Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model.

OBJECTIVES: Detailed simulation models are needed to assess strategies for prevention and treatment of hepatitis B virus (HBV) infection, the world's leading cause of liver disease. We sought to develop and validate a simulation model of chronic HBV that incorporates virological, serological and clinical outcomes. METHODS: We developed a novel Monte Carlo simulation model (the HEPA-B Model) detailing the natural history of chronic HBV. We parameterised the model with epidemiological data from the Western Pacific and sub-Saharan Africa. We simulated the evolution of HBV DNA, 'e' antigen (HBeAg) and surface antigen (HBsAg). We projected incidence of HBeAg loss, HBsAg loss, cirrhosis, hepatocellular carcinoma (HCC) and death over 10-year and lifetime horizons. We stratified outcomes by five HBV DNA categories at the time of HBeAg loss, ranging from HBV DNA<300 copies/mL to >106 copies/mL. We tested goodness of fit using intraclass coefficients (ICC). RESULTS: Model-projected incidence of HBeAg loss was 5.18% per year over lifetime (ICC, 0.969 (95% CI: 0.728 to 0.990)). For people in HBeAg-negative phases of infection, model-projected HBsAg loss ranged from 0.78% to 3.34% per year depending on HBV DNA level (ICC, 0.889 (95% CI: 0.542 to 0.959)). Model-projected incidence of cirrhosis was 0.29-2.09% per year (ICC, 0.965 (95% CI: 0.942 to 0.979)) and HCC incidence was 0.06-1.65% per year (ICC, 0.977 (95% CI: 0.962 to 0.986)). Over a lifetime simulation of HBV disease, mortality rates were higher for people with older age, higher HBV DNA level and liver-related complications, consistent with observational studies. CONCLUSIONS: We simulated HBV DNA-stratified clinical outcomes with the novel HEPA-B Model and validated them to observational data. This model can be used to examine strategies of HBV prevention and management.

Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) epidemic has spread from China to 25 countries. Local cycles of transmission have already occurred in 12 countries after case importation. In Africa, Egypt has so far confirmed one case. The management and control of COVID-19 importations heavily rely on a country's health capacity. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of COVID-19. METHODS: We used data on the volume of air travel departing from airports in the infected provinces in China and directed to Africa to estimate the risk of importation per country. We determined the country's capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulations Monitoring and Evaluation Framework; and vulnerability, using the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing most to their risk. FINDINGS: Countries with the highest importation risk (ie, Egypt, Algeria, and South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (ie, Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, and Kenya) have variable capacity and high vulnerability. We identified three clusters of countries that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and the city of Beijing, respectively. INTERPRETATION: Many countries in Africa are stepping up their preparedness to detect and cope with COVID-19 importations. Resources, intensified surveillance, and capacity building should be urgently prioritised in countries with moderate risk that might be ill-prepared to detect imported cases and to limit onward transmission. FUNDING: EU Framework Programme for Research and Innovation Horizon 2020, Agence Nationale de la Recherche.

HIV self-testing: The key to unlock the first 90 in West and Central Africa.

The West and Central African region (WCAR) still registers some of the highest rates of new HIV infections worldwide (16%) despite a low prevalence of HIV (1.9%). In this region, only 48% of people living with HIV are aware of their HIV status. To fill this gap, HIV Self testing (HIVST) could potentially be an additional approach to overcome the barriers to diagnose HIV infected patients, therefore being one of the keys to unlock the first 90 as recommended by the World Health Organization (WHO) since 2016. However, many challenges remain for the adoption of HIVST in routine clinical practice in low prevalence settings and need to be contextualized to WCAR settings. We report in this paper some of the challenges and discuss opportunities for a successful implementation of HIVST in the WCAR.

Sexual health needs of female sex workers in Côte d'Ivoire: a mixed-methods study to prepare the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention.

