Efficacy and safety of three antiretroviral therapy regimens for treatment-naive African adults living with HIV-2 (FIT-2): a pilot, phase 2, non-comparative, open-label, randomised controlled trial.

BACKGROUND: Due to the low number of individuals with HIV-2, no randomised trials of HIV-2 treatment have ever been done. We hypothesised that a non-comparative study describing the outcomes of several antiretroviral therapy (ART) regimens in parallel groups would improve understanding of how differences between HIV-1 and HIV-2 might lead to different therapeutic approaches. METHODS: This pilot, phase 2, non-comparative, open-label, randomised controlled trial was done in Burkina Faso, Côte d'Ivoire, Senegal, and Togo. Adults with HIV-2 who were ART naive with CD4 counts of 200 cells per µL or greater were randomly assigned 1:1:1 to one of three treatment groups. A computer-generated sequentially numbered block randomisation list stratified by country was used for online allocation to the next available treatment group. In all groups, tenofovir disoproxil fumarate (henceforth tenofovir) was dosed at 245 mg once daily with either emtricitabine at 200 mg once daily or lamivudine at 300 mg once daily. The triple nucleoside reverse transcriptase inhibitor (NRTI) group received zidovudine at 250 mg twice daily. The ritonavir-boosted lopinavir group received lopinavir at 400 mg twice daily boosted with ritonavir at 100 mg twice daily. The raltegravir group received raltegravir at 400 mg twice daily. The primary outcome was the rate of treatment success at week 96, defined as an absence of serious morbidity event during follow-up, plasma HIV-2 RNA less than 50 copies per mL at week 96, and a substantial increase in CD4 cells between baseline and week 96. This trial is registered at ClinicalTrials.gov, NCT02150993, and is closed to new participants. FINDINGS: Between Jan 26, 2016, and June 29, 2017, 210 participants were randomly assigned to treatment groups. Five participants died during the 96 weeks of follow-up (triple NRTI group, n=2; ritonavir-boosted lopinavir group, n=2; and raltegravir group, n=1), eight had a serious morbidity event (triple NRTI group, n=4; ritonavir-boosted lopinavir group, n=3; and raltegravir group, n=1), 17 had plasma HIV-2 RNA of 50 copies per mL or greater at least once (triple NRTI group, n=11; ritonavir-boosted lopinavir group, n=4; and raltegravir group, n=2), 32 (all in the triple NRTI group) switched to another ART regimen, and 18 permanently discontinued ART (triple NRTI group, n=5; ritonavir-boosted lopinavir group, n=7; and raltegravir group, n=6). The Data Safety Monitoring Board recommended premature termination of the triple NRTI regimen for safety reasons. The overall treatment success rate was 57% (95% CI 47-66) in the ritonavir-boosted lopinavir group and 59% (49-68) in the raltegravir group. INTERPRETATION: The raltegravir and ritonavir-boosted lopinavir regimens were efficient and safe in adults with HIV-2. Both regimens could be compared in future phase 3 trials. The results of this pilot study suggest a trend towards better virological and immunological efficacy in the raltegravir-based regimen. FUNDING: ANRS MIE.

Implementation of an intensive adherence intervention in patients with second-line antiretroviral therapy failure in four west African countries with little access to genotypic resistance testing: a prospective cohort study.

