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This cross-sectional study describes the clinical characteristics and outcomes of patients with COVID-19 infection in Gabon from March to June 2020., Key Points Question What were the epidemiologic and clinical aspects of patients with COVID-19 infection in the Armed Forces Hospital in Libreville, Gabon, from March to June 2020? Findings In this cross-sectional study of 837 patients with COVID-19 in Gabon, 63% had no symptoms. Severity of disease and mortality were associated with advanced age and advanced stage of lung damage. Meaning Findings from this observational study provide preliminary data for use in future epidemiologic studies of COVID-19 in Gabon., Importance Since the emergence of COVID-19 in central China, sub-Saharan African countries, with the exception of South Africa, have been relatively spared during the COVID-19 pandemic. Consequently, few descriptive studies from this region are available. Objective To describe the clinical characteristics and outcomes of patients with COVID-19 infection in Gabon, from March to June 2020. Design, Setting, and Participants A single-center, cross-sectional study of 837 patients with COVID-19 was conducted from March to June 2020 in the Armed Forces Hospital in Libreville, Gabon. Main Outcomes and Measures Demographic and clinical characteristics and imaging findings of hospitalized patients with COVID-19. Results Of the 837 patients enrolled, 572 (68.3%) were men, and 264 (31.5%) were women (male to female ratio, 2:1); the median (interquartile range [IQR]) age was 35 (30-45) years (mean [SD] age, 38.0 [12.2] years. The mortality rate associated with COVID-19 was low (1.4%). Of these 837 patients, 524 (62.6%) were categorized as having no symptoms, 282 (33.7%) as having mild symptoms, and 31 (3.7%) as having severe symptoms. Patients with severe symptoms were older (mean [SD] age, 46.1 [14.7] years) than patients with mild symptoms (mean [SD] age, 41.3 [12.5] years) and those with no symptoms (mean [SD] age, 35.7 [11.3] years) (Kruskal-Wallis χ22 = 53.5; P

The objective of this study was to determine the rates of virological failure (VF) and HIV drug resistance (HIVDR) amongst adolescents on antiretroviral Therapy (ART). A retrospectively designed study was conducted in 10 healthcare centers for adolescents living with HIV (ALHIV) in the two main cities of Cameroon (Yaoundé and Douala), from November 2018 to May 2019. Sociodemographic, clinical, therapeutic and laboratory parameters were collected from medical records. All enrolled ALHIV had viral load (VL) measurements following the national guidelines. All patients with a VL ≥ 1000 copies/ml were called to perform genotyping tests. The chi-square test was used to determine the factors associated with VF. Out of the 1316 medical records of ALHIV, we included 1083 ALHIV having a VL result. Among them, 276 (25.5%) were experiencing VF, and VF was significantly higher in ALHIV with suboptimal adherence (p

Introduction Human T-cell lymphotrophic virus type-1 (HTLV-1) and human immunodeficiency virus (HIV-1) co-infection occur in many populations. People living with HIV-1 and infected with HTLV-1 seem more likely to progress rapidly towards AIDS. Both HTLV-1 and HIV-1 are endemic in Gabon (Central Africa). We investigated HTLV-1 and HIV-1 co-infection in the Haut-Ogooué province, and assessed factors that may favor the rapid evolution and progression to AIDS in co-infected patients. Methods Plasma samples from HTLV-1 patients were tested using ELISA, and positive samples were then tested by western blot assay (WB). We used the polymerase chain reaction to detect HTLV-1 Tax/Rex genes using DNA extracted from the buffy coat of ELISA-positives samples. Results We recruited 299 individuals (mean age 46 years) including 90 (30%) men and 209 (70%) women, all of whom are under treatment at the Ambulatory Treatment Centre of the province. Of these, 45 were ELISA HTLV-1/2 seropositive. According to WB criteria, 21 of 45 were confirmed positive: 20 were HTLV-1 (44%), 1 was HTLV-1/2 (2%), 2 were indeterminate (4%) and 22 were seronegative (49%). PCR results showed that 23 individuals were positive for the Tax/Rex region. Considering both serological and molecular assays, the prevalence of HTLV-1 infection was estimated at 7.7%. Being a woman and increasing age were found to be independent risk factors for co-infection. Mean CD4+ cell counts were higher in HTLV-1/HIV-1 co-infected (578.1 (± 340.8) cells/mm3) than in HIV-1 mono-infected (481.0 (± 299.0) cells/mm3) Individuals. Similarly, the mean HIV-1 viral load was Log 3.0 (± 1.6) copies/ml in mono-infected and Log 2.3 (± 0.7) copies/ml in coinfected individuals. Conclusion We described an overall high prevalence of HTLV-1/HIV-1 co-infection in Gabon. Our findings stress the need of strategies to prevent and manage these co-infections.

OBJECTIVE We aimed to assess the frequency of tenofovir (TDF) resistance in people failing tenofovir/lamivudine or emtricitabine (XTC)/nonnucleotide reverse-transcriptase inhibitor-based first-line antiretroviral treatment (ART) using data from 15 nationally representative surveys of HIV drug resistance conducted between 2014 and 2018 in Cameroon, Guatemala, Honduras, Nicaragua, Senegal, Uganda, Vietnam and Zambia. METHODS Prevalence of nucleoside reverse-transcriptase inhibitor resistance among participants with virological nonsuppression (viral load ≥1000 copies/ml) who had received TDF-based ART for 12-24 months (early ART group) and at least 40 months (long-term ART group) was assessed using Sanger sequencing and resistance was interpreted using the Stanford HIVdb algorithm. For each group, we estimated a pooled prevalence using random effect meta-analysis. RESULTS Of 4677 participants enrolled in the surveys, 640 (13.7%) had virological nonsuppression, 431 (67.3%) were successfully genotyped and were included in the analysis; of those, 60.3% (260) were participants in the early ART group. Overall, 39.1, 57.9, 38.5 and 3.6% patients in the early ART group and 42.9, 69.3, 42.9 and 10.0% patients on long-term ART had resistance to TDF, XTC, TDF + XTC and TDF + XTC + zidovudine, respectively. Overall, tenofovir resistance was mainly due to K65R or K70E/G/N/A/S/T/Y115F mutations (79%) but also due to thymidine analogue mutations (21%) which arise from exposure to thymidine analogues but causing cross-resistance to TDF. CONCLUSION Dual resistance to TDF + XTC occurred in more than 40% of the people with viral nonsuppression receiving tenofovir-based first-line ART, supporting WHO recommendation to optimize the nucleoside backbone in second-line treatment and cautioning against single drug substitutions in people with unsuppressed viral load.

