an HIV test should know their result and understand its significance; and, thirdly, that every person identified as HIV-positive should receive and remain on ART. The emergence of HIV drug resistant strains when treatment is started at higher CD4 cell count thresholds is a further concern as persons on HIV treatment for longer periods of time are at increased risk of intermittent medication adherence. Conclusions The new WHO recommendations for ART are welcome, but lacking as they fail to consider meaningful solutions to the challenges inherent to implementation. They fail to incorporate actual strategies on how to disseminate and adopt these far-reaching guidelines, especially in sub-Saharan Africa, an area with weak healthcare infrastructures. Well-designed, high-quality research is needed to assess the feasibility, safety, acceptability, impact, and cost of innovations such as the universal voluntary testing and immediate treatment approaches, and broad consultation must address community, human rights, ethical, and political concerns. Electronic supplementary material The online version of this article (doi:10.1186/s40249-016-0179-9) contains supplementary material, which is available to authorized users.

PURPOSE OF REVIEW: Given the lack of evidence on how to best design and implement antiretroviral therapy (ART) scaling-up policies operational research has seen a surge in interest. There is however little published information on the contribution of operational research in ART programs implementation or in improvement of associated outcomes. The article focuses therefore on how operational research may contribute to such improvements and what the key enabling factors are for its integration into program frameworks. RECENT FINDINGS: One of the most systematic operational research linked to a national ART program on the African continent was conducted in Cameroon between 2006 and 2010. Along with operational research carried out elsewhere in Africa it helped demonstrate that a strategy of decentralizing HIV care can increase treatment coverage and improve early access to care while maintaining good clinical outcomes. Multipartnership between local researchers national authorities healthcare professionals and the civil society is the key enabling factor for the relevance of operational research and the translation of its results into policy and practice. SUMMARY: In spite of a dramatic increase in access to ART during recent years in low-income countries the fight against HIV remains a failure in terms of the goal of breaking the pandemic dynamic. Operational research is needed more than ever to face this challenge.

Background Good knowledge in HIV care among physicians is a necessary prerequisite to effective antiretroviral therapy (ART) scaling-up in Sub-Saharan Africa. Methods Between September 2006 and March 2007, a 27-item knowledge questionnaire was proposed to all HIV physicians working in 27 hospitals throughout six provinces of Cameroon. Physicians’ responses were compared between the three levels of decentralization of the Cameroonian healthcare delivery system (χ2 and Fisher tests). Correct responses were summed to build a knowledge score. Factors significantly associated with a higher score were identified using linear regression. Results In total, 93 physicians filled in the questionnaire. Level of knowledge was globally good (median score 23), with no significant difference between the three levels of decentralization. Gaps in knowledge were observed regarding the use of cotrimoxazole and the follow-up of ART-treated patients. Main factors independently associated with a higher knowledge score included training, involvement in therapeutic committees, satisfactory collaboration with other practitioners and establishment of strong relationships between patients and patients’ associations. Conclusions Overall knowledge in HIV care is good among HIV physicians working at all three levels of decentralization of healthcare in Cameroon. However, a national training policy should be set up to improve knowledge and practices in both ART follow-up and specific situations such as paediatric HIV. Collaboration between caregivers and external resources involved in HIV care should also be encouraged.

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 × 107 IU/mL [interquartile range (IQR) 3680–1.59 × 108; range 270 to >2.2 × 108]. 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 × 106; range 640–5.5 × 106). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [≥45 years vs.

Cameroon has initiated a national programme of HIV care decentralization providing access to antiretroviral therapy (ART) for patients with CD4 cell counts less than 200 cells/microl or AIDS stage. Current clinical research suggests these criteria may be too stringent. This study aimed at evaluating the effect of not receiving ART on patients' psychosocial outcomes.The national cross-sectional survey EVAL (ANRS 12-116) collected psychosocial and clinical data for 3151 patients attending HIV services (September 2006 to March 2007).Propensity score matching was used to control for demographic/clinical-immunological differences between patients receiving ART and those who did not. Generalized linear models were used to assess the impact, for different CD4 cell levels, of "not receiving" ART on health-related quality of life (HRQoL) inconsistent condom use with a sexual partner either serodiscordant or of unknown HIV status, self-reported symptoms and disclosure of HIV status to relatives or friends.Seventy-eight per cent of patients included in the survey were receiving ART. Non-treated patient breakdown was as follows: 8% (CD4200 or AIDS stage), 5% (200or=CD4or=350) and 8% (CD4350). In the multivariate matched-pairs analysis, impaired physical HRQoL, more frequent inconsistent condom use, more self-reported symptoms and less frequent disclosure of HIV status were all significantly associated (P0.0001) with not receiving ART, irrespective of the CD4 cell level.In addition to increasing clinical effectiveness, earlier initiation of ART at less severe immune-depression levels than previously recommended by World Health Organization guidelines for low-resource settings may be justified for improving subjective health and positive prevention among people living with HIV.