BACKGROUND: The decision about whether to switch to third-line antiretroviral therapy (ART) in patients with treatment failure on second-line therapy is difficult in settings with little access to genotypic resistance testing. In this study, we used a standardised algorithm including a wide range of adherence-enhancing interventions followed by a new viral load measurement to decide whether to switch to third-line therapy in this situation. The decision, made on the basis of effectiveness of the adherence reinforcement to drive viral resuppression, did not use genotypic resistance testing. METHODS: In this prospective cohort study, adults in four west African countries with treatment failure of a boosted protease inhibitor ART regimen were offered nine adherence reinforcement interventions, and followed up for 64 weeks. We measured viral load at week 12 and used the results to decide ART treatment at week 16: if successful resuppression (plasma HIV-1 RNA <400 copies per mL or had decreased by ≥2 log10 copies per mL compared with baseline), patients continued the same second-line regimen; otherwise they switched to a third-line regimen based on ritonavir-boosted darunavir and raltegravir. The primary endpoint was virological success at week 64 (plasma HIV-1 RNA <50 copies per mL). After study termination we did genotypic resistance testing on frozen plasma samples collected at baseline, and retrospectively determined the appropriateness of the week 16 decision on the basis of the baseline genotypic susceptibility score. FINDINGS: Between March 28, 2013, and May 11, 2015, of the 198 eligible participants, five died before week 16. Of the 193 remaining, 130 (67%) reached viral resuppression and continued with second-line ART, and 63 (33%) switched to third-line ART at week 16. Post-study genotypic resistance testing showed that the baseline genotypic susceptibility score was calculable in 166 patients, of whom 57 (34%) had a score less than 2. We retrospectively concluded that the week 16 decision was appropriate in 145 (75%) patients. At week 64, four patients (2%) were lost to follow-up, ten (5%) had died, and 101 (52%) had a viral load less than 50 copies per mL. INTERPRETATION: Poor adherence is the first problem to tackle in patients for whom second-line ART is failing when resistance tests are not routinely available and is effectively a manageable problem. Lack of access to genotypic resistance testing should not be an obstacle to the prescription of third-line ART in patients who do not achieve viral resuppression after adherence reinforcement. FUNDING: French Agency for Research on AIDS and Viral Hepatitis.

Secret intake of antiretroviral treatment and HIV-1 viremia in a public routine clinic in Burkina Faso: a surprising relationship.

In sub-Saharan Africa, where people living with HIV are frequently stigmatized, the intake of antiretroviral treatment (ART) remains a critical issue for many patients. Although the secret intake of ART may hinder the adherence to treatment, data on its specific impact on therapeutic effectiveness are lacking. We therefore assessed the association between secret intake of ART (i.e., hidden from family) and HIV-1 viremia among patients treated in a public routine clinic in Burkina Faso. We performed a cross-sectional study from December 2012 to September 2013 among patients on ART at the Day Care Unit in Bobo Dioulasso. Patients were eligible for the study if they were 15 years old or over, infected with HIV-1 or HIV-1 + 2, and on ART for at least six months. HIV-1 viral load was measured using Biocentric or Abbott Real Time assay. Study-specific data were collected by social workers using face-to-face interviews, and medical data using the routine electronic database. The association between secret intake of ART and viral load >300 copies/mL was assessed using a multivariate logistic regression. Of 771 patients (women 81.4%; median age 41 years; median time on ART 51 months), 408 reported secret intake of ART and 363 declared open intake. Compared to the latter, patients who hid their intake were younger, more likely to be women and to be involved in a polygamist or in a non-cohabiting union. Viremia was observed in 4.4% of patients hiding ART intake and 9.4% of those taking it openly. By multivariate analysis, secret intake of ART was significantly associated with a lower risk of viremia (adjusted odds ratio 0.41, 95% confidence interval 0.22-0.76). The unexpected relation between secret intake of ART and viremia found in this study requires further investigations. Quantitative and qualitative studies need to be performed.

Short Communication: Nucleoside Reverse Transcriptase Inhibitors with Reduced Predicted Activity Do Not Impair Second-Line Therapy with Lopinavir/Ritonavir or Darunavir/Ritonavir.

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] <50 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] <1), intermediate (GSS = 1), and high predicted NRTI activity (GSS >1) 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 > .05). High VL at switch was the only consistent prognostic factor for VF after multivariate adjustment (p < .01). Suboptimal adherence, high predicted RTI activity, or low NRTI mutations were associated with VF (p < .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.

Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa.