Background Pretreatment HIV drug resistance (PDR) has the potential to affect treatment outcome and mortality. We present here the first nationally representative PDR study conducted in Cameroon. Methods From February to July 2015, HIV-infected ART initiators were recruited from 24 randomly selected clinics situated in both urban and rural regions. Dried blood spot specimens were collected from study participants at these clinics and centralized in a reference laboratory in Yaounde, Cameroon, for drug resistance testing. HIV drug resistance mutations were identified using the Stanford algorithm. Results Overall, from the 379 participants recruited, 321 pol sequences were successfully interpreted. Two hundred and five sequences were from patients attending urban ART clinics and 116 from patients seen at rural facilities. Nine percent of sequences (29/321) were from participants reporting previous exposure to antiretrovirals. PDR prevalence among all initiators was 10.4% (95% CI 5.4%-19.1%), with 14.2% (95% CI 6.6%-27.9%) reported in urban areas and 4.3% (95% CI 1.2%-14.3%) in rural areas. Among participants with no prior exposure to antiretrovirals, PDR prevalence was 10.4% (95% CI 4.7%-21.5%) overall, with 13.5% (95% CI 5.1%-31.5%) and 5.3% (95% CI 1.4%-17.5%) reported in urban and rural areas, respectively. Conclusions Our findings indicate that at least 10% of patients initiating ART in Cameroon carry viruses with PDR and may be at risk of premature ART failure. The high level of NNRTI-associated resistance is of particular concern and supports introduction of drugs with a higher genetic barrier to resistance.

Use of dolutegravir-based first-line antiretroviral therapy (ART) in response to rising levels of pretreatment HIV drug resistance (PDR) to non-nucleoside reverse transcriptase inhibitors (NNRTIs) may be limited, given safety concerns for birth defects in women of child-bearing potential. Pooled data from 11 nationally representative surveys show that NNRTI PDR in women is nearly twice that in men, exceeding 10% in 8 of 11 countries monitored, suggesting the urgent need for a non-NNRTI-based ART regimen in this population.

International audience; 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 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.

BackgroundLittle is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence.MethodsWe performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96.ResultsForty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline.ConclusionsOur data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed.Clinical Trials RegistrationNCT00658346.

International audience; Background:ART in the developing world has moved to a new era with the WHO recommendation to test and immediately treat HIV-positive individuals. A high frequency of pretreatment HIV drug resistance (PDR) can compromise ART efficacy. Our study presents updated estimates of PDR in seven countries from West Africa (Burkina Faso, Cameroon, Côte d'Ivoire, Mali and Togo) and Southeast Asia (Thailand and Vietnam).Methods:Eligible study participants were adult ART initiators, recruited from December 2015 to November 2016 in major ART clinics in each country. HIV drug resistance (HIVDR) tests were performed for all specimens and interpretation was done using the Stanford algorithm.Results:Overall, 1153 participants were recruited and 1020 nt sequences were generated. PDR frequency among all initiators was 15.9% (95% CI: 13.8%-18.3%) overall, ranging from 9.6% and 10.2% in Burkina Faso and Thailand, respectively, 14.7% in Vietnam, 15.4% in Mali, 16.5% in Côte d'Ivoire and 19.3% in Cameroon, to 24.6% in Togo. The prevalence of NNRTI resistance mutations was 12%; NRTI and PI PDR prevalences were 4% and 3%, respectively.Conclusions:Our study shows that in most countries PDR exceeded 10%, warranting the conduct of nationally representative surveys to confirm this trend. In the meantime, actions to prevent drug resistance, including transition from NNRTIs to more robust drug classes should be urgently implemented.

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.

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.

Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

The routine use of integrase inhibitors in sub-Saharan Africa where HIV-1 non-B viruses predominate is limited, but evaluating their effectiveness on HIV-1 subtypes and CRFs that circulate in this region is essential. We here analyzed 97 integrase sequences from HIV-1 non-B-infected individuals from African countries. Using currently available interpretation algorithms (ANRS, HIVdb, and Rega), we identified the presence of mutations at nine resistance-associated positions including L74M (3.1%), T97A (9.3%), K156N (2.1%), E157Q (5.2%), G163K (1.0%), T206S (48.5%), S230N (1.0%), D232N (1.0%), and R236K (1.0%). All but one (E157Q) were considered as accessory resistant mutation by the algorithms. E157Q identified in 5% of patients tested (5/97) was selected by the ANRS algorithm as a primary mutation, which alone can confer resistance to raltegravir. These results illustrated the need of further in vitro and clinical studies involving non-B viruses to better understand the real significance of observed mutations and harmonize interpretations.

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).

Background. The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART. Methods. Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of >= 1000 copies/mL, considered as the failure threshold, were geno-typed for drug resistance assessment. Results. Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4(+) T-cell counts at ART initiation were low (99-172 cells/mu L). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine. Conclusions. Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.

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).

