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

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

Does smallpox vaccination modify HIV disease progression among ART-naive people living with HIV in Africa?

We examined the association between a history of smallpox vaccination and immune activation (IA) in a population of antiretroviral therapy-naïve people living with HIV (PLHIV). A cross-sectional study was conducted in Senegal from July 2015 to March 2017. Smallpox vaccination was ascertained by the presence of smallpox vaccine scar and IA by the plasma level of ß-2-microglobulin (ß2m). The association was analysed using logistic regression and linear regression models. The study population comprised 101 PLHIV born before 1980 with a median age of 47 years (interquartile range (IQR) = 42-55); 57·4% were women. Smallpox vaccine scar was present in 65·3% and the median ß2m level was 2·59 mg/l (IQR = 2·06-3·86). After adjustment, the presence of smallpox vaccine scar was not associated with a ß2m level ⩾2·59 mg/l (adjusted odds ratio 0·94; 95% confidence interval 0·32-2·77). This result was confirmed by the linear regression model. Our study does not find any association between the presence of smallpox vaccine scar and the ß2m level and does not support any association between a previous smallpox vaccination and HIV disease progression. In this study, IA is not a significant determinant of the reported non-targeted effect of smallpox vaccination in PLHIV.

Ethics of health research partnerships in Global South : PhD students in learning.

In view of the worldwide epidemic processes that require and result in simultaneous research in several countries and in an increasingly more structured scientific community, especially in countries of Global South, it is essential to establish partnerships between researchers, policy-makers, local supervisors, and communities in both the North and the South. The objectives of this essay are to: 1) present the context and issues linked to research in the framework of a North-South partnership; 2) describe the development of appropriate responses to improve consideration of ethical aspects; and 3) discuss the current role of young researchers in this era of multiple partnerships and share the observations and thoughts of PhD students in one research unit.

Prevalence of TB/HIV coinfection in antiretroviral-naïve patients at the Fann Ambulatory Treatment Center in Dakar.

To determine the prevalence of tuberculosis and describe its epidemiological, clinical, paraclinical, and therapeutic characteristics and its outcome in patients with HIV. This retrospective, descriptive, and analytical study examined the records of patients with HIV at our outpatient treatment center and selected those who were antiretroviral-naive and presented tuberculosis between January 2008 and December 2012. Among a total of 757 HIV-positive patients, 76 had tuberculosis, for a prevalence of 10 %. The sex ratio of 1.23 favored men. The average age was 42.5 years (range: 25 to 69 years. Nearly all these patients (71 cases) had HIV-1. A history of tuberculosis was reported by 39.5 %. Seventeen patients were malnourished. Management included chemoprophylaxis with cotrimoxazole for 64 patients. The pulmonary form predominated (72.4 %). Among these forms, there were 34 cases of negative microscopy tuberculosis and 21 cases of positive microscopy tuberculosis. The extrapulmonary forms (21 cases) were dominated by tuberculosis in the lymph nodes (11 cases), the pleura (7), pericardium (2), and peritoneum (1). Anemia was found in 44 patients. Severe immunosuppression was noted in 90 %, with CD4+ cell counts <350/mm3. Lethality was 7.9 %. TB/HIV coinfection is a major public health problem in Africa. Better coordination of activities in support of programs for tuberculosis and HIV/AIDS are needed.

Initial suboptimal CD4 reconstitution with antiretroviral therapy despite full viral suppression in a cohort of HIV-infected patients in Senegal.