BACKGROUND: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. METHODS: A medical chart review was conducted in large urban HIV treatment centers in Côte d'Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. RESULTS: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4-14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02-4.79) had a confirmed HCV infection. CONCLUSIONS: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012.

TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

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-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/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/µl (IQR: 113-319 cells/µl). 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 (ß = -10.8 [-18.1,-3.5] for women), age (ß = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (ß = +0.8 [0.1,1.5] per unit of BMI), and study site (ß = +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.

Prevalence of hepatitis B and delta according to HIV-type: a multi-country cross-sectional survey in West Africa.

BACKGROUND: In West Africa where HIV-1 and HIV-2 co-circulate, the co-infection with hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is not well described. This study aimed at estimating the prevalence of HBV and HBV/HDV co-infection according to HIV types and risk factors for HBV infection among West African HIV-infected patients. METHOD: A cross-sectional survey was conducted within the IeDEA West Africa cohort from March to December 2012 in Côte d'Ivoire (three sites), Burkina Faso and Mali (one site each). All HIV-infected adult patients on antiretroviral therapy (ART) or not who attended one of the participating HIV clinics during the study period and agreed to participate were included. Blood samples were collected and re-tested for HIV type discrimination, HBV and HDV serology as well as HBV viral load. Logistic regression was used to identify risk factors for HBV infection. RESULTS: A total of 791 patients were included: 192 HIV-1, 447 HIV-2 and 152 HIV-1&2 dually reactive. At time of sampling, 555 (70.2%) were on ART and median CD4+ cell count was 472/mm3 (inter-quartile range [IQR]: IQR: 294-644). Sixty-seven (8.5%, 95% CI 6.6-10.6) patients were HBsAg positive without any difference according to HIV type (7.9% in HIV-1, 7.2% in HIV-1&2 dually reactive and 9.4% in HIV-2; p = 0.61). In multivariate logistic analysis, age ≤ 30 years old (adjusted odds ratio [aOR] 5.00, 95% CI 1.96-12.76), age between 31 and 49 years old (aOR 1.78, 95% CI 1.00-2.21) and male gender (aOR 2.15, 95% CI 1.25-3.69) were associated with HBsAg positivity. HBV DNA testing was performed in 36 patients with blood sample available (25 on ART) and 8 (22.2%) had detectable HBV DNA. Among the HBsAg-positive individuals, 14.9% (95% CI 7.4-25.7) were also positive for anti-HDV antibody without any difference according to HIV type (28.6% in HIV-1, 14.3% in HIV-2 and 0.0% in HIV-1&2 dually reactive; p = 0.15). CONCLUSION: HBV and HBV/HDV co-infection are common in West Africa, irrespective of HIV type. Therefore, screening for both viruses should be systematically performed to allow a better management of HIV-infected patients. Follow-up studies are necessary to determine the impact of these two viruses on HIV infection.

Boosted protease inhibitor monotherapy versus boosted protease inhibitor plus lamivudine dual therapy as second-line maintenance treatment for HIV-1-infected patients in sub-Saharan Africa (ANRS12 286/MOBIDIP): a multicentre, randomised, parallel, open-label, superiority trial.

BACKGROUND: 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). METHODS: 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. FINDINGS: 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; p<0·0001) 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). INTERPRETATION: 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. FUNDING: Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

Short Communication: High Viral Load and Multidrug Resistance Due to Late Switch to Second-Line Regimens Could Be a Major Obstacle to Reach the 90-90-90 UNAIDS Objectives in Sub-Saharan Africa.