Objective Our study aimed at estimating the prevalence of inconsistent condom use and at identifying its determinants in steady partnerships among people living with HIV/AIDS (PLWHA) in Cameroon. Methods Analyses were based on data collected during the national cross-sectional multicentre survey EVAL (ANRS 12-116), which was conducted in Cameroon between September 2006 and March 2007 among 3151 adult PLWHA diagnosed HIV-positive for at least 3 months. The study population consisted of the 907 survey participants who reported sexual activity during the previous 3 months, with a steady partner either HIV-negative or of unknown HIV status. Logistic regression was used to identify factors associated with individuals9 report of inconsistent condom use during the previous 3 months. Results Inconsistent condom use was reported by 35.3% of sexually active PLWHA. In a multivariate analysis adjusted for socio-demographic characteristics, not receiving antiretroviral therapy (OR (95% CI): 2.28 (1.64 to 3.18)) was independently associated with inconsistent condom use. Conclusions The prevalence of unsafe sex remains high among sexually active PLWHA in Cameroon. Treatment with antiretroviral therapy is identified as a factor associated with safer sex, which further encourages the continuation of the national policy for increasing access to HIV treatment and care, and underlines the need to develop counselling strategies for all patients.

To study the impact of both decentralization of HIV care and individual factors on delayed first consultation (or =6 months) after HIV diagnosis in Cameroon, in the context of the national antiretroviral treatment scale-up program.The national cross-sectional multicenter survey EVAL (ANRS 12-116) was conducted from September 2006 to March 2007 in 27 HIV centers in Cameroon.: Logistic regression was used to characterize patients with delayed first consultation among 3151 HIV-infected adults.Fifteen percent of patients reported a delay of at least 6 months before their first consultation after HIV diagnosis. In the multivariate analysis adjusted for the frequency of visits to the HIV center, independent correlates of reporting a delay of at least 6 months before consulting included the characteristics of the HIV centers (created before 2005 and located in small or medium-size hospitals) and the following individual patient characteristics: sex and matrimonial status (women living in a couple), the circumstances of the HIV diagnosis (test not performed in the hospital providing HIV care, test performed during a voluntary screening campaign) and patient's negative perception of antiretroviral treatment toxicity.Delays before first consultation for HIV care in Cameroon have been reduced, thanks to the full implementation of the national program of decentralization. Results underline the importance of coordinating diagnosis with treatment activities and the need to develop counseling actions, focusing on the balance between antiretroviral treatment effectiveness and its potential side effects. Counseling should also be part of patients' follow-up after diagnosis during voluntary screening campaigns.

A cross-sectional study, performed at a routine human immunodeficiency virus (HIV)/AIDS clinic in Cameroon that uses the World Health Organization public health approach, showed low rates of virological failure and drug resistance at 12 and 24 months after initiation of antiretroviral therapy. Importantly, the cross-sectional study also showed that the World Health Organization recommendation for second-line treatment would be effective in almost all patients with HIV drug resistance mutations.

