[Show abstract][Hide abstract] ABSTRACT: Access to antiretroviral treatment (ART) in resource-limited countries has increased significantly but scaling-up ART into semi-rural and rural areas is more recent. Information on treatment outcome in such areas is still very limited notably due to additional difficulties to manage ART in these areas.
387 HIV-1 infected adults (≥18 years) were consecutively enrolled when attending healthcare services for their routine medical visit at 12 or 24 months on first-line ART in five HIV care centers (four semi-rural and one rural). Among them, 102 patients were on first-line ART for 12 ± 2 months (M12) and 285 for 24 ± 2 months (M24). Virological failure was observed in 70 (18.1 %) patients ranging from 13.9 to 31.6 % at M12 and from 8.1 to 22.4 % at M24 across the different sites. For 67/70 patients, sequencing was successful and drug resistance mutations were observed in 65 (97 %). The global prevalence of drug resistance in the study population was thus at least 16.8 % (65/387). Moreover, 32 (8.3 %) and 27 (6.9 %) patients were either on a completely ineffective ART regime or with only a single drug active. Several patients accumulated high numbers of mutations and developed also cross-resistance to abacavir, didanosine or the new NNRTI drugs like etravirine and rilpivirine.
The observations on ART treatment outcome from ART clinics in semi-rural areas are close to previous observations in Lomé, the capital city suggesting that national ART-programme management plays a role in treatment outcome.
Full-text · Article · Dec 2015 · AIDS Research and Therapy
[Show abstract][Hide abstract] ABSTRACT: Information on efficacy of long-term antiretroviral treatment (ART) exposure in resource-limited countries is still scarce. In 767 patients attending routine HIV centers in Togo and receiving first-line ART for more than four years, 42% had viral load greater than 1000?copies/ml and either were on a completely ineffective ART regime or were with only a single drug active. The actual conditions to ensure lifelong ART in resource-limited countries can have dramatic long-term outcomes.
[Show abstract][Hide abstract] ABSTRACT: 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 (<0.02%) for HIV-1 group N and P, and HIV-2 in this country. HIV-1 group O was found at around 0.6% (95% confidence interval: 0.4-0.8%), indicating that the frequency of this virus in Cameroon has remained stable over the last decades. However, we found an extensive high genetic diversity within this HIV-1 group, that resulted from previous steady increase on the effective number of HIV-1 group O infections through time, and the current distribution of the circulating viral strains still does not allow classification as subtypes. The frequency of dual infections with HIV-1 group M and group O was 0.8% (95% confidence interval: 0.6-1.0%), but we found no recombinant forms in co-infected patients. Natural resistance to integrase inhibitors was not identified, although we found several mutations considered as natural polymorphisms. Our study shows that infections with HIV-1 group O can be adequately managed in countries where the virus circulates, but this complex virus still represents a challenge for diagnostics and monitoring strategies.
No preview · Article · Sep 2015 · Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases
[Show abstract][Hide abstract] ABSTRACT: Background:
As part of its policy to shift monitoring of antiretroviral therapy (ART) to primary health care (PHC) workers, the Ministry of Health of the Democratic Republic of Congo (DRC) tested the feasibility of using dried blood spots (DBS) for viral load (VL) quantification and genotypic drug resistance testing in off-site high-throughput laboratories.
DBS samples from adults on ART were collected in 13 decentralized PHC facilities in the Nord-Kivu province and shipped during program quarterly supervision to a reference laboratory 2000 km away, where VL was quantified with a commercial assay (m2000rt, Abbott). A second DBS was sent to a World Health Organization (WHO)-accredited laboratory for repeat VL quantification on a subset of samples with a generic assay (Biocentric) and genotypic drug resistance testing when VL >1000 copies per milliliter.
Constraints arose because of an interruption in national laboratory funding rather than to technical or logistic problems. All samples were assessed by both VL assays to allow ART adjustment. Median DBS turnaround time was 37 days (interquartile range: 9-59). Assays performed unequally with DBS, impacting clinical decisions, quality assurance, and overall cost-effectiveness. Based on m2000rt or generic assay, 31.3% of patients were on virological failure (VF) and 14.8% presented resistance mutations versus 50.3% and 15.4%, respectively.
This study confirms that current technologies involving DBS make virological monitoring of ART possible at PHC level, including in challenging environments, provided organizational issues are addressed. Adequate core funding of HIV laboratories and adapted choice of VL assays require urgent attention to control resistance to ART as coverage expands.