In the context of lifelong antiretroviral treatment (ART) as early as possible and to end the HIV/AIDS epidemic as a public health treat by 2030, it is important to evaluate the potential risk of transmission of HIV-1 drug resistance (HIVDR) in resource-limited countries (RLCs). Since HIV transmission is driven by HIV-1 RNA viral load (VL), we studied the association between plasma VL and HIVDR profiles in 451 adults failing first-line ART from the 2LADY-ANRS12169/EDCTP trial in Burkina Faso, Cameroon, and Senegal. Median duration on first-line ART was 49 months (IQR: 33-69) and 91% patients were asymptomatic. Genotypic drug resistance testing was successful for 446 patients and 98.7% of them were resistant to at least one of the first-line drugs; 40.6% and 55.8% were resistant to two or three drugs of their ongoing first-line ART, respectively. The median VL was higher in patients with HIVDR to all ongoing first-line drugs than in those still susceptible to at least one drug; 4.7 log10 copies/ml (IQR: 4.3-5.2) versus 4.2 log10 copies/ml (IQR: 3.7-4.7), respectively (p < .001). The proportion of patients with HIVDR to all ongoing first-line drugs was highest (77.9% [95/122]) in patients with VL >5.0 log10 copies/ml. High rates of cross-resistance to other nucleoside reverse-transcriptase inhibitors were observed and were also highest in patients with high VL. Without improvement of patient monitoring to avoid late switch to second-line regimens, a potential new epidemic caused by HIVDR strains could emerge in sub-Saharan Africa and compromise all efforts to reach 90-90-90 UNAIDS objective by 2020.

Pregnancy rate and birth outcomes among women receiving antiretroviral therapy in Burkina Faso: a retrospective cohort study.

INTRODUCTION: In Sub-Saharan Africa, few studies reported pregnancy incidence and outcomes in women taking antiretroviral therapy (ART). This survey aims to estimate the incidence and outcomes of pregnancy in a cohort of HIV positive women initiating ART in Bobo-Dioulasso, Burkina Faso. METHODS: We carried out a retrospective cohort study. We selected women in childbearing age initiating ART and followed up in Bobo-Dioulasso teaching hospital between January 2005 and June 2011. The incidence of pregnancies during follow-up was calculated. Childbirth was defined by the expulsion of a fetus after 22 weeks of amenorrhea. Before this term, it is an abortion. Childbirth is said premature if it occurs before 37 weeks of gestation, to term if it occurs between the 38th and the 42nd week. The annual age-standardized fertility rates were calculated using the baseline population from the 2010 demographic and health survey (DHS) in Burkina Faso. RESULTS: A total of 1,763 women of childbearing age under ART were included in the study. They ranged between 18 and 48 years old with a median of 35 years old. A total of 222 pregnancies were observed during 4639 women-years of follow-up, corresponding to an incidence density of 5 pregnancies for 100 women-years (95% CI: 4.2-5.5). Among the 222 pregnancies recorded, 9(4.0%) ended with abortion, 205(92.4%) with childbirth (including 15 premature childbirths); the outcome of 8(3.6%) pregnancies were unknown abortion. Live birth and stillborn rates were 94.0% (193/205) and 6.0% respectively. The standard fertility rate in our cohort was 45 live births for 1,000 women-years. The general decrease in fertility rates was 66.0% among women infected with HIV compared to the overall population. CONCLUSION: This study shows a low pregnancy incidence among women initiating ART as compared to their peers from the general population. Pregnancies that occurred during ART generally end with live births. Care packages for HIV infected women of childbearing age must include reproductive health services to better address this issue.

Re-testing and misclassification of HIV-2 and HIV-1&2 dually reactive patients among the HIV-2 cohort of the West African Database to evaluate AIDS collaboration.