The objective of this study was to identify factors associated with HIV infection among specific population subgroups and complement the HIV surveillance system in Cameroon. Five subgroups (truck drivers, female-sex-workers, university students, health service providers, and residents along Chad-Cameroon petroleum pipeline) were targeted in 2004. Potential participants were approached at their geographically diverse areas and consented to participate in the study. Anonymous blood samples were collected. 4,011 participants were surveyed (35% students, 25% sex-workers, 20% pipeline residents, 12.5% health service providers, 7.5% truck drivers). HIV prevalence was highest among sex-workers [26.4%, (95% CI, 23.6-29.2)], pipeline residents [19.9% (95% CI, 17.1-22.7)] and truck drivers [16.3% (95% CI, 12.3-20.9)] and lowest among health service providers [5.2% (95% CI, 3.4-7.5)] and university students [3.8% (95% CI, 2.9-5.0)]. Risky sexual behaviours were practiced in all subpopulations. Multivariable analysis shows in female-sex-workers that; older age, residing in the grassland region (Northwest and West Provinces) and inconstant condom use were significantly associated with HIV infection. Despite a moderate HIV prevalence in the general Cameroonian population, some subgroups are at much higher risk for HIV transmission and practicing risky sexual behaviours. There is need for expanded prevention and care programs with emphasis on truck drivers, sex-workers and pipeline residents.

The development of HIV related pulmonary arterial hypertension (PAH) reduces the probability of survival by half as compared with HIV-infected individuals without HIV related PAH. HIV infected patients have a greater incidence of PAH compared to general population and have a 2500-fold increased risk of developing PAH. It is therefore important to have a recent overview of the problem in Africa, the most HIV affected part of the world (70 % of all HIV infection in the world). First, we discussed the epidemiology of HIV-related PAH in Africa. Second, the current understanding of the HIV-related PAH pathogenesis has been covered. Third, role of highly active antiretroviral therapy on HIV-related PAH has been revisited. There are few data concerning epidemiology of HIV related pulmonary hypertension in Africa leading to necessity to conduct further prospective large studies. The prevalence of PAH among HIV infected people in Africa varies from 5 to 13 %. The prevalence of HIV-related PAH in Africa is notably high compared to those in developed countries and in general population. The pathogenesis of PAH is clearly complex, and probably results from the interaction of multiple modulating genes with environmental factors. The physiopathology includes cytokines secretion increase which induces dysregulation of endothelial and vascular smooth muscle cell growth and imbalance of endogenous vasodilators and constrictors; HIV viral proteins which induces vascular oxidative stress, smooth myocyte proliferation and migration, and endothelial injury and genetic predisposition due to some major histocompatibility complex alleles, particularly HDL-DR6 and HLA-DR5. Histologically, HIV related PAH has the same characteristics with other types PAH. Antiretroviral therapy have a beneficial effect on the outcome of HIV related pulmonary hypertension, but it lacks evidence from large prospective studies.

Introduction : It is estimated that 150 million urinary tract infections (UTIs) occur yearly worldwide, resulting in more than 6 billion dollar in direct healthcare cost. The etiology of UTIs is predictable, with Escherichia coli , an Enterobacteriaceae being the principal pathogen. Quinolones are usually the drug of choice. In this study, we report the resistance pattern of Enterobacteriaceae isolates from UTIs to quinolones among in-patients and out-patients at the Yaounde Reference Hospital in Cameroon. Methods : A cross-sectional descriptive study was carried out for a ten-month period. Consecutive clean-catch mid-stream urine samples were collected from 207 in and out-patients. Identification was done using the Api 20E, and susceptibility testing using the Kirby Bauer’s disc diffusion method and the MIC was done using the E-test. Results : Out of the 207 isolates, 58(28.0%) were found to be resistant to all the quinolones used in the study. The resistances observed by species were in the order: Enterobacte r 4(30.8%); Klebsiella 19(29.7%); Escherichia 25 (29.4%); Proteus 2(11.8%); Serratia 4(25.0%). Quinolone resistance for Escherichia was 42.9% for In-Patients (IP) and 16.3% for Out-Patient (OP) (P-value = 0.006); Klebsiella 35.9% for IP and 20% for OP; Proteus 11.1% for IP and 12.5% for OP; Serratia 18.2% for IP and 40% for OP; Enterobacter 22.2 for IP and 50% for OP. Conclusion : High resistance rates to quinolones were observed not only for in-patients but also for out-patients with urinary tract enterobacterial infections. These findings demonstrate the importance of antibiotics susceptibility testing in improving quinolones prescription practices in Cameroon.

