Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Prevalence of HIV drug resistance among adolescents receiving ART in Cameroon with low- or high-level viraemia.

OBJECTIVES: To characterize HIV drug resistance (HIVDR) below and above the WHO threshold of 1000 copies/mL, considered for the definition of HIV ART failure in resource-limited settings. METHODS: From a cohort of 280 adolescents (aged 10-19 years) receiving ART for at least 6 months, genotypic resistance testing (GRT) was attempted for two groups of participants: participants with low-level viraemia [LLV; viral load (VL) 200-999 copies/mL] and those in virological failure (VF; confirmed VL ≥1000 copies/mL) using an in-house method. The Stanford HIValg Program was used to identify relevant HIVDR mutations and predict the efficacy of the newly introduced tenofovir-lamivudine-dolutegravir combination. RESULTS: GRT was successfully performed in 54/58 (93.1%) eligible participants, of which 28/31 (90.3%) were in VF and 26/27 (96.3%) had LLV. A high level of resistance was found both in adolescents with LLV and those in VF, with respectively 84.6% (22/26) and 75.0% (21/28) of participants harbouring at least one HIVDR mutation. NRTIs and NNRTIs were the most affected drug classes in both population groups. In contrast, PIs were not significantly affected and dolutegravir was expected to be active for all participants tested. However, for the newly introduced dolutegravir-based combination, functional monotherapy (dolutegravir only) was potentially possible for 22.7% (5/22) of the participants with LLV. CONCLUSIONS: Our findings show that the 1000 copies/mL threshold is not an indicator of virological success and we call for a revision of the current WHO definition of VF in resource-limited countries.

Viral load suppression in HIV-infected adolescents in cameroon: towards achieving the UNAIDS 95% viral suppression target.

BACKGROUND: Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. METHODS: A cross-sectional study was carried out in 2021 among adolescents (aged 10-19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients' medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. RESULTS: Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0-18.0) years and the median duration on ART was 9.8 (IQR: 5.1-12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. CONCLUSION: The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. TRIAL REGISTRATION: 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).

High rate of virological failure and HIV drug resistance in semi-rural Gabon and implications for dolutegravir-based regimen efficacy.

BACKGROUND: The projected UNAIDS goal of ending AIDS by 2030 requires significant global efforts to improve current and future ART strategies. In this study, we assessed viral load (VL) suppression and acquired drug resistance, as well as future efficacy of dolutegravir-based combinations for patients living in semi-rural regions of Gabon. METHODS: Eligible study participants were adults receiving ART and recruited between 2018 and 2019 in Franceville, Gabon. VL testing was conducted to assess VL suppression and HIV drug resistance (HIVDR) testing was performed to identify resistance mutations and assess their impact on ongoing and future ART regimens. RESULTS: We recruited 219 participants overall. The median time on ART was 27 months and 216/219 participants were on first-line ART. VL suppression (VL < 1000 copies/mL) was 57.1% (95% CI 50.5-63.8) overall; 59.4% (51.4-67.5) and 52.2% (40.3-64.2) for women and men, respectively. The overall prevalence of HIVDR was 21.9% among the study population and 67.2% among those who failed ART. Presence of both NRTI and NNRTI mutations was found in 84.6% of sequences with drug resistance mutations, and full activity of a dolutegravir-based first-line regimen including tenofovir disoproxil fumarate/lamivudine/dolutegravir was expected only for 5/39 patients with a resistant virus. CONCLUSIONS: This study shows a very low rate of VL suppression in a semi-rural context in Africa. Moreover, the high burden of HIVDR has affected both current and newly recommended ART strategies. Better management of ART in resource-limited settings is still a challenging ambition.

Prevalence of pretreatment HIV drug resistance in West African and Southeast Asian countries.

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.

Prevalence of pretreatment HIV drug resistance in Cameroon following a nationally representative WHO survey.

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 Yaoundé, 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.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

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 positions­a proxy for recent infection­yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs­K101E, K103N, Y181C, and G190A­accounted 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.

Extraordinary heterogeneity of virological outcomes in patients receiving highly antiretroviral therapy and monitored with the World Health Organization public health approach in sub-saharan Africa and southeast Asia.