OBJECTIVE: We determined the risk factors and incidence of clinical events associated with suboptimal immune reconstitution (SIR) defined by an increase in CD4 inferior to 50 cells/µL, from inclusion up to six months of antiretroviral treatment (ARVT), in patients with an undetectable viral load (<50 copies/mL). METHODS: Logistic regression and Cox's proportional hazards model were used to examine risk factors for SIR and the association between SIR and the risk of new clinical events or death, respectively after six months of ARVT. RESULTS: One hundred and two (15.5%) of the 657 patients presented with SIR. Age > 40 years (aOR = 1.74, 95% CI = 1.10-2.75), baseline CD4 ≥ 100 cells/µL (aOR = 2.06, 95% CI = 1.24-3.42), ARVT including AZT (aOR = 4.57, 95% CI=1.06-19.76), and the occurrence of a severe opportunistic infection during the first semester of ARVT (aOR = 2.38 95% CI= 1.49-3.80) were associated with SIR. After six months of ARVT and up to seven years of follow-up, 39 patients with SIR had presented with an opportunistic infection or death (rate= 9.78/100 person-years) compared to 168 with a normal recovery (rate = 7.75/100 person-years) but the difference was not statistically significant (aHR = 1.22, 95% CI = 0.85 to 1.74). CONCLUSION: SIR is less common in our country and is not associated with increased mortality or a greater incidence of opportunistic infections after six months of ARVT.

Tenofovir-emtricitabine-efavirenz in HIV-I-infected adults in Senegal: a 96-week pilot trial in treatment-naive patients.

We report the results of a pilot open-label trial of a tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) combination conducted in Dakar, Senegal. Forty HIV-1-infected patients, naive of antiretroviral treatment and without active opportunistic disease, were included and followed through 96 weeks. At weeks 48 and 96, respectively, 82.5% and 85% of patients had HIV-1 RNA <400 copies/mL (72.5% and 77.5% with HIV-1 RNA <50 copies/mL). Between baseline and week 96, the mean (SD) CD4 count increased from 126 (102) to 338 (155) cells/mm(3). The mean (SD) creatinine clearance decreased from 92 (36) to 73 (19) mL/min (P = .001). Treatment adherence was at least 94% at all scheduled visits. The efficacy and tolerability of a TDF/FTC/EFV combination were high and similar to those observed in Northern countries. This drug combination can be recommended in limited-resource countries, as did the World Health Organization (WHO) and should be made readily available as a fixed-dose combination.

Hepatitis B, C seroprevalence and delta viruses in HIV-1 Senegalese patients at HAART initiation (retrospective study).

The aim of this study was to determine hepatitis co-infection in a cohort of HIV infected patients at their inclusion in the Senegalese Initiative of ART Access. B, C, and D Hepatitis viruses serological markers were checked retrospectively on 363 stored plasma. For HBV, the Abbott laboratories equipment IMx was used to detect HBs Ag and anti Core Ab on negative HBs Ag samples. For HDV, anti Delta Ab was performed using the Abbott Murex Kit on all HBs Ag positive samples. For HCV, anti HCV Ab was detected by IMx as double screening test and confirmed by INNO-LIA(TM) HCV Core of Innogenetics laboratories. The statistical analysis was done with STATA V8. The study population was composed of 164 men and 199 women aged between 16 and 66 years. The immune and virological markers averages at their enrollment were 154 cell/mm(3) for TLCD4+ (n = 355 patients) and 4.9 log for viral load (n = 277 patients). HBs Ag was found in 61 patients or 16.8% and the prevalence of anti-HBc Ab was 83.2% (252/295). 2 patients or 3% on HBs Ag positive sample presents HBV/HDV co-infection Ab anti HCV was detects in 6 patients or 1.6% after confirmation and 2 patients had triple infection with HBV. These results showed that the prevalence of HBV and HCV in the population of persons living with HIV/AIDS in Senegal is similar to that found in the general population. Our data indicated that hepatitis pathology in the PLwHIV was essentially due to HBV. Further studies are needed to diagnose occult hepatitis in order to set up therapeutic strategies taking into account co-infections by hepatitis viruses in the ART programmes.

Quality of life and depression among HIV-infected patients receiving efavirenz- or protease inhibitor-based therapy in Senegal.