International audience; With the increasing demand of HIV viral load (VL) tests in resource-limited countries (RLCs) there is a need for assays at affordable cost and able to quantify all known HIV-1 variants. VLs obtained with a recently developed open and polyvalent universal HIV-1/SIVcpz/SIVgor RT-qPCR were compared to Abbott RealTime HIV-1 assay in Cameroon. On 474 plasma samples, characterized by a wide range of VLs and a broad HIV-1 group M genetic diversity, 97.5% concordance was observed when using the lower detection limit of each assay. When using the threshold of 3.00 log10 copies/mL, according to WHO guidelines to define virological failure (VF) in RLCs, the concordance was 94.7%, 360/474 versus 339/474 patients were identified with VF with the new assay and Abbott RealTime HIV-1, respectively. Higher VLs were measured with the new assay, +0.47 log10 copies/mL (95% CI; 0.42-0.52) as shown with Bland-Altman analysis. Eleven samples from patients on VF with drug resistance were not detected by Abbott RealTime HIV-1 versus two only with the new assay. Overall, our study showed that the new assay can be easily implemented in a laboratory in RLCs with VL experience and showed good performance on a wide diversity of HIV-1 group M variants.

The human immunodeficiency virus, HIV, is characterized by a tremendously high genetic diversity, leading to the currently known circulating HIV types, groups, subtypes, and recombinant forms. HIV-1 group O is one of the most diverse forms of HIV-1 and has been so far related to Cameroon or individuals originating from Cameroon. In this study, we investigated in Cameroon, the evolution of this viral group from 2006 to 2013, in terms of prevalence, genetic diversity and public health implications. Our results confirmed the predominance of HIV-1 group M (98.5%), a very low prevalence (

Objectives: To evaluate the frequency and progression over time of the WHO-defined transmitted HIV-1 drug resistance mutations (DRMs) among antiretroviral treatment (ART)-naive HIV-1-infected patients in Cameroon. Design: We analyzed HIV-1 DRM data generated from 369 ART-naive individuals consecutively recruited between 1996 and 2007 in urban and rural areas in Cameroon. Methods: HIV-1 drug resistance genotyping was performed in the pol gene using plasma samples and surveillance DRMs were identified using the 2009 WHO-DRM list. Results: We observed in Yaounde, the capital city, an increasing prevalence of DRMs over time: 0.0% (none of 61 participants) in 1996-1999; 1.9% (one of 53 participants) in 2001; 4.1% (two of 49 participants) in 2002; and 12.3% (10 of 81 participants) in 2007. In the rural areas with more recently implemented ART programs, we found DRMs in six of 125 (4.8%) ART-naive individuals recruited in 2006-2007. DRMs identified in both areas included resistance mutations to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) that might impair the efficacy of available first-line and second-line treatments. Conclusion: This report showed an increase in transmitted DRMs in areas where antiretroviral drugs were introduced earlier, although other factors such as natural viral polymorphisms and acquired DRMs through exposure to antiretroviral cannot be totally excluded. Further surveillances are needed to confirm this evolution and inform public health policies on adequate actions to help limit the selection and transmission of drug-resistant HIV, while scaling up access to ART in developing countries.

The ViroSeq HIV-1 genotyping system is used in many African countries for drug resistance testing. In this study, we used a panel of diverse HIV-1 group M isolates circulating in Cameroon to show that the performance of this assay can be altered by the sequence variation of non-B HIV-1 strains that predominate in African settings.

Background In Africa, most HIV–HBV-coinfected patients on antiretroviral therapy (ART) receive an anti-HBV lamivudine monotherapy that has been shown in northern countries to lead to frequent emergence of drug resistance. We assessed the HBV prevalence and the rate and pattern of lamivudine-resistant HBV mutations in Cameroonian HIV-infected, ART-treated patients. Methods A cross-sectional survey was performed in 2006–2007 at the HIV/AIDS outpatient clinic of the Central Hospital in Yaoundé, Cameroon. Plasma samples were tested as appropriate for hepatitis B surface antigens, antibodies to hepatitis B core, HBV DNA, genotypes and lamivudine-resistant polymerase mutations. Results Of 552 adult patients (71% women, median age 38 years), 290 had received lamivudine-based ART for 12 months and 262 for 24 months. No patient had received tenofovir. The prevalence of hepatitis B surface antigen was 9.8%. Overall, 26% of seropositive patients had an HBV DNA level >40 IU/ml. Genotypes A and E were identified. Polymerase resistance mutations were detected in 14% and 60% of patients at months 12 and 24, respectively. Conclusions This study supports both WHO recommendations of screening for HBV before initiation of ART and of using ART containing tenofovir and either lamivudine or emtricitabine in HIV–HBV-coinfected patients in Africa.

To evaluate the risk of cross-species transmissions of SIVs from non-human primates to humans at the primate/hunter interface, a total of 2586 samples, derived from primate bushmeat representing 11 different primate species, were collected at 6 distinct remote forest sites in southeastern Cameroon and in Yaoundé, the capital city. SIV prevalences were estimated with an updated SIV lineage specific gp41 peptide ELISA covering the major part of the SIV diversity. SIV positive samples were confirmed by PCR and sequence analysis of partial pol fragments. The updated SIV ELISA showed good performance with overall sensitivity and specificity of 96% and 97.5% respectively. The overall SIV seroprevalence was low, 2.93% (76/2586) and ranged between 0.0% and 5.7% at forest sites, and reached up to 10.3% in Yaoundé. SIV infection was documented in 8 of the 11 species with significantly different prevalence rates per species: 9/859 (1.0%) in Cercopithecus nictitans, 9/864 (1.0%) Cercopithecus cephus, 10/60 (16.7%) Miopithecus ogouensis, 14/78 (17.9%) Colobus guereza, 15/37 (40.5%) Cercopithecus neglectus, 10/27 (33.3%) Mandrillus sphinx, 6/12 (50%) Cercocebus torquatus, and 3/6 (50%) Chlorocebus tantalus. No SIV infection was identified in Cercopithecus pogonias (n=293), Lophocebus albigena (n=168) and Cercocebus agilis (n=182). The SIV prevalences also seem to vary within species according to the sampling site, but most importantly, the highest SIV prevalences are observed in the primate species which represent only 8.5% of the overall primate bushmeat. The phylogenetic tree of partial pol sequences illustrates the high genetic diversity of SIVs between and within different primate species. The tree also showed some interesting features within the SIVdeb lineage suggesting phylogeographic clusters. Overall, the risk for additional cross-species transmissions is not equal throughout southern Cameroon and depends on the hunted species and SIV prevalences in each species. However, humans are still exposed to a high diversity of SIVs as illustrated by the high inter and intra SIV lineage genetic diversity.