Background: Knowledge of the characteristics of patients co-infected with tuberculosis (TB) and human immunodeficiency virus (HIV) when TB treatment is initiated would allow clinicians to improve care and help policy-makers develop relevant and realistic guidelines. The aim of this study was to describe socio-demographic, clinical, and laboratory characteristics of TB/HIV co-infected patients starting inpatient TB treatment in Yaounde, Cameroon. Methods: We conducted a retrospective cross-sectional study, collecting data from medical records of HIV-infected patients with TB, aged 15 years old or more, hospitalized in the Infectious Diseases Unit of the Yaounde Central Hospital, Cameroon from January 1, 2006 to June 30, 2013. Results: The mean age of 337 patients meeting study inclusion criteria was 39.3 years. More than half were female (53.4%). Most (89.3%) resided in urban areas, 44.2% had a secondary education, and 46.0% were married. The majority was receiving co-trimoxazole prophylaxis (79.5%), and two thirds were taking antiretroviral therapy (67.4%). The mean duration of known HIV infection before TB treatment was 8.4 months. Most (88.1%) had newly diagnosed TB, rather than relapsed disease. Smear-positive pulmonary TB was documented in a third, (35.3%). Laboratory data revealed a median white blood cell count of 5,100 cells/mm 3 (IQR 3,300-7,990 cells/mm 3 ), a median hemoglobin level of 8 g/dl (IQR 7–10 g/dl), and a median CD4 cell count of 102 cells/mm 3 (IQR 33–178 cells/mm 3 ). Sex differences in our study included older age in the men (p < 0.001), more of whom were married (p < 0.001) and had achieved a higher level of education (p = 0.042). Men had fewer diagnoses of smear-positive pulmonary TB (p = 0.020). They weighed more than the women (p = 0.001) and had higher hemoglobin levels (p =0 .003). Conclusions: Suboptimal adherence to WHO treatment recommendations in our Cameroonian study reinforces the importance of prescribing co-trimoxazole in HIV infection and ART for all TB/HIV co-infected persons. We urge that Ministries of Health continue implementing and disseminating guidelines for management of TB/HIV co-infected patients, and we call for measures ensuring that healthcare facilities’ stocks of ART and co-trimoxazole are sufficient to meet the need for both.

International audience; BACKGROUND:Evidence of gender differences in antiretroviral treatment (ART) outcomes in sub-Saharan Africa is conflicting. Our objective was to assess gender differences in (1) adherence to ART and (2) virologic failure, immune reconstitution, mortality, and disease progression adjusting for adherence.METHODS:Cohort study among 459 ART-naive patients followed up 24 months after initiation in 2006-2010 in 9 rural district hospitals. Adherence to ART was assessed using (1) a validated tool based on multiple patient self-reports and (2) antiretroviral plasma concentrations. The associations between gender and the outcomes were assessed using multivariate mixed models or accelerated time failure models.RESULTS:One hundred thirty-five patients (29.4%) were men. At baseline, men were older, had higher body mass index and hemoglobin level, and received more frequently efavirenz than women. Gender was not associated with self-reported adherence (P = 0.872, 0.169, and 0.867 for moderate adherence, low adherence, and treatment interruption, respectively) or with antiretroviral plasma concentrations (P = 0.549 for nevirapine/efavirenz). In contrast, male gender was associated with virologic failure [odds ratio: 2.18, 95% confidence interval (CI): 1.31 to 3.62, P = 0.003], lower immunologic reconstitution (coefficient: -58.7 at month 24, 95% CI: -100.8 to -16.6, P = 0.006), and faster progression to death (time ratio: 0.30, 95% CI: 0.12 to 0.78, P = 0.014) and/or to World Health Organization stage 4 event (time ratio: 0.27, 95% CI: 0.09 to 0.79, P = 0.017).CONCLUSIONS:Our study provides important evidence that African men are more vulnerable to ART failure than women and that the male vulnerability extends beyond adherence issues. Additional studies are needed to determine the causes for this vulnerability to optimize HIV care. However, personalized adherence support remains crucial.

To propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.We used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d'Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.In Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007-2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).The estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.Proposer deux nouveaux indicateurs pour évaluer l'accès au traitement antirétroviral (TAR) contre le virus de l'immunodéficience humaine (VIH): (i) le délai entre la séroconversion au VIH et le début du TAR, et (ii) le délai entre l'éligibilité au TAR et le début du TAR, appelé «délai écoulé avant le début du TAR». Estimer l'utilité de ces indicateurs au Cameroun.Nous avons utilisé une régression linéaire pour modéliser le déclin naturel au fil du temps du nombre de lymphocytes T CD4+ (cellule CD4+) chez les individus infectés par le VIH. Le modèle a été conçu à l'aide de données provenant d'une cohorte de 351 individus de Côte d'Ivoire. Nous l'avons utilisé pour estimer le délai entre la séroconversion et le début du TAR ainsi que le retard dans l’accès au TAR sur un échantillon représentatif de 4154 individus infectés par le VIH ayant commencé un TAR au Cameroun entre 2007 et 2010.Au Cameroun, le taux médian de CD4+ au début du TAR est passé de 140 cellules 140 cellules/μl (intervalle interquartile, IQR: de 66 à 210) en 2007–2009 à 163 cellules/μl (IQR: de 73 à 260) en 2010. Le délai moyen estimé entre la séroconversion et le début du TAR est passé de 10,4 années (intervalle de confiance, IC, à 95%: de 10,3 à 10,5) à 9,8 années (IC à 95%: de 9,6 à 10,0). Le retard dans l’ accès au TAR est passé de 3,4 années (IC à 95%: de 3,1 à 3,7) à 5,8 années (IC à 95%: de 5,6 à 6,2).Les estimations du délai entre la séroconversion et le début du TAR et du retard dans l’accès au TAR indiquent que les progrès accomplis au Cameroun sont insuffisants. Ces indicateurs devraient aider à évaluer l'efficacité des interventions de santé publique visant à accélérer l’accès au TAR .Proponer dos nuevos indicadores para monitorear el acceso al tratamiento antirretroviral (TAR) para el virus de la inmunodeficiencia humana (VIH); (i) el tiempo desde la seroconversión del VIH al inicio del TAR, y (ii) el tiempo desde la elegibilidad del TAR al inicio del mismo, referido como retraso en el inicio del TAR. Estimar los valores de estos indicadores en Camerún.Se utilizó la regresión lineal para modelizar la disminución natural de la cantidad de linfocitos T CD4+ (célula CD4+) en los individuos infectados por el VIH con el tiempo. El modelo se adaptó utilizando datos de una cohorte de 351 individuos en Côte d’Ivoire. Se utilizó el modelo para estimar el tiempo entre la seroconversión y el inicio del TAR y el retraso en el inicio del TAR en una muestra representativa de 4.154 individuos infectados por el VIH que iniciaron el TAR en Camerún entre 2007 y 2010.En Camerún, la media del recuento de células CD4+ en el inicio del TAR creció de 140 células/μl (rango intercuartílico, RIC: de 66 a 210) en 2007-2009 a 163 células/μl (RIC: de 73 a 260) en 2010. El tiempo medio estimado desde la seroconversión hasta el inicio del TAR descendió de 10,4 años (intervalo de confianza, IC, del 95%: de 10,3 a 10,5) a 9,8 años (IC del 95%: de 9,6 a 10,0). El retraso en el inicio del TAR aumentó de 3,4 años (IC del 95%: de 3,1 a 3,7) a 5,8 años (IC del 95%: de 5,6 a 6,2).El tiempo estimado para iniciar el TAR y el retraso en el inicio del TAR indican que el progreso en Camerún es insuficiente. Estos indicadores deberían ayudar a monitorizar si las intervenciones de salud pública para acelerar el inicio del TAR son eficaces.اقتراح مؤشرات جديدة لمراقبة الحصول على علاج باستخدام مضادات الفيروسات القهقرية (ART) لمقاومة فيروس عوز المناعة البشري (HIV)؛ (1) الفترة الزمنية منذ انقلاب تفاعلية مصل HIV (ظهور أجسام مضادة له) حتى بدء ART، و(2) الفترة الزمنية منذ التأهل لـ ART حتى البدء فيه، والمشار إليه بالتأخر في بدءART . وتقييم القيم التي تم التوصل إليها بفضل هذه المؤشرات في الكاميرون.استخدمنا أسلوب التحوف الخطي للوصول إلى نموذج للانخفاض الطبيعي في أعداد الخلايا اللمفية التائية من فئة CD4+ (خلايا فئة CD4+ ) في الأشخاص المصابين بمرض عوز المناعة البشري مع مرور الوقت. وكان النموذج مناسبًا للغرض بفضل استخدام بيانات تم الحصول عليها من مجموعة من الأشخاص يبلغ عددهم 351 شخصًا في كوت ديفوار. وقد استخدمنا هذا النموذج لتقدير الفترة بين انقلاب تفاعلية المصل وبدءART من ناحية وتقدير فترة التأخر في بدء ART من ناحية أخرى، وذلك في عينة تمثل المرضى تشمل 4154 مصابًا ممن بدأواART في الكاميرون في الفترة بين 2007 و2010.زاد في الكاميرون وسيط القيمة لتعداد الخلايا فئة CD4+ عند بدء ART من 140 خلية/ميكرو لتر (المدى الربيعي: 66 إلى 210) في الفترة من 2007 – 2009 إلى 163 خلية/ميكرو لتر (المدى الربيعي: 73 إلى 260) في عام 2010. وانخفض متوسط الفترة الزمنية منذ انقلاب تفاعلية المصل حتى بدءART من 10.4 عام (بنسبة أرجحية مقدارها 95%: 10.3 إلى 10.5) إلى 9.8 عام (بنسبة أرجحية مقدارها 95%: 9.6 إلى 10.0). وزاد التأخر في بدء ART من 3.4 عام (بنسبة أرجحية مقدارها 95%: 3.1 إلى 3.7) إلى 5.8 عام (بنسبة أرجحية مقدارها 95%: 5.6 إلى 6.2).تشير الفترة الزمنية المقدرة لبدء ART وللتأخر في بدء ART إلى أن التقدم في العلاج في الكاميرون لا يفي بالاحتياجات. ومن المفترض أن تساعد هذه المؤشرات على مراقبة إذا ما كانت التدخلات في مجال الصحة العامة للإسراع ببدء ART ناجحة بالفعل.为监控人类免疫缺陷病毒 (HIV) 的抗逆转录病毒治疗 (ART) 情况而提出两个新指标；(i) 从 HIV 血清转化到 ART 开始的时间，和 (ii) 从 ART 合格到开始的时间，也称为 ART 开始时间延迟。 旨在评价喀麦隆境内这些指标值。.我们用线性回归法建立了 HIV 感染者体内的 CD4+ T 淋巴细胞（CD4+ 细胞）数在一段时间内呈自然递减的模型。 该模型拟合从科特迪瓦境内 351 名人员中采集的数据。 我们以在喀麦隆境内于 2007 年至 2010 年期间接受 ART 的 4154 名 HIV 患者为代表性样本，采用该模型来估计血清转化到 ART 开始的时间以及 ART 开始时间的延迟。.在喀麦隆境内，ART 开始时的 CD4+ 细胞计数中值从 2007 年至 2009 年的 cells/μl（四分位差：IQR： 66 至 210）增加至 2010 年的 163 cells/μl（IQR： 73 至 260）。从血清转化到 ART 开始的估计平均时间从 10.4 年（95% 置信区间，CI： 10.3 至 10.5）下降至 9.8 年（95% CI： 9.6 至 10.0）。 ART 的开始时间延迟从 3.4 年（95% CI： 3.1 至 3.7）增加至 5.8 年（95% CI： 5.6 至 6.2）。.开始 ART 的预计时间和 ART 开始时间的延迟表明喀麦隆境内并未取得足够的进步。 这些指标应有助于监控公共卫生干预措施是否能够成功加快 ART 的开始时间。.Предложить два новых показателя для контроля доступности антиретровирусной терапии (АРВТ), предназначенной для лечения вируса иммунодефицита человека (ВИЧ): (i) время от сероконверсии ВИЧ до начала АРВТ и (ii) время с момента определения соответствия пациента критериям назначения АРВТ до начала терапии, называемое задержкой начала АРВТ. Оценить значения данных показателей в Камеруне.Было смоделировано естественное снижение с течением времени числа T-лимфоцитов CD4+ (клеток CD4+) у инфицированных ВИЧ при помощи линейной регрессионной модели. Модель корректировалась с использованием данных когорты из 351 человека в Кот-д’Ивуаре. Модель применялась для оценки временного отрезка между сероконверсией и началом АРВТ, а также задержки начала АРВТ в репрезентативной выборке из 4154 ВИЧ-инфицированных, начавших АРВТ в Камеруне в период между 2007 и 2010 гг.В Камеруне медианное число клеток CD4+ в начале АРВТ увеличилось с 140 клеток/μл (межквартильный размах, МКР: 66–210) в 2007–2009 гг. до 163 клеток/μл (МКР: 73–260) в 2010 г. Выявленное среднее время от сероконверсии до начала АРВТ сократилось с 10,4 года (95% доверительный интервал, ДИ: 10,3–10,5) до 9,8 года (95% ДИ: 9,6–10,0). Задержка начала АРВТ увеличилась с 3,4 года (95% ДИ: 3,1–3,7) до 5,8 года (95% ДИ: 5,6–6,2).Полученные значения времени начала АРВТ и задержки начала АРВТ указывают на недостаточный прогресс в Камеруне. Эти показатели должны помочь в оценке успешности мероприятий в области здравоохранения, направленных на ускорение начала АРВТ.