BACKGROUND: Efavirenz has been associated with neuropsychiatric disorders, but little is known about depression and quality of life in sub-Saharan Africa, where nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are still the first-line treatment recommended by the World Heath Organization (WHO) and are widely prescribed. METHODS: In a cross-sectional study, we evaluated quality of life and depression among Senegalese patients receiving efavirenz- or protease inhibitor (PI)-based regimens. Two hundred consecutive patients who had been taking highly active antiretroviral therapy (HAART) for more than 6 months were asked to complete a questionnaire. RESULTS: According to the Center for Epidemiologic Studies Depression Scale (CES-D), 18% had depression (19% for patients on a PI-based regimen and 17% for patients on efavirenz-based treatment). Fifty-nine per cent of the patients reported no health problems in the past 4 weeks. A quarter of patients had sleep disorders. Moderate or slight adverse events were reported by 28.5% of patients. CONCLUSIONS: Quality of life and depression scores remained good in both study groups. However, quality of life and depression should be monitored in follow-up of HIV-infected patients in sub-Saharan Africa.

[Peripheral neuropathies and antiretroviral drugs. Preliminary results]. / Neuropathies peripheriques et traitements antiretroviraux. Etude clinique, électrophysiologique et neuropathologique des biopsies neuro-musculaires chez 18 patients vih séropositifs. Résultats préliminaires.

INTRODUCTION: In order to appreciate the antiretroviral drugs impact in the HIV positive patients with peripheral neuropathy, a clinical, electrophysiological and neurpathological study of nerve biopsies was performed. PATIENTS AND METHODS: A group of 8 HIV seropositive patients with peripheral neuropathy was compared with an other group of 10 HIV seropositive patients treated with multiple antiretroviral drugs. Electrophysiological examination with motor nerve conduction velocity (MNCV) mesure of the median and the sciatic popliteal nerve was followed by nerve biopsy. Nerve fragments carried out the neuropathological technics for morphological examination. RESULTS: Eighteen seropositive HIV patients (16 HIV-1 and 2 HIV-2) were included in this study. Six patients among them had motor and sensitive neuropathy of the four limbs and 2 patients had sensitive neuropathy associated with pyramidal signs. In fine, 1 patient had sensitive neuropathy with distal amyotrophy of the four limbs. Slow MNCV was observed in all the patients and more severe in the lower limbs. Nerve were unexciting in the lower limbs in 2 patients. Nerve biopsy showed severe axonal loss in all the patients treated but one. They associated axonal lesion in 5 cases and myelinated lesions in 2 cases. Two patients non treated had normal nerve biopsy. Axonal loss was mild in 2 cases and very severe in one case associated with non inflammatory demyelinated lesions. CONCLUSION: we observed more severe and more frequent nerve lesions in treated patients than in no treated patients, as at the clinical, electrophysiological and neuropathological examination. Antiretroviral drugs cause more frequently pain motor and sensitive neuropathies at usual posologies. The occurence of recrudescence of pain peripheral neuropathy under antiretroviral treatment allows to reconsider drugs posologies.

[Efficacy and tolerance of non nucleosidic reverse transcriptase inhibitors containing tritherapy in HIV-1 infection]. / Efficacite et tolerance des tritherapies antiretrovirales comprenant un inhibiteur non nucleosidique de la transcriptase inverse du VIH-1.

INTRODUCTION: Antiretroviral therapy has dramatically changed the natural history of HIV infection. The aim of this study was to evaluate the effectiveness and tolerance of Non Nucleosidic Reverse Trancriptase Inhibitors containing regimens in HIV-1 infection. PATIENTS AND METHODS: This is a retrospective chart review of 257 HIV-1 infected patients followed in the infectious clinic ward of fann, from august 1998 to February 2002. RESULTS: Overall 195 patients (75.87%) were on efavirenz and 62 (25.2%) on nevirapine, with a male predominance (sex-ratio = 1.44). Baseline HIV-1 viral load was higher in efavirene group (p = 0.03). The two groups were comparable for immune restoration, tolerance, rate of treatment discontinuation and letality. The viral suppression was greater in efavirenz group at month 6 (p = 0.04). CONCLUSION: Non nucleosidic reverse transcriptase inhibitor containing regimens are effective and well tolerated. Those results make them suitable for first line therapy in HIV-1-infection.