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.

Background The rapid expansion of antiretroviral treatment in resource-limited settings is raising concerns regarding the emergence and transmission of HIV drug resistance (HIVDR). We evaluated the extent of transmission of drug-resistant HIV strains in four Central African countries: the Republic of Congo, Central African Republic, Chad and Cameroon. Methods The World Health Organization (WHO) HIVDR threshold survey was implemented in major treatment areas in each country. Pregnant women who were aged Results The prevalence of HIVDR in Brazzaville and Bangui sites could not be classified because the eligible sample number was not reached. HIVDR prevalence was low (Conclusions The moderate HIVDR prevalence found in Yaoundé and Douala indicate that efforts should be made in Cameroon to prevent HIVDR; however, additional surveys are needed to confirm this trend. This study highlighted challenges presented by the WHO methodology, such as additional costs, workload, difficulties in acquiring even small sample numbers and the necessity for better quality assurance of HIV testing and record keeping at antenatal clinics.

Our study in Cameroonian rural district hospitals showed that the immunologic and clinical failure criteria had poor performance to identify human immunodeficiency virus drug resistance in a timely manner. Switching to second-line antiretroviral therapy after 2 consecutive viral loads ≥5000 copies/mL, as recommended by the World Health Organization, appeared to be the most appropriate strategy.

OBJECTIVES: Using cohort data nested in a randomized trial conducted in Cameroon, this study aimed to investigate time trends and predictors of the susceptibility to transmitting HIV during the first 24 months of treatment. METHODS: The outcome, susceptibility to transmitting HIV, was defined as reporting inconsistent condom use and experiencing incomplete virological suppression. Mixed logistic regressions were performed to identify predictors of this outcome among 250 patients reporting to have had sexual relationships either with HIV-negative or unknown HIV status partner(s). RESULTS: Despite an initial decrease from 76% at M0 to 50% at M6, the rate of inconsistent condom use significantly increased from M12 (59%) to M24 (66%) (p = 0.017). However, the proportion of patients susceptible to transmitting HIV significantly decreased over follow-up from 76% at M0, to 50% at M6, 31% at M12 and 27% at M24 (p

Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05-1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06-1.25), North America (OR = 1.19; 95% CI: 1.12-1.26), Europe (OR = 1.07; 95% CI: 1.01-1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12-1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92-1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Background Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. Conclusions Most TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen., In this individual patient and sequence-level meta-analysis, Soo-Yon Rhee and colleagues measure regional trends in HIV-1 transmitted drug resistance prevalence and investigate the specific mutations responsible for TDR in different regions and in different virus subtypes., Editors' Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS by destroying immune system cells and leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within ten years of infection. Then, in 1996, effective antiretroviral (ARV) therapy—drug combinations that suppress HIV replication by inhibiting reverse transcriptase and other essential viral enzymes—became available. For people living in affluent countries, HIV/AIDS became a chronic condition, but because ARV therapy was expensive, HIV/AIDS remained fatal in low- and middle-income countries (LMICs). In 2003, the international community began to work towards achieving universal access to ARV therapy. Now, more than 10 million HIV-positive individuals in LMICs receive ARV therapy, usually as a fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs), such as tenofovir and lamivudine, plus a non-nucleoside reverse transcriptase inhibitor (NNRTI), such as efavirenz or nevirapine. Why Was This Study Done? The global scale-up of ARV therapy has reduced deaths from HIV/AIDS and the incidence of HIV infection in LMICs, but the development of resistance to ARV therapy is threatening these advances. HIV rapidly accumulates genetic changes (mutations), some of which make HIV resistant to ARV therapy. Up to 30% of patients receiving a fixed-dose NRTI/NNRTI combination develop virological failure, and a high proportion of these patients develop mutations associated with resistance to the ARVs in their regimen. Moreover, the proportion of newly infected, ARV-naïve individuals with transmitted drug resistance (TDR) is also increasing. Organizations involved in HIV/AIDS control need to understand the regional and temporal mutational patterns of TDR to inform the development of guidelines for first-line ARV therapy and of inexpensive resistance mutation assays for use in LMICs. Here, using a statistical approach called meta-analysis to combine information from individual patients about the resistance mutations they carry, the researchers investigate the molecular epidemiology of TDR (the patterns of molecular changes underlying TDR in populations) and identify the HIV drug-resistance mutations most responsible for TDR in different world regions. What Did the Researchers Do and Find? The researchers identified 287 studies published between 2000 and 2013 from 111 countries that included the reverse transcriptase sequences of HIV viruses from 50,870 ARV-naïve, HIV-positive individuals. The researchers analyzed each virus sequence for the presence of 93 surveillance drug-resistance mutations (SDRMs) previously shown to be specific indicators of TDR. Meta-analysis of these data indicated that the average overall prevalence of TDR (the proportion of ARV-naïve, HIV-positive individuals infected with a virus carrying one or more SDRMs) ranged from 2.8% in sub-Saharan Africa to 11.5% in North America. In sub-Saharan Africa, the odds (chance) of TDR increased 1.09-fold per year following national ARV scale-up; this increase was attributable to an increase in NRTI- and NNRTI-associated resistance. By contrast, in LMICs in south/southeast Asia, the odds of TDR remained unchanged following ARV scale-up. In Latin America/Caribbean, North America, Europe, and upper-income Asian countries, the odds of TDR have increased by around 1.10-fold per year since 1995, mainly as a result of increased NNRTI resistance. Four NNRTI-associated and 16 NRTI-associated SDRMs accounted for most NNRTI- and NRTI-associated TDR, respectively, in all regions. Notably, in sub-Saharan Africa and south/southeast Asia, most of the NNRTI-associated SDRMs detected were associated with high-level resistance to nevirapine or efavirenz. Finally, the researchers report that 95% of TDR viruses in sub-Saharan Africa and south/southeast Asia were unrelated and had therefore arisen independently. What Do These Findings Mean? Because many drug-resistance mutations reduce HIV’s fitness and tend to be lost rapidly in individuals not exposed to ARV therapy, differences among the datasets used in this meta-analysis with respect to how long each ARV-naïve patient had been infected with HIV before virus sampling may limit the accuracy of these findings. Nevertheless, the finding that most of the TDR strains detected in sub-Saharan Africa and south/southeast Asia arose independently suggests that improved patient adherence to ARV therapy and the use of ARV regimens that contain drugs to which HIV rarely develops resistance (regimens with a high genetic barrier to resistance) should reduce the generation of new ARV-resistant strains and mitigate TDR increases. In addition, the finding that a few NNRTI-resistance mutations were responsible for most cases of transmitted high-level resistance suggests that an inexpensive assay that detects these specific mutations may be useful for pre-therapy screening in LMICs with high TDR levels. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001810. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with HIV/AIDS Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on antiretroviral drugs and on universal access to ARV therapy; Avert also provides personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of antiretroviral therapy for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it, including progress towards universal access to antiretroviral therapy The Stanford University HIV Drug Resistance Database includes information about surveillance drug-resistant mutations (SDRMs) and an interactive map displaying HIV drug resistance in ARV-naïve populations