OBJECTIVE: To describe sexual and reproductive health (SRH) needs of female sex workers (FSWs) to inform the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention in this population. DESIGN AND SETTING: The ANRS 12361 PrEP-CI cross-sectional and mixed-methods study was designed and implemented with two community-based organisations in Côte d'Ivoire. PARTICIPANTS: A convenience sample of 1000 FSWs aged ≥18, not known as HIV-positive, completed a standardised questionnaire assessing sociodemographic characteristics, sexual practices, use of community health services and a priori acceptability of PrEP. Twenty-two indepth interviews and eight focus group discussions were also conducted to document FSWs' risky practices and sexual behaviours, experiences with violence and discrimination, attitudes regarding HIV and sexually transmitted infections (STIs), and barriers to SRH services. RESULTS: Although 87% described consistent condom use with clients, more than 22% declared accepting condomless sexual intercourse for a large sum of money. Furthermore, condom use with their steady partner and knowledge of their partner's HIV status were low despite their acknowledged concurrent sexual partnerships. While inconsistent condom use exposed FSWs to STIs and undesired pregnancies, the prevalence of contraceptive strategies other than condoms was low (39%) due to fear of contraception causing sterility. FSWs faced obstacles to accessing SRH care and preferred advice from their peers or self-medication. CONCLUSIONS: Despite adoption of preventive behaviour in most cases, FSWs are still highly exposed to HIV. Furthermore, FSWs seem to face several barriers to accessing SRH. Implementing PrEP among FSWs in West Africa, such as in Côte d'Ivoire, constitutes an opportunity to consider the regular follow-up of HIV-negative FSWs. PrEP initiation should not condition access to SRH services; conversely, SRH services could be a way to attract FSWs into HIV prevention. Our results highlight the importance of developing a people-focused approach that integrates all SRH needs when transitioning from PrEP efficacy trials to implementation.

Hepatitis B virus activity in untreated hepatitis B e antigen-negative human immunodeficiency virus-hepatitis B virus co-infected patients from sub-Saharan Africa.

BACKGROUND: In human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients from sub-Saharan Africa with hepatitis B e antigen (HBeAg)-negative status, data are limited on the evolution of HBV activity when antiretroviral treatment (ART) is absent. METHODS: A total of 43 HBeAg-negative co-infected patients not indicated for ART (per concomitant World Health Organization recommendations) were followed during participation in a randomized controlled trial in Côte d'Ivoire. Chronic HBeAg-negative phases were classified at yearly visits and defined as 'infection' (HBV DNA ≤10 000 copies/mL and normal alanine aminotransferase [ALT]) or 'hepatitis' (HBV DNA >10 000 copies/mL and/or above normal ALT). Dispersion in HBV DNA and ALT levels during follow-up was assessed using interquartile range (IQR) regression. RESULTS: During a median 25 months (IQR 19-31), 17 (40%) patients consistently had 'infection', 5 (12%) consistently had 'hepatitis' and 21 (48%) fluctuated between phases. Wider dispersion in HBV DNA over time was associated with higher baseline HIV RNA (p=0.02) and higher baseline HBV DNA levels (p=0.008), while wider dispersion in ALT was associated with higher baseline HIV RNA (p<0.001), higher baseline ALT levels (p=0.02) and baseline hepatitis surface antigen >4.0 log10 IU/mL (p=0.02). CONCLUSIONS: HBV activity is common with HBeAg-negative status, whose variation is partly linked to HIV replication. Fluctuations in disease phase make it difficult to assess the risk of morbidity and mortality after ART initiation.

Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa.

BACKGROUND & AIMS: Replication markers exhibit substantial variation during chronic hepatitis B virus (HBV) infection, part of which can be explained by mutations on the surface (S) gene. We aimed to identify S-gene mutations possibly influencing the quantification of HBV replication markers (MUPIQH) in HBV genotype E infection, common to Western Africa. METHODS: Seventy-three antiretroviral treatment (ART)-naïve human immunodeficiency virus (HIV)-HBV co-infected patients from Côte d'Ivoire, initiating anti-HBV-containing ART, had available HBV S-gene sequences. S-gene MUPIQHs were screened at ART initiation based on lower HBV-DNA or HBsAg quantification (qHBsAg) compared to wildtype. Their association with HBV virological response and qHBsAg slope during treatment was evaluated. RESULTS: Genotype E was predominant (95.9%). At ART initiation, median HBV-DNA was 7.27 log10 copies/mL (IQR = 5.26-8.33) and qHBsAg 4.08 log10 IU/mL (IQR = 3.49-4.61). Twelve S-gene MUPIQHs were identified among 21 patients (28.8%): sS140L (n = 4), sD144A (n = 1), sS167L (n = 2), sS174N (n = 6), sP178Q (n = 2), sG185L (n = 2), sW191L (n = 2), sP203Q/R (n = 2), sS204N/I/R/K/T/G (n = 7), sN207T (n = 2), sF212C (n = 1) and sV224A/Y (n = 7). MUPIQHs at positions s185+s191+s224 and s178+s204 were within highly covarying networks of S-gene mutations. Older age (P = 0.02), elevated transaminases (P = 0.03) and anti-hepatitis B "e" antibody-positive serology (P = 0.009) were significantly associated with prevalent MUPIQHs at ART initiation. During treatment, baseline MUPIQHs were not associated with time-to-undetectable HBV-DNA (P = 0.7) and qHBsAg levels decreased at similar rates between those with vs without MUPIQHs (P = 0.5). CONCLUSION: Several novel S-gene mutations were associated with reductions in replication markers among West African co-infected patients. These mutations, however, do not affect response during antiviral treatment. Their diagnostic and clinical consequences need clarification.