International audience; OBJECTIVE:WHO recommends ritonavir-boosted protease inhibitor with two nucleoside reverse transcriptase inhibitors in HIV-infected patients failing non-nucleoside reverse transcriptase inhibitor-based first-line treatment. Here, we aimed to provide more evidence for the choice of nucleoside reverse transcriptase inhibitor and boosted protease inhibitor.DESIGN:ANRS 12169 is a 48-week, randomized, open-label, non-inferiority trial in three African cities, comparing efficacy and safety of three second-line regimens.METHODS:Patients failing non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy with confirmed plasma HIV-1 viral load above 1000 copies/ml were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (control group as per WHO recommendations), abacavir + didanosine + lopinavir/ritonavir (ABC/ddI group) or tenofovir/emtricitabine + darunavir/ritonavir (DRV group) regimens. The primary endpoint was the proportion of patients with plasma vral load below 50 copies/ml at week 48 in the modified intention-to-treat population. Non-inferiority was pre-specified with a 15% margin.RESULTS:Of the 454 randomized patients, 451 were included in the analysis. Globally, 294 (65.2%) and 375 (83.2%) patients had viral load below 50 and 200 copies/ml, respectively, at week 48. The primary endpoint was achieved in 105 (69.1%) control group patients versus 92 (63.4%) in the ABC/ddI (difference 5.6%, 95% confidence interval -5.1 to 16.4) and 97 (63.0%) in the DRV (difference 6.1%, 95% confidence interval -4.5 to 16.7) groups (non-inferiority not shown). Overall, less number of patients with baseline viral load at least 100 000 copies/ml (n = 122) had a viral load below 50 copies/ml at week 48 (37.7 versus 75.4%; P