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 genotyped 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/µL). 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.

Field evaluation of dried blood spots for routine HIV-1 viral load and drug resistance monitoring in patients receiving antiretroviral therapy in Africa and Asia.

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at -20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored.

Declining trends in early warning indicators for HIV drug resistance in Cameroon from 2008-2010: lessons and challenges for low-resource settings.

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: EWI(1) (100% to 70%); EWI(2) (40% to 20%); EWI(3) (70% to 0%); EWI(4) (0% throughout); EWI(5) (90% to 40%). Thus, prescribing practices (EWI(1)) were in conformity with national guidelines, while patient adherence (EWI(2), EWI(3), and EWI(4)) and drug supply (EWI(5)) 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.

Burden of hepatitis B virus infection in pregnant women attending antenatal clinics in the southern Gabon.

Objectives: Hepatitis B virus (HBV) infection remains a public health threat in middle- and low-income countries, where mother-to-child transmission plays an important role. The aim of this study was to assess the burden of this infection among pregnant women in southern Gabon and the risk of vertical transmission. Methods: The study was a prospective investigation conducted from April 2021 to January 2022. Study participants were pregnant women aged 18 and over attending antenatal clinics in Franceville. Blood samples were collected to test for HBV surface antigen, anti-hepatitis B core, hepatitis B e antigen, and anti-hepatitis B e markers and to assess HBV infection. Results: We recruited 901 women with a median age of 26 years (interquartile range: 21-32). Overall prevalence of infection was 3.9% (confidence interval: 2.7-5.4%). 418/901 or 46.4% were anti-hepatitis B core positive. Among HBV surface antigen-positive women, 1/35 were hepatitis B e antigen-positive with a viral load >200,000 IU/ml. Over 64% of participants had no information about HBV infection, and none knew that the virus could be transmitted from mother to child. Conclusions: This study reveals a low HBV prevalence in pregnant women in Gabon and a low risk of vertical transmission of the virus. However, the rate of exposure of the population to the virus remains high and calls for improving actions and interventions for potential elimination goals.

Prevalence of SARS-CoV-2 antibodies in the Republic of Congo in mid-2021.

Objectives: To estimate the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in the general population in the Republic of Congo. Methods: In this cross-sectional study, conducted from June to July 2021, participants were recruited from the general population in three districts in the Republic of Congo. Eligible participants were tested for anti-SARS-CoV-2 antibodies using a rapid diagnostic assay. Results: Overall, 31.8% [95% confidence interval (CI) 29.5-34.0] of the 1669 participants tested positive for anti-SARS-CoV-2 antibodies. Higher prevalence was observed in the rural region (37.3%, 95% CI 31.0-44.1%) than the urban region (30.9%, 95% CI 28.5-33.3); however, the difference was not significant. The risk of testing positive for anti-SARS-CoV-2 antibodies increased significantly with age, ranging from 22.5% (95% CI 18.1-27.5) in 15-24 year olds to 47.9% (95% CI 39.3-56.5) in 55-64 year olds. Conclusions: The antibody levels observed in this survey correlate with a moderate rate of virus circulation, which correlates with the low number of confirmed cases of coronavirus disease 2019 in the Republic of Congo.

Trend of expansion of SARS-CoV-2 infection and COVID-19 burden in Gabon (Central Africa) in mid-2021, based on a serological survey.

Objective: To estimate the seroprevalence of anti-SARS-CoV-2 antibodies in the general population in Gabon, Central Africa. Methods: From May to July 2021, a cross-sectional study involving participants recruited in the general population in three districts in Gabon was conducted. Eligible participants who provided written informed consent were tested for anti-SARS-CoV-2 antibodies using a simple rapid diagnostic assay. Results: Overall, 1609 participants were recruited, 1361 (84.6%) from urban sites and 248 (15.4%) from a rural area. The estimated overall seroprevalence was 13.1% (95% CI 11.4-14.8%). The risk of seropositivity increased with age, and the prevalence in the different age groups ranged from 12.9% (8.0-19.4%) in those aged 15-24 years to 23.3% (14.2-34.6%) in those ≥ 65 years old. A higher prevalence was found in the rural population (17.3%; 12.8-22.6%) compared with urban regions (12.3%; 10.6-14.1%). Being a woman was also associated with higher risk of infection (p < 0.001). Conclusions: This seroprevalence survey revealed a moderate seroprevalence in Gabon, illustrating a relatively low rate of circulation of the virus in the country and correlating with low numbers of confirmed cases and deaths reported to date.

Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms.

BACKGROUND: Data on the evolution of natural SIV infection in chimpanzees (SIVcpz) and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (Pan troglodytes schweinfurthii), and no data exist for Central chimpanzees (Pan troglodytes troglodytes), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a P.t.troglodytes chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection. RESULTS: A male chimpanzee (Cam155), 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm³ in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm³ in 2004 vs 5,000 cells/mm³ in 2009), a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg) and frequent periods of infections with diverse pathogens.DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpzPtt-Cam155 genomes. SIVcpzPtt-Cam155 was phylogenetically related to other SIVcpzPtt from Cameroon (SIVcpzPtt-Cam13) and Gabon (SIVcpzPtt-Gab1). Ten molecular clones 5 years apart, spanning the V1V4 gp120 env region (1,100 bp), were obtained. Analyses of the env region showed positive selection (dN-dS >0), intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p < 0.0001). CONCLUSIONS: Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected P.t.troglodytes chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in P.t.schweinfurthii. Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.

High failure rate of the ViroSeq HIV-1 genotyping system for drug resistance testing in Cameroon, a country with broad HIV-1 genetic diversity.

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.

Genetic diversity of simian lentivirus in wild De Brazza's monkeys (Cercopithecus neglectus) in Equatorial Africa.

De Brazza's monkeys (Cercopithecus neglectus) are non-human primates (NHP) living in Equatorial Africa from South Cameroon through the Congo-Basin to Uganda. As most of the NHP living in sub-Saharan Africa, they are naturally infected with their own simian lentivirus, SIVdeb. Previous studies confirmed this infection for De Brazza's from East Cameroon and Uganda. In this report, we studied the genetic diversity of SIVdeb in De Brazza's monkeys from different geographical areas in South Cameroon and from the Democratic Republic of Congo (DRC). SIVdeb strains from east, central and western equatorial Africa form a species-specific monophyletic lineage. Phylogeographic clustering was observed among SIVdeb strains from Cameroon, the DRC and Uganda, but also among primates from distinct areas in Cameroon. These observations suggest a longstanding virus-host co-evolution. SIVdeb prevalence is high in wild De Brazza's populations and thus represents a current risk for humans exposed to these primates in central Africa.

WHO clinical criteria-based initiation of antiretroviral therapy: lessons from rural district hospitals in Cameroon with regard to 2009 revised WHO recommendations.

OBJECTIVE: To assess the proportion of patients infected with HIV with a CD4 count above 350 cells/mm(3) among those classified at WHO clinical stage 3 or 4 who initiated antiretroviral therapy in rural district hospitals in Cameroon to assess the 2009 revised WHO recommendations. METHODS: Cross-sectional study in nine rural district hospitals where the treatment initiation is based on the WHO clinical criteria. The proportion of patients who were classified at stage 3 or 4 and who had a CD4 count >350 cells/mm(3) was assessed. RESULTS: Of 458 patients included in 2006-2008 (women 70.5%; median age 37.0 years), 337 (73.6%) were classified at WHO clinical stage 3 and 121 (26.4%) at stage 4. Overall, 108 patients (23.6%) had a CD4 count >350 cells/mm(3). Of them, 94 patients (20.5%) were classified at WHO clinical stage 3, and 14 (3.1%) were classified at WHO clinical stage 4. CONCLUSION: The WHO clinical stages 3 and 4 were poorly correlated with the 'gold standard' of CD4 cell count. This study highlights the need to promote CD4 testing for assessing the patient eligibility.

Tenofovir resistance in early and long-term treated patients on first-line antiretroviral therapy in eight low-income and middle-income countries.

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.