Aging with HIV: what effect on mortality and loss to follow-up in the course of antiretroviral therapy? The IeDEA West Africa Cohort Collaboration.

BACKGROUND: Reporting mortality and lost to follow-up (LTFU) by age is essential as older HIV-positive patients might be at risk of long-term effects of living with HIV and/or taking antiretroviral therapy (ART). As age effects might not be linear and might impact HIV outcomes in the oldest more severely, people living with HIV (PLHIV) aged 50-59 years and PLHIV aged >60 years were considered separately. SETTING: Seventeen adult HIV/AIDS clinics spread over nine countries in West Africa. METHODS: Data were collected within the International Epidemiological Databases to Evaluate AIDS West Africa Collaboration. ART-naïve PLHIV-1 adults aged >16 years initiating ART and attending ≥2 clinic visits were included (N=73,525). Age was divided into five groups: 16-29/30-39/40-49/50-59/≥60 years. The age effect on mortality and LTFU was evaluated with Kaplan-Meier curves and multivariable Cox proportional hazard regressions. RESULTS: At month 36, 5.9% of the patients had died and 47.3% were LTFU. Patients aged ≥60 (N=1,736) and between 50-59 years old (N=6,792) had an increased risk of death in the first 36 months on ART (adjusted hazard ratio=1.66; 95% CI: 1.36-2.03 and adjusted hazard ratio=1.31; 95% CI: 1.15-1.49, respectively; reference: <30 years old). Patients ≥60 years old tend to be more often LTFU. CONCLUSION: The oldest PLHIV presented the poorest outcomes, suggesting that the PLHIV aged >50 years old should not be considered as a unique group irrespective of their age. Tailored programs focusing on improving the care services for older PLHIV in Sub-Saharan Africa are clearly needed to improve basic program outcomes.

CD4+ T Cell Recovery and Hepatitis B Virus Coinfection in HIV-Infected Patients from Côte d'Ivoire Initiating Antiretroviral Therapy.

Immunorecovery could be attenuated in HIV-hepatitis B virus (HBV) coinfection versus HIV monoinfection during antiretroviral therapy (ART), yet, whether it also occurs in individuals from sub-Saharan Africa without severe comorbidities is unknown. In this study, 808 HIV-infected patients in Côte d'Ivoire initiating continuous ART were included. Six-month CD4+ count trajectories and the proportion reaching CD4+ T cell counts >350/mm3, HIV-RNA <300 copies/mL, still alive and not lost to follow-up within 18 months ("optimal immunorecovery") were compared between coinfected groups. At inclusion, 80 (9.9%) patients were HIV-HBV coinfected, 40 (50.0%) of whom had high HBV-DNA viral load (VL) (>104 copies/mL). Coinfected patients with high HBV-DNA replication initiated ART with significantly lower median CD4+ T cell counts [216/mm3, interquartile range (IQR) = 150-286] compared to coinfection with low HBV-DNA replication (268/mm3, IQR = 178-375) or HIV monoinfection (257/mm3, IQR = 194-329) (p = .003). These patients had significantly faster rates of CD4+ cell count increase from baseline after adjusting for baseline age, World Health Organization stage III/IV, and CD4+ cell counts (p = .04), yet, were not more likely to exhibit optimal immunorecovery (82.5% vs. 80.0% and 77.9%, respectively) (p = .8). In conclusion, change in CD4+ cell counts after ART-initiation was accelerated in coinfected patients with high HBV DNA VLs, but this did not lead to increased rates of optimal immunorecovery.