Background A better understanding of why HIV-exposed/infected children fail to attend their scheduled follow-up medical appointments for HIV-related care would allow for interventions to enhance the delivery of care. The aim of this study was to determine characteristics of the caregiver-child dyad (CCD) associated with children’s non-adherence to scheduled follow-up medical appointments in HIV programs in Cameroon. Methods We conducted a case-control analysis of the usual-care group of CCDs from the MORE CARE trial, in which the effect of mobile phone reminders for HIV-exposed/infected children in attending follow-up appointments was assessed from January to March 2013. For this study, the absence of a child at their appointment was considered a case and the presence of a child at their appointment was defined as a control. We used three multivariate binary logistic regression analyses. The best-fit model was the one which had the smallest chi-square value with the Hosmer-Lemeshow test (HLχ²). Magnitudes of associations were expressed by odds ratio (OR), with a p-value

Summary Background Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine. Methods 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis. Findings At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per μL (IQR 78–167) and median plasma HIV-1 RNA was 104 736 copies per mL (40 804–243 787). The proportion of patients with undetectable viral load ( 10 copies per mL (–2·5 to –3·6) and in CD4 count 83 cells per μL (40–178). The probability of remaining alive or free of new AIDS-defining events was 0·85 (95% CI 0·73–0·92). Frequency of disease progression was 32·0 (95% CI 16·6–61·5), severe adverse effects 17·8 (7·4–42·7), and genotypic resistance mutations 7·1 (1·8–28·4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine. Interpretation Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.