INTRODUCTION: West Africa is characterized by the circulation of HIV-1 and HIV-2. The laboratory diagnosis of these two infections as well as the choice of a first-line antiretroviral therapy (ART) is challenging, considering the limited access to second-line regimens. This study aimed at confirming the classification of HIV-2 and HIV-1&2 dually reactive patients followed up in the HIV-2 cohort of the West African Database to evaluate AIDS collaboration. METHOD: A cross-sectional survey was conducted from March to December 2012 in Burkina Faso, Côte d'Ivoire and Mali among patients classified as HIV-2 or HIV-1&2 dually reactive according to the national HIV testing algorithms. A 5-ml blood sample was collected from each patient and tested in a single reference laboratory in Côte d'Ivoire (CeDReS, Abidjan) with two immuno-enzymatic tests: ImmunoCombII® (HIV-1&2 ImmunoComb BiSpot - Alere) and an in-house ELISA test, approved by the French National AIDS and hepatitis Research Agency (ANRS). RESULTS: A total of 547 patients were included; 57% of them were initially classified as HIV-2 and 43% as HIV-1&2 dually reactive. Half of the patients had CD4≥500 cells/mm(3) and 68.6% were on ART. Of the 312 patients initially classified as HIV-2, 267 (85.7%) were confirmed as HIV-2 with ImmunoCombII® and in-house ELISA while 16 (5.1%) and 9 (2.9%) were reclassified as HIV-1 and HIV-1&2, respectively (Kappa=0.69; p<0.001). Among the 235 patients initially classified as HIV-1&2 dually reactive, only 54 (23.0%) were confirmed as dually reactive with ImmunoCombII® and in-house ELISA, while 103 (43.8%) and 33 (14.0%) were reclassified as HIV-1 and HIV-2 mono-infected, respectively (kappa= 0.70; p<0.001). Overall, 300 samples (54.8%) were concordantly classified as HIV-2, 63 (11.5%) as HIV-1&2 dually reactive and 119 (21.8%) as HIV-1 (kappa=0.79; p<0.001). The two tests gave discordant results for 65 samples (11.9%). CONCLUSIONS: Patients with HIV-2 mono-infection are correctly discriminated by the national algorithms used in West African countries. HIV-1&2 dually reactive patients should be systematically investigated, with a standardized algorithm using more accurate tests, before initiating ART as at least 4 out of 10 of them could initiate an effective first-line ART for HIV-1 and optimize their second-line treatment options.

The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso.

INTRODUCTION: Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. METHODS: We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. RESULTS: Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77-3.60; p<0.001). CONCLUSIONS: Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to determine the causes for their vulnerability in order to optimize HIV care. From now on, efforts should be made to support the adherence of men to ART in the African setting.

Characteristics of HIV-2 and HIV-1/HIV-2 Dually Seropositive Adults in West Africa Presenting for Care and Antiretroviral Therapy: The IeDEA-West Africa HIV-2 Cohort Study.

BACKGROUND: HIV-2 is endemic in West Africa. There is a lack of evidence-based guidelines on the diagnosis, management and antiretroviral therapy (ART) for HIV-2 or HIV-1/HIV-2 dual infections. Because of these issues, we designed a West African collaborative cohort for HIV-2 infection within the framework of the International epidemiological Databases to Evaluate AIDS (IeDEA). METHODS: We collected data on all HIV-2 and HIV-1/HIV-2 dually seropositive patients (both ARV-naive and starting ART) and followed-up in clinical centres in the IeDEA-WA network including a total of 13 clinics in five countries: Benin, Burkina-Faso Côte d'Ivoire, Mali, and Senegal, in the West Africa region. RESULTS: Data was merged for 1,754 patients (56% female), including 1,021 HIV-2 infected patients (551 on ART) and 733 dually seropositive for both HIV-1 and HIV 2 (463 on ART). At ART initiation, the median age of HIV-2 patients was 45.3 years, IQR: (38.3-51.7) and 42.4 years, IQR (37.0-47.3) for dually seropositive patients (p = 0.048). Overall, 16.7% of HIV-2 patients on ART had an advanced clinical stage (WHO IV or CDC-C). The median CD4 count at the ART initiation is 166 cells/mm(3), IQR (83-247) among HIV-2 infected patients and 146 cells/mm(3), IQR (55-249) among dually seropositive patients. Overall, in ART-treated patients, the CD4 count increased 126 cells/mm(3) after 24 months on ART for HIV-2 patients and 169 cells/mm(3) for dually seropositive patients. Of 551 HIV-2 patients on ART, 5.8% died and 10.2% were lost to follow-up during the median time on ART of 2.4 years, IQR (0.7-4.3). CONCLUSIONS: This large multi-country study of HIV-2 and HIV-1/HIV-2 dual infection in West Africa suggests that routine clinical care is less than optimal and that management and treatment of HIV-2 could be further informed by ongoing studies and randomized clinical trials in this population.