[Thromboembolic manifestations in 36 HIV-infected patients in West Africa]. / Manifestations thromboemboliques chez 36 patients Ouest Africains infectés par le VIH.

In HIV-infected patients thromboembolic disease is a complication linked to heightened risk. In Ivory Coast no study has been conducted on HIV-infected patients treated in HIV Services. The aim of our study is to describe HIV-associated thromboembolic manifestations in patients treated or untreated with antiretroviral drugs whose data were collected in the Infectious and Tropical Diseases Service (ITDS). We conducted a retrospective study by reviewing the medical records of HIV-infected patients hospitalized with deep vein thrombosis (DVT), arterial thrombosis and/or pulmonary embolism over the period January 2005-July 2015. Diagnosis was based on Doppler ultrasound of vessels and/or on thoracic angioscanner. Diagnostic, therapeutic and evolutionary features of thromboembolic manifestations in these patients were analyzed. The medical records of 36 patients, including 23 women (64%), with a sex-ratio M/F of 0.57 and an average age of 43±12 years were selected. Deep venous thrombosis (DVT) was found in 26 (72.2%) patients, pulmonary embolism (PE) in 9 (25%) patients and arterial thrombosis in 1 patient (2.8%). DVT was unilateral in 81% of cases and predominantly left-sided in 77% of cases. PE was unilateral and right-sided in 100% of cases while arterial thrombosis was bilateral in 2.7% of cases. In patients with DVT, the femoral vein (39%) and the popliteal vein (35%) were most commonly affected by thrombosis. PE involved the pulmonary arteries in 77.8% of cases while arterial thrombosis involved the left and right internal carotid. The majority of patients was under antiretroviral treatment (69%). The most commonly associated opportunistic infections included oral candidiasis (31%) and tuberculosis (33%). Nine patients died (25%). This study highlights high rates of DVT in HIV-infected patients. Other studies are necessary to better understand the role of HIV in the occurrence of thromboembolic disease.

[Aortic aneurism dissection in an adult patient with tuberculosis infected with HIV-1 during immune reconstitution inflammatory syndrome]. / Dissection aortique anévrismale chez un adulte infecté par le VIH-1 dans le cadre d'un syndrome de reconstitution immune avec tuberculose.

We here report the case of a 35-year old man with HIV-1 but with no previous medical-surgical history hospitalized in Abidjan, Côte d'Ivoire, due to fever, cough, dyspnea, chest pain and unfolding of the aortic arch observed on chest x-ray a week after having started antiretroviral therapy (ART). CT angiography of the thoracic aorta showed overall, extended aortic ectasia with mural thrombus. Transesophageal echocardiography objectified type A ascending aortic dissection (Stanford classification). The diagnosis of tuberculosis was confirmed based on Mycobacterium tuberculosis culture isolation. Eight years after, the patient was still alive without surgical treatment and complained of intermittent chest pain. Blood pressure was stable with moderate renal failure. We here report a rare case of aortic aneurism dissection in an adult patient with tuberculosis infected with HIV-1 during immune reconstitution inflammatory syndrome.

Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.

Background: In human immunodeficiency virus (HIV)-infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults. Methods: The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIV-infected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression. Results: A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/µL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26-5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36-2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality. Conclusions: African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population. Clinical Trials Registration: NCT00495651.

Clinical Outcomes during Treatment Interruptions in Human Immunodeficiency Virus-Hepatitis B Virus Co-infected Patients from Sub-Saharan Africa.