The increasing prevalence of acquired and transmitted HIV-1 drug resistance is an obstacle to successful antiretroviral therapy (ART) in the low- and middle-income countries (LMICs) hardest hit by the HIV-1 pandemic. Genotypic drug resistance testing could facilitate the choice of initial ART in areas with rising transmitted drug resistance (TDR) and enable care-providers to determine which individuals with virological failure (VF) on a first- or second-line ART regimen require a change in treatment. An inexpensive near point-of-care (POC) genotypic resistance test would be useful in settings where the resources, capacity, and infrastructure to perform standard genotypic drug resistance testing are limited. Such a test would be particularly useful in conjunction with the POC HIV-1 viral load tests that are currently being introduced in LMICs. A POC genotypic resistance test is likely to involve the use of allele-specific point mutation assays for detecting drug-resistance mutations (DRMs). This study proposes that two major nucleoside reverse transcriptase inhibitor (NRTI)-associated DRMs (M184V and K65R) and four major NNRTI-associated DRMs (K103N, Y181C, G190A, and V106M) would be the most useful for POC genotypic resistance testing in LMIC settings. One or more of these six DRMs was present in 61.2% of analyzed virus sequences from ART-naïve individuals with intermediate or high-level TDR and 98.8% of analyzed virus sequences from individuals on a first-line NRTI/NNRTI-containing regimen with intermediate or high-level acquired drug resistance. The detection of one or more of these DRMs in an ART-naïve individual or in a individual with VF on a first-line NRTI/NNRTI-containing regimen may be considered an indication for a protease inhibitor (PI)-containing regimen or closer virological monitoring based on cost-effectiveness or country policy.

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.

L'epidemiologie de l'infection par le virus herpes humain de type 8 (HHV8) associee a celle a VIH, reste encore meconnue au Cameroun, bien que le pays soit considere comme une zone endemique pour ces deux virus. L’objectif de ce travail etait de ressortir le profil de la seroprevalence du HHV8 au sein de notre population d'etude. 57 personnes ont ete recrutees a l'Hopital General de Yaounde et suivies sur une duree 12 mois. Des anticorps IgG anti-HHV8 ont ete determines par ELISA. Des parametres autres, tels que l'âge, le sexe, le stade des maladies (SK et VIH/SIDA), le protocole ARV, ainsi que les taux de CD4 ont ete utilises pour determiner les variables associees a la seropositivite au HHV8. Cette association a ete evaluee par le test khi carre. La seroprevalence du HHV8 etait de 90% dans notre population en debut d'etude et de 74% douze mois plus tard, une seroprevalence qui restait elevee quelque soit le profil clinique, la tranche d'âge, le sexe ou le taux de CD4+ de l'individu. Aucune variable de l'etude n'etait significativement associee a la seropositivite du HHV8. Le virus HHV8 semblait circuler au sein de notre population d'etude. Cependant l'on constate, douze mois plus tard, l'absence de manifestations cliniques du SK chez les patients VIH+ positifs, malgre des titres tres eleves en IgG anti-HHV8.

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

Genotypic drug resistance interpretation algorithms have been developed on patients infected with HIV-1 subtype B to interpret complex patterns of mutations. As non-B strains are characterised by the natural presence of several resistance-related mutations, we examined to what extent this might result in interalgorithm discordances in naive and treated patients. We compared the prediction by three algorithms (ANRS, Stanford and Rega) of drug susceptibilities to diverse HIV-1 strains from 272 naive and 156 treated patients. In naive patients, higher levels of interalgorithm discordance were observed for predictions of protease inhibitor (0.60-39%) than for predictions of reverse transcriptase inhibitor susceptibility (0-4%). The main reason for discordant protease inhibitor interpretation was the presence of resistance mutations that were natural protease polymorphisms. In contrast, in the treated patients, more interalgorithm discordances were observed for predictions of reverse transcriptase inhibitor (5-48%) than protease inhibitor susceptibilities (10-31%). Discordances were related to disagreement between the intermediate and susceptible scores, the intermediate and resistant scores and the interpretations of complex mutation patterns, related to cross-resistance and antagonistic interactions.