Analysis of the diversity of the HIV-1 pol gene and drug resistance associated changes among drug-naïve patients in Burkina Faso.

A cross-sectional study was undertaken among drug-naïve HIV patients at the University Hospital in Ouagadougou shortly before and after the introduction of large-scale antiretroviral therapy (ART) in Burkina Faso. Baseline clinical and virological data as well as protease (PR) and 5' reverse transcriptase (RT) sequences from 104 HIV infected patients were analyzed. Genotypic classification revealed the following subtypes and recombinant forms: CRF06_cpx, n = 46 (44.2%); CRF02_AG, n = 39 (37.5%); subtype A, n = 4 (3.8%); CRF09_cpx, n = 2 (1.9%); and unclassified, n = 13 (12.5%). Bootstrap analysis of CRF02_AG and CRF06_cpx viruses showed that >80% had a similar structure to their respective prototypes. The prevalence of primary drug resistance mutations was 12.5%, all mutations arising in the RT sequences in accordance with the dominance of this drug class in Burkina Faso. The mutations were distributed as follows: NRTI (10.6%): M41L (n = 2), D67N (n = 2), K70K/E (n = 2), L210W (n = 1), T215S/Y (n = 2), and K219K/Q (n = 2); NNRTI (6.1%): K103K/N (n = 2), Y181C (n = 2), G190G/A (n = 1), and P236P/L (n = 1). Subtype specific secondary polymorphisms such as K20I and M36I in the PR were observed in almost all patients. Drug resistance mutations occurred at similar frequencies (12.8% and 10.8%, respectively) among patients infected with CRF02_AG and CRF06_cpx. Some subtype specific polymorphisms were observed within important HLA epitopes, including B35, B7, and A2 in the RT, and A*6802 in the PR sequences. The observed resistance mutations are most likely to have been transmitted based on the timing of the study but prior undocumented use of ART cannot be excluded.

HIV drug resistance pattern among HAART-exposed patients with suboptimal virological response in Ouagadougou, Burkina Faso.

OBJECTIVE: Determine the pattern of drug resistance among HIV infected drug exposed patients failing therapy in Ouagadougou, Burkina Faso. METHODS: The protease (PR) and reverse transcriptase (RT) of 87 samples from 75 treatment exposed HIV infected patients failing therapy were PCR amplified, sequenced, subtyped and analyzed for the presence of drug resistance mutations. RESULTS: The most common drugs used were 3TC, AZT (or d4T) and EFV. The dominant subtypes were CRF06_cpx (48%) and CRF02_AG (40%). The prevalence of resistance mutations among patients failing therapy was: PR inhibitors (PI), 40%; non-nucleoside RT-inhibitors (NNRTI), 76% and nucleoside RT-inhibitors (NRTI), 85%. Dominant mutations included M46I (37%), 154V (26%), V82A/T/F (30%) in PR; K103N (44%), G190A/S (16%) and T215F/Y (48%) (NRTIs) in RT. Some resistance mutations, notably D67N/G, K70R and L210W (thymidine analogue mutations-TAMs); K101E, V179E in RT, 154V, V82A/T/F and L90M in PR were significantly higher among CRF06_cpx than CRF02_AG strains (P < 0.05). Although not significant, other TAMs (M41L, T215F/Y, K219Q/E) also occurred more frequently among CRF06_cpx strains as well. CONCLUSION: There is a high prevalence of drug resistance mutations among ARV exposed patients in Burkina Faso with an unexpected subtype-specific difference. Validation of this result will require larger sample sizes and in vitro drug susceptibility studies with CRF06_cpx strains.