Antiretroviral treatment (ART) interruptions increase the risk of severe morbidity/mortality in human immunodeficiency virus (HIV)-infected individuals from subSaharan Africa. We aimed to determine whether the risk is further increased among HIV-hepatitis B virus (HBV) co-infected patients in this setting. In this sub-analysis of a randomized-control trial, 632 participants from Côte d'Ivoire randomized to receive continuous-ART (C-ART), structured ART interruptions of 2-months off, 4-months on (2/4-ART), and CD4-guided ART interruptions (CD4GT, interruption at 350/mm3 and reintroduction at 250/mm3) were analyzed. Incidence rates (IR) of serious HIV- and non-HIV-related morbidity were compared between patients stratified on hepatitis B surface antigen (HBsAg) status. Overall, 65 (10.3%) were HBsAg-positive, 29 (44.6%) of whom had HBV-DNA levels > 10,000 copies/mL. After a median 2.0 year (range = 0.2-3.1) follow-up, ≥ 1 serious HIV-related events occurred in 101 HIV mono-infected and 15 HIV-HBV co-infected patients (IR = 10.0 versus 13.2/100 person/years, respectively, P = 0.3), whereas the highest incidence was observed in co-infected patients with baseline HBV-replication > 10,000 copies/mL (IR = 24.0/100 person/years, P versus HIV mono-infected = 0.002). Incidence of bacterial infections was also highest in the co-infected group with HBV-replication > 10,000 copies/mL (IR = 12.9 versus 3.3/100 person/years in HIV mono-infected patients, P = 0.001). The relative effect of CD4GT or 2/4-ART versus C-ART was not different between infection groups (P for interaction = 0.4). No increase in the incidence of non-HIV-related morbidity was observed for co-infected patients (P = 0.5), even at HBV-replication levels > 10,000 copies/mL (P = 0.7). In conclusion, co-infected patients with elevated HBV-replication at ART-initiation are more susceptible to HIV-related morbidity, especially invasive bacterial diseases, during treatment interruption.

High correlation between Framingham equations with BMI and with lipids to estimate cardiovascular risks score at baseline in HIV-infected adults in the Temprano trial, ANRS 12136 in Côte d'Ivoire.

CONTEXT: Data on cardiovascular risk (CVR) score among HIV-infected patients in sub-Saharan Africa are scarce. Our first objective was to compare the CVR score of Framingham utilizing BMI and lipids at baseline, and secondary to assess evolution of CVR score over time at Month 30 in the Temprano trial. METHODS: HIV-infected adults with CD4 <800/mm3 without criteria for initiating ART were included and followed for 30 months in the Temprano trial, which assessed the benefits and risks of early antiretroviral treatment (ART) vs deferred ART. CVR score was estimated at baseline and Month-30 using Framingham equations with either BMI or lipids and classified as high (>20%), moderate (10-20%), and low risk (<10%). At baseline, we compare these two estimations utilizing the Pearson correlation test and analyze the increasing CV risk score over time by Proportional odds cumulative logit models for people attending the Month-30 (M30) visit. RESULTS: Among the 2056 patients, 78% were women, median age was 35 years, and median CD4 count was 464/mm3, 6.8% were obese, 6.3% had hypertension, 7.8% were smokers (1.8% women, 26.8% men), 19% had Total Cholesterol (TC) >5mmol/L, and 1% diabetes at baseline. At baseline the concordance between the two Framingham equations was excellent (r = 0.95; p<0.0001). Among the 1700 patients who attended M30 visit and with available data, 1.3% had a high CV risk score at baseline and 3.1% at M30 visit using Framingham equation with BMI. Adjusted odds ratio (aOR) of being at a higher CV risk score at M30 visit compared to a higher CV risk score at M0 visit was 1.35 (CI 95% 1.17-1.57). Stratified by sex, the increasing CV risk score was OR 1.73 (CI 95%: 1.30-2.29) for women and OR 1.24 (CI 95%: 1.02-1.50) for men. Early ART was not associated with an increasing CV risk score (p = 0.88). Results for the 1422 patients with Framingham equation using lipids were similar. CONCLUSION: In a large trial evaluating early ART for HIV infection in Côte d'Ivoire, Framingham equation with BMI and lipids were highly correlated and CV risk score increases over time. Early ART was not significantly associated with this increasing CV risk score.

Ending AIDS as a public health threat by 2030: Scientific Developments from the 2016 INTEREST Conference in Yaoundé, Cameroon.

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.

Immunologic response in treatment-naïve HIV-2-infected patients: the IeDEA West Africa cohort.