Recently T-20 or enfuvirtide, the first drug of a new class of antiretrovirals targeting the entry stage of the virus life cycle, has been clinically approved. Enfuvirtide is a peptide derived from the HR2 region of the transmembrane glycoprotein from the HXB2 HIV-1 subtype B prototype strain that binds to the HR1 region. Drug resistance seems to occur in the HR1 region between amino acids 36 and 45. We examined to what extent this region is conserved in 184 non-B strains from Cameroon: 132 (71.7%) CRF02-AG, 14 (7.6%) subtype A, 11 (5.9%) F2, 9 (4.8%) subtype D, 8 (4.3%) subtype G, 4 (2.1%) CRF01-AE, 4 (2.1%) CRF11-cpx, and 2 (1.1%) CRF06-cpx. Among the 184 strains studied, no amino acid mutation was found in the highly conserved three amino acid motif at codons 36-38 (GIV) that are important determinants of viral susceptibility to enfuvirtide. Other common substitutions like Q40H and N42T were also absent. The N42S polymorphism was present in 148 (80.4%) strains. Analysis of the HR2 domain, from which the peptide is derived, indicated a much greater genetic variability as compared to HR1.

The performance of 4 rapid and simple assays: Camstix-HIV 1+2 (Camdiagnostix, Yaounde, Cameroon); Determine HIV 1+2+0 (Abbott Laboratories, Tokyo, Japan); Genie II HIV-1/HIV-2 (Bio-Rad, Marnes la Coquette, France); ImmunoComb II HIV 1 & 2 BiSpot (Orgenics, Yavne, Israel); and 2 fourth-generation ELISAs: Enzygnost HIV Integral (Dade Behring, Marburg, Germany) and Genscreen plus HIV Ag-Ab (Bio-Rad, Marnes la Coquette, France) currently used in Cameroon to detect HIV infections were evaluated on a local serum panel. A total of 503 samples were collected, using the Camstix-HIV 1+2 assay. Overall, 280 samples were confirmed HIV positive, 181 were negative, and 42 were indeterminate. All positive samples belonged to group M: CRF02_AG (73.5%), A1 (7.1%), A2 (1.2%), G (4.7%), F2 (5.1%), D (1.6%), CRF11 (1.6%), CRF06 (1.2%), and CRF01_AE (1.6%). Sensitivity, specificity, test efficiency, and positive and negative predictive values were calculated both including and excluding indeterminate samples. Except for Genie II and ImmunoComb II (98.9 and 99.3%, respectively), sensitivities were 100% for the remaining 4 tests. Specificities, efficiencies, and positive predictive values of all assays were negatively affected by the addition of HIV-indeterminate samples in the calculations. These data show the importance of prior test evaluations on local serum panels and in field conditions before a national policy for HIV screening is decided on and stress also the need to use tests and algorithms that can reduce the high number of HIV-indeterminate results in Africa.

Objectives An open-label randomized trial (DAYANA) was conducted in sub-Saharan settings to evaluate four different regimens containing tenofovir disoproxil fumarate as first-line treatment for HIV infection. The objectives of the present substudy were to assess the relationship between trough concentrations of tenofovir in plasma collected after 24 h (C24) and estimated glomerular filtration rates (eGFR) calculated by the different formulae that are available. Methods The criteria for eligibility were those of the DAYANA trial, recruiting naive patients. The four tenofovir regimens were: Group 1, tenofovir/emtricitabine/nevirapine; Group 2, tenofovir/lopinavir/ritonavir; Group 3, tenofovir/emtricitabine/zidovudine; and Group 4, tenofovir/emtricitabine/efavirenz. The C24 of tenofovir was determined using LC-MS/MS. The eGFR was calculated using the Cockcroft–Gault, Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae. Results The median C24 of tenofovir was 42 ng/mL. The C24 of tenofovir was higher with lopinavir/ritonavir than with the other three regimens: at Week 4, 84 ng/mL versus 25 ng/mL; and at Week 48, 81 ng/mL versus 52 ng/mL. The baseline merged eGFR was 98.2 mL/min/1.73 m2 with the CKD-EPI equation. Only the mean changes in eGFR in Group 2 differed from the absolute value of zero (−8.2 mL/min/1.73 m2) with the CKD-EPI equation between baseline and Week 48. The Cockcroft–Gault formula is inappropriate for these African patients because it underestimated the baseline eGFR and overestimated the changes in eGFR between baseline and Week 48. Conclusions In this population of mostly female HIV-1-infected African patients, tenofovir plasma overexposure was associated with PI/ritonavir and a time-dependent decrease in eGFR, probably via an inhibition of MRP2/MRP4 efflux transporters. The close monitoring over time of the eGFR using MDRD or CKD-EPI calculations and by using other biomarkers of renal disorder should be proposed as an alternative to therapeutic drug monitoring in resource-limited countries.

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

Background Rapid scale-up of antiretroviral therapy (ART) and limited access to genotyping assays in low-resource settings (LRS) are inevitably accompanied by an increasing risk of HIV drug resistance (HIVDR). The current study aims to evaluate early warning indicators (EWI) as an efficient strategy to limit the development and spread of preventable HIVDR in these settings, in order to sustain the performance of national antiretroviral therapy (ART) rollout programmes. Methods Surveys were conducted in 2008, 2009 and 2010 within 10 Cameroonian ART clinics, based on five HIVDR EWIs: (1) Good prescribing practices; (2) Patient lost to follow-up; (3) Patient retention on first line ART; (4) On-time drug pick-up; (5) Continuous drug supply. Analysis was performed as per the World Health Organisation (WHO) protocol. Results An overall decreasing performance of the national ART programme was observed from 2008 to 2010: EWI1 (100% to 70%); EWI2 (40% to 20%); EWI3 (70% to 0%); EWI4 (0% throughout); EWI5 (90% to 40%). Thus, prescribing practices (EWI1) were in conformity with national guidelines, while patient adherence (EWI2, EWI3, and EWI4) and drug supply (EWI5) were lower overtime; with a heavy workload (median ratio ≈1/64 staff/patients) and community disengagement observed all over the study sites. Conclusions In order to limit risks of HIVDR emergence in poor settings like Cameroon, continuous drug supply, community empowerment to support adherence, and probably a reduction in workload by task shifting, are the potential urgent measures to be undertaken. Such evidence-based interventions, rapidly generated and less costly, would be relevant in limiting the spread of preventable HIVDR and in sustaining the performance of ART programmes in LRS.