INTRODUCTION: Response to antiretroviral therapy (ART) among individuals infected with HIV-2 is poorly described. We compared the immunological response among patients treated with three nucleoside reverse-transcriptase inhibitors (NRTIs) to boosted protease inhibitor (PI) and unboosted PI-based regimens in West Africa. METHODS: This prospective cohort study enrolled treatment-naïve HIV-2-infected patients within the International Epidemiological Databases to Evaluate AIDS collaboration in West Africa. We used mixed models to compare the CD4 count response to treatment over 12 months between regimens. RESULTS: Of 422 HIV-2-infected patients, 285 (67.5%) were treated with a boosted PI-based regimen, 104 (24.6%) with an unboosted PI-based regimen and 33 (7.8%) with three NRTIs. Treatment groups were comparable with regard to gender (54.5% female) and median age at ART initiation (45.3 years; interquartile range 38.3 to 51.8). Treatment groups differed by clinical stage (21.2%, 16.8% and 17.3% at CDC Stage C or World Health Organization Stage IV for the triple NRTI, boosted PI and unboosted PI groups, respectively, p=0.02), median length of follow-up (12.9, 17.7 and 44.0 months for the triple NRTI, the boosted PI and the unboosted PI groups, respectively, p<0.001) and baseline median CD4 count (192, 173 and 129 cells/µl in the triple NRTI, the boosted PI and the unboosted PI-based regimen groups, respectively, p=0.003). CD4 count recovery at 12 months was higher for patients treated with boosted PI-based regimens than those treated with three NRTIs or with unboosted PI-based regimens (191 cells/µl, 95% CI 142 to 241; 110 cells/µl, 95% CI 29 to 192; 133 cells/µl, 95% CI 80 to 186, respectively, p=0.004). CONCLUSIONS: In this observational study using African data, boosted PI-containing regimens had better immunological response compared to triple NRTI combinations and unboosted PI-based regimens at 12 months. A randomized clinical trial is still required to determine the best initial regimen for treating HIV-2 infected patients.

Hepatitis B surface antigen quantification as a predictor of seroclearance during treatment in HIV-hepatitis B virus coinfected patients from Sub-Saharan Africa.

BACKGROUND AND AIM: In Sub-Saharan Africa, seroclearance of hepatitis B surface antigen (HBsAg) and hepatitis B "e" antigen (HBeAg), including their quantifiable markers, have rarely been evaluated during long-term antiviral treatment among patients coinfected with HIV and hepatitis B virus (HBV). METHODS: In this prospective cohort study from two randomized-control trials in Côte d'Ivoire, 161 antiretroviral-naïve HIV-HBV coinfected patients starting lamivudine (n = 76) or tenofovir/emtricitabine (n = 85) containing antiretroviral therapy were included. HBV DNA was quantified using an in-house assay (detection limit = 12 copies/mL) and HBsAg quantification (qHBsAg) using the Elecsys assay. RESULTS: Overall, 33 (20.5%) patients were HBeAg positive, 121 (75.2%) had detectable HBV DNA, and 92/93 (98.9%) harbored HBV genotype E. Median treatment duration was 35.5 months (interquartile range: 24.3-36.4). Among HBeAg-positive patients, cumulative proportion with HBeAg seroclearance was 46.3% (n = 14). Overall, cumulative proportion of HBsAg seroclearance was 6.6% (n = 10). Lower baseline qHBsAg levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance for both HBeAg-negative and HBeAg-positive patients. When taken at certain levels, these determinants provided moderate sensitivity (Se) and specificity (Sp) in predicting HBsAg seroclearance at month 36 (≤ 1000 IU/mL at baseline, Se = 0.80, Sp = 0.80; ≥ 1.0 log10 IU/mL drop at month 12, Se = 0.57, Sp = 1.00). Instead, qHBsAg levels ≤ 100 or ≤ 10 IU/mL at month 12 were optimal (both Se = 0.90 and Sp = 1.00). Detectable HBV-DNA provided fairly high Se and Sp when evaluated at baseline (Se = 1.00, Sp = 0.80), but not at month 12 (Se = 0.80, Sp = 0.40). CONCLUSIONS: HBsAg seroclearance rates are not common in patients from Sub-Saharan Africa treated with anti-HBV containing antiretroviral therapy. qHBsAg levels at 12 months of treatment may accurately predict HBsAg seroclearance.