Background: Task shifting to nurses for antiretroviral therapy (ART) is promoted by the World Health Organization to compensate for the severe shortage of physicians in Africa. We assessed the effectiveness of task shifting from physicians to nurses in rural district hospitals in Cameroon. Methods: We performed a cohort study using data from the Stratall trial, designed to assess monitoring strategies in 2006-2010. ART-naive patients were followed up for 24 months after treatment initiation. Clinical visits were performed by nurses or physicians. We assessed the associations between the consultant ratio (ie, the ratio of the number of nurse-led visits to the number of physician-led visits) and HIV virological success, CD4 recovery, mortality, and disease progression to death or to the World Health Organization clinical stage 4 in multivariate analyses. Results: Of the 4141 clinical visits performed in 459 patients (70.6% female, median age 37 years), a quarter was task shifted to nurses. The consultant ratio was not significantly associated with virological success [odds ratio 1.00, 95% confidence interval (CI): 0.59 to 1.72, P = 0.990], CD4 recovery (coefficient 23.6, 95% CI: 235.6; 28.5, P = 0.827), mortality (time ratio 1.39, 95% CI: 0.27 to 7.06, P = 0.693), or disease progression (time ratio 1.60, 95% CI: 0.35 to 7.37, P = 0.543). Conclusions: This study brings important evidence about the comparability of ART-related outcomes between HIV models of care based on physicians or nurses in resource-limited settings. Investing in nursing resources for the management of noncomplex patients should help reduce costs and patient waiting lists while freeing up physician time for the management of complex cases, for mentoring and supervision activities, and for other health interventions.

Although antiretroviral treatment availability has improved, the virological monitoring of patients remains largely uneven across regions. In addition, viral quantification tests are suffering from human immunodeficiency virus type 1 (HIV-1) genetic diversity, fueled by the emergence of new recombinants and of lentiviruses from nonhuman primates. We developed a real-time reverse transcription-PCR (RT-PCR) assay that is relatively inexpensive and able to detect and quantify all circulating forms of HIV-1 and its simian immunodeficiency virus (SIV) precursors, SIVcpz and SIVgor. Primers and a probe were designed to detect all variants of the HIV-1/SIVcpz/SIVgor lineage. HIV-1 M plasma ( n = 190; 1.68 to 7.78 log 10 copies/ml) representing eight subtypes, nine circulating recombinant forms, and 21 unique recombinant forms were tested. The mean PCR efficiency was 99%, with low coefficients of intra- and interassay variation (10 copies/ml, with a 200-μl plasma volume. On the studied range, the specificity and the analytical sensitivity were 100 and 97.4%, respectively. The viral loads were highly correlated ( r = 0.95, P < 0.0001) with the reference method (generic HIV assay; Biocentric) and had no systematic difference, irrespective of genotype. Furthermore, 22 HIV-1 O plasmas were screened and were better quantified compared to the gold-standard RealTime HIV-1 assay (Abbott), including four samples that were only quantified by our assay. Finally, we could quantify SIVcpzPtt and SIVcpzPts from chimpanzee plasma ( n = 5) and amplify SIVcpz and SIVgor from feces. Thus, the newly developed real-time RT-PCR assay detects and quantifies strains from the HIV-1/SIVcpz/SIVgor lineage, including a wide diversity of group M strains and HIV-1 O. It can therefore be useful in geographical areas of high HIV diversity and at risk for the emergence of new HIV variants.

The global scale-up of antiretroviral (ARV) therapy has dramatically reduced human immunodeficiency virus (HIV) morbidity and mortality. Stavudine (d4T) has been among the most commonly used ARVs in resource-limited settings because of its efficacy, short-term tolerability, low cost, and availability in coformulated form. However, many countries are transitioning away from d4T, mainly because of mitochondrial toxicities associated with long-term d4T use. In 2010, the World Health Organization (WHO) recommended phasing out d4T even in patients without documented virological failure [1]. There are two distinct mutational pathways of d4T resistance with different implications for zidovudine (AZT) and tenofovir (TDF) cross-resistance, the primary candidates for replacing d4T [2–4]. However, genotypic resistance testing is usually not available in the resource-limited settings where d4T-containing regimens are most commonly used. It is therefore important to determine the extent of nucleoside reverse-transcriptase inhibitor (NRTI) cross-resistance in viruses from individuals with virological failure on d4T-containing first-line therapy undergoing genotypic resistance testing. In this study, we combined genetic sequence data from 35 different studies to characterize the patterns of NRTI resistance mutations in viruses from individuals with virological failure on the 2 widely used d4T-containing ARV regimens: d4T/lamivudine(3TC)/nevirapine(NVP) and d4T/3TC/efavirenz(EFV). We also examine the effects of HIV-1 subtype, duration of therapy, and concomitant nonnucleoside reverse-transcriptase inhibitor (NNRTI) on the selection of specific mutations. We focused our analysis on NRTI resistance mutations with differential effects on the residual activity of AZT compared with TDF. The implications of these data for optimal replacement of d4T and subsequent NRTI options are discussed.