Identifying patients infected with hepatitis B virus in sub-Saharan Africa: potential for misclassification.

Most research in sub-Saharan Africa establishes hepatitis B infection via one-time hepatitis B surface antigen (HBsAg) testing. Of 237 HIV-infected patients from two clinical trials testing HBsAg positive (MiniVidas®), 206 (86.9%) had validated serological tests using another assay (Architect). Discrepancies could be due to inactive infection, highlighting the importance of assessing hepatitis B virus infection phase.

Metabolic disorders and cardiovascular risk in treatment-naive HIV-infected patients of sub-saharan origin starting antiretrovirals: impact of westernized lifestyle.

In a cohort of HIV-infected patients of sub-Saharan origin we describe the incidence of metabolic syndrome, insulin resistance, and lipodystrophy after 3 years of combined antiretroviral therapy, and model the 10-year risk of cardiovascular diseases, while taking into account environmental factors. This is a multinational, prospective cohort study conducted in HIV outpatient clinics from four tertiary care centers set in France and Côte d'Ivoire. The participants were HIV-infected, treatment-naive patients eligible to start antiretroviral treatment and were of sub-Saharan African origin. The main outcome measures were the incidence of metabolic syndrome, insulin resistance, and lipodystrophy, and the assessment of the 10-year risk of cardiovascular diseases using Framingham risk prediction, D.A.D. Cardiovascular Disease Risk, and WHO/ISH prediction charts. Of 245 patients followed for up to 3 years, the incidence of metabolic syndrome, insulin resistance, and lipodystrophy was 5.5, 8.5, and 6.8 per 100 person-years of follow-up (cumulative incidence: 14.4%, 19.2%, and 18.1%, respectively). Living in France as well as female gender and being overweight were risk factors for metabolic disorders as whole and only first generation protease inhibitors were marginally associated with metabolic syndrome. Cardiovascular risk as modeled through the three equations was high in all patients with the synergistic and deleterious effect of living in France compared to Côte d'Ivoire. This cohort study shows how the synergy between HIV, antiretroviral (ARV) exposure, and westernization of life style in a cohort of HIV-infected patients of sub-Saharan origin leads to a progressive increase in the risk of lipodystrophy, as well as metabolic syndrome and insulin resistance, all associated with increased cardiovascular risk.

How to optimize hepatitis C virus treatment impact on life years saved in resource-constrained countries.

UNLABELLED: In resource-constrained countries where the prevalence of hepatitis C virus (HCV) disease is usually high, it is important to know which population should be treated first in order to increase treatment effectiveness. The aim was to estimate the effectiveness of different HCV treatment eligibility scenarios in three different countries. Using a Markov model, we estimated the number of life-years saved (LYS) with different treatment eligibility scenarios according to fibrosis stage (F1-F4 or F3-4), compared to base case (F2-F4), at a constant treatment rate, of patients between 18 and 60 years of age, at stages F0/F1 to F4, without liver complications or coinfections, chronically infected by HCV, and treated with pegylated interferon (IFN)/ribavirin or more-efficacious therapies (i.e. IFN free). We conducted the analysis in Egypt (prevalence = 14.7%; 45,000 patients treated/year), Thailand (prevalence = 2.2%; 1,000 patients treated/year), and Côte d'Ivoire (prevalence = 3%; 150 patients treated/year). In Egypt, treating F1 patients in addition to ≥F2 patients (SE1 vs. SE0) decreased LYS by 3.9%. Focusing treatment only on F3-F4 patients increased LYS by 6.7% (SE2 vs. SE0). In Thailand and Côte d'Ivoire, focusing treatment only on F3-F4 patients increased LYS by 15.3% and 11.0%, respectively, compared to treating patients ≥F2 (ST0 and SC0, respectively). Treatment only for patients at stages F3-F4 with IFN-free therapies would increase LYS by 16.7% versus SE0 in Egypt, 22.0% versus ST0 in Thailand, and 13.1% versus SC0 in Côte d'Ivoire. In this study, we did not take into account the yearly new infections and the impact of treatment on HCV transmission. CONCLUSION: Our model-based analysis demonstrates that prioritizing treatment in F3-F4 patients in resource-constrained countries is the most effective scenario in terms of LYS, regardless of treatment considered.