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

Background Although treatment adherence is a major challenge in sub-Saharan Africa, it is still unknown which longitudinal patterns of adherence are the most detrimental to long-term virological response to non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens. This analysis aimed to study the influence of different time patterns of adherence on virological failure after 24 months of treatment in Cameroon. Methods Antiretroviral therapy (ART) adherence data were collected using face-to-face questionnaires administered at months 1, 3, 6, 12, 18 and 24. Virological failure was defined as viral load >40 copies/ml at month 18 and/or 24. Two combined indicators of early adherence (months 1, 3 and 6) and adherence during the maintenance phase (months 12, 18 and 24) were designed to classify patients as always adherent during the early or maintenance phase, non-adherent at least once and having interrupted ART for >2 days at least once at any visit during either of these two phases. Results Virological failure occurred in 107 (42%) of the 254 patients included in the analysis. In the early and maintenance phases, 84% and 76%, respectively, were always adherent, 5% and 5% were non-adherent and 11% and 20% experienced ≥1 treatment interruption. Early non-adherence was independently associated with virological failure (adjusted OR 7.2 [95% CI 1.5, 34.6]), while only treatment interruptions had a significant impact on virological failure during the maintenance phase (adjusted OR 2.1 [95% CI 1.1, 4.4]). Conclusions ART NNRTI-regimens used in sub-Saharan Africa seem to ‘forgive’ deviations from good adherence during the maintenance phase. Optimizing adherence in the early months of treatment remains crucial, especially in a setting of poor health care infrastructure and resources.

Hunting and butchering of wildlife in Central Africa are known risk factors for a variety of human diseases, including HIV/AIDS. Due to the high incidence of human exposure to body fluids of non-human primates, the significant prevalence of simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering associated cross-species transmission of other retroviruses in Central Africa, it is possible that SIV is actively transmitted to humans from primate species other than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus. Additional studies on human populations at risk for non-human primate zoonosis are necessary to determine whether these results are due to viral/host characteristics or are indicative of low SIV prevalence in primate species consumed as bushmeat as compared to other retroviruses in Cameroon.

Background: Rapid scale-up of antiretroviral therapy (ART) in resource-limited settings is accompanied with an increasing risk of HIV drug resistance (HIVDR) which in turn could compromise the performance of national ART rollout programme. In order to sustain the effectiveness of ART in a resource-limited country like Cameroon HIVDR early warning indicators (EWI) may provide relevant corrective measures to support the control and therapeutic management of AIDS. Methods: A retrospective study was conducted in 2010 among 40 ART sites (12 Approved Treatment Centers and 28 Management Units) distributed over the 10 regions of Cameroon. Five standardized EWIs were selected for the evaluation using data from January through December among which: (1) Good ARV prescribing practices: target = 100%; (2) Patient lost to follow-up: target less-than or equal to 20%; (3) Patient retention on first line ART: target greater-than or equal to 70%; (4) On-time drug pick-up: target greater-than or equal to 90%; (5) ARV drug supply continuity: target = 100%. Analysis was performed using a Data Quality Assessment tool following WHO protocol. Results: The number of sites attaining the required performance are: 90% (36/40) for EWI 1 20% (8/40) for EWI 2; 20% (8/40) for EWI 3; 0% (0/37) for EWI 4; and 45% (17/38) for EWI 5. ARV prescribing practices were in conformity with the national guidelines in almost all the sites whereas patient adherence to ART (EWI 2 EWI 3 and EWI 4) was very low. A high rate of patients was lost-to-follow-up and others failing first line ART before 12 months of initiation. Discontinuity in drug supply observed in about half of the sites may negatively impact ARV prescription and patient adherence. These poor ART performances may also be due to low number of trained staff and community disengagement. Conclusions: The poor performance of the national ART programme due to patient non-adherence and drug stock outs requires corrective measures to limit risks of HIVDR emergence in Cameroon.

Hunting and butchering of wildlife in Central Africa are known risk factors for a variety of human diseases, including HIV/AIDS. Due to the high incidence of human exposure to body fluids of non-human primates, the significant prevalence of simian immunodeficiency virus (SIV) in non-human primates, and hunting/butchering associated cross-species transmission of other retroviruses in Central Africa, it is possible that SIV is actively transmitted to humans from primate species other than mangabeys, chimpanzees, and/or gorillas. We evaluated SIV transmission to humans by screening 2,436 individuals that hunt and butcher non-human primates, a population in which simian foamy virus and simian T-lymphotropic virus were previously detected. We identified 23 individuals with high seroreactivity to SIV. Nucleic acid sequences of SIV genes could not be detected, suggesting that SIV infection in humans could occur at a lower frequency than infections with other retroviruses, including simian foamy virus and simian T-lymphotropic virus. Additional studies on human populations at risk for non-human primate zoonosis are necessary to determine whether these results are due to viral/host characteristics or are indicative of low SIV prevalence in primate species consumed as bushmeat as compared to other retroviruses in Cameroon.

Background Scaling up of antiretroviral therapy in low-resource countries is done on the basis of decentralised, integrated HIV care in rural facilities; however, laboratory monitoring is generally unavailable. We aimed to assess the effectiveness and safety of clinical monitoring alone (CLIN) in terms of non-inferiority to laboratory and clinical monitoring (LAB). Methods We did a randomised, open-label, non-inferiority trial in nine rural district hospitals in Cameroon. Eligible participants were adults (>= 18 years) infected with HIV-1 group M (WHO disease stage 3-4) who had not previously received antiretroviral therapy, and were followed-up for 2 years by health-care workers in routine activities. We randomly assigned participants (1:1) to CLIN or LAB (counts of HIV viral load and CD4 cell every 6 months) groups with a computer-generated list. The primary outcome was non-inferiority of CLIN to LAB in terms of increase in CD4 cell count with a non-inferiority margin of 25%. We did all analyses in participants who attended at least one follow-up visit. This trial is registered with ClinicalTrials.gov, number NCT00301561. Findings 238 (93%) of 256 participants assigned to CLIN and 221 (93%) of 237 assigned to LAB were eligible for analysis. CLIN was not non-inferior to LAB; the mean increase in CD4 cell count was 175 cells per mu L (SD 190, 95% CI 151-200) with CLIN and 206 (190,181-231) with LAB (difference 31 [-63 to 2] and non-inferiority margin -52 [-58 to -45]). Furthermore, in the predefined secondary outcome of treatment changes, 13 participants (6%) in the LAB group switched to second-line regimens whereas no participants in the CLIN group did so (p