[Show abstract][Hide abstract] ABSTRACT: Ebola virus disease is a complex zoonosis and each outbreak is the result of independent zoonotic events. In certain outbreaks, even more than one cross-species transmission was involved. Today it is believed that human infection with Ebola Virus (EBV) can result from exposure to infected blood during hunting and butchering of infected animals for food or via contact with fruit contaminated with EBV by faeces or saliva from bats. Viral RNA from Zaire EBV has been identified in three fruit bat species from Gabon (Epomops franqueti, Hypsignathus monstrosus, and Myonycteris torquata). Other studies across Africa (Ghana, Gabon, Congo and Zambia) documented EBV antibodies in additional fruit and insect bat species (Eidolon helvum, Epomophorus gambianus, Micropteropus pusillus, Mops condylurus, Rousettus aegyptiacus, and Rousettus leschenaultii). Bats are at the origin of two EBV outbreaks; as bushmeat in the 2008 EBV outbreak in Luebo (DRC) and the index case (a 2-year-old boy in Meliandou) from the actual epidemic in Guinea, may have been infected by playing in a hollow tree housing a colony of insectivorous free-tailed bats (Mops condylurus). However, at least 8 of the 25 outbreaks have been related to contact with NHP (non-human primates), mainly apes. For the other EBV outbreaks, the zoonotic source is unknown. Since significant mortality related to EBV has been reported in wild gorillas (Gorilla gorilla) and chimpanzees (Pan troglodytes) in Gabon and Congo and also in chimpanzees from the Tai forest in Ivory Coast, apes are likely dead-end hosts for the virus and not reservoir species, but they play a role as amplifying host. EBV antibodies have also been observed in several wild-captured but captive non-human primate (NHP) species (chimpanzees, gorillas, mandrills, drills, baboons and Cercopithecus species) from Cameroon and Gabon, suggesting that EBV could be more widespread among NHP and that non-lethal or asymptomatic infections could occur in certain NHPs. Today, many questions still remain on the animal reservoir: how is EBV maintained and transmitted among bats and across the African continent, for example the Zaire EBV strain identified in the actual outbreak in West Africa diverged from Central African strains 10 years ago; how is the virus transmitted between different animal species; what is the role of reservoir and/or amplifying hosts in human outbreaks; to what extend are other Ebola viruses (Tai, Bundinguyo, Sudan, Reston,) present in animals; to what extend other unrecognized outbreaks occurred in humans.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
[Show abstract][Hide abstract] ABSTRACT: HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples from western lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids. Despite testing wild troops throughout southern Cameroon (n = 14), northern Gabon (n = 16), the Democratic Republic of Congo (n = 2), and Uganda (n = 1), SIVgor was identified at only four sites in southern Cameroon, with prevalences ranging from 0.8–22%. Amplification of partial and full-length SIVgor sequences revealed extensive genetic diversity, but all SIVgor strains were derived from a single lineage within the chimpanzee SIV (SIVcpz) radiation. Two fully sequenced gorilla viruses from southwestern Cameroon were very closely related to, and likely represent the source population of, HIV-1 group P. Most of the genome of a third SIVgor strain, from central Cameroon, was very closely related to HIV-1 group O, again pointing to gorillas as the immediate source. Functional analyses identified the cytidine deaminase APOBEC3G as a barrier for chimpanzee-to-gorilla, but not gorilla-to-human, virus transmission. These data indicate that HIV-1 group O, which spreads epidemically in west central Africa and is estimated to have infected around 100,000 people, originated by cross-species transmission from western lowland gorillas.
Full-text · Article · Mar 2015 · Proceedings of the National Academy of Sciences
[Show abstract][Hide abstract] ABSTRACT: Simian immunodeficiency virus (SIV) infects many primate species. Chimpanzees (Pan troglodytes) can develop an immune disease similar to human acquired immunodeficiency syndrome (AIDS). Immunosuppressed patients often suffer from opportunistic diseases such as microsporidiosis and cryptosporidiosis. We report on the occurrence of infections with microsporidia and Cryptosporidium spp. in wild-living chimpanzees, gorillas (Gorilla gorilla gorilla), bonobos (Pan paniscus), and four monkey species from the Cercopithecinae subfamily (Cercocebus agilis, Cercopithecus cephus, Cercopithecus nictitans, and Lophocebus albigena) and assess whether these infections may be good indicators of SIV-related immunosuppression. We analyzed 399 fecal samples collected in Cameroon and Democratic Republic of Congo for the presence of cross-reactive HIV antibodies using a line immunoassay (INNO-LIA®). We amplified via polymerase chain reaction (PCR) a 200–500 bp DNA fragment for the genus Encephalitozoon and the genus Enterocytozoon respectively (microsporidia), and an 820 bp DNA fragment of various Cryptosporidium species. Twenty-nine percent (45/155) of the chimpanzees samples analyzed were SIV+, whereas samples from the other primate species were SIV–. Phylogenetic analyses showed that 11 fecal samples [one SIV+, four SIV– chimpanzees, three gorillas, a bonobo, an agile mangabey (Cercocebus agilis), and a moustached monkey (Cercopithecus cephus)] are infected with microsporidia. DNA sequences of amplicons derived from eight fecal samples clustered together with Encephalitozoon hellem and three branched close to E. intestinalis. We also amplified Cryptosporidium spp. in two SIV+ chimpanzee samples and in two gorilla samples. We found no significant association between SIV infection status in chimpanzees and the presence of microsporidia or Cryptosporidium, suggesting that detection of microsporidia and Cryptosporidium is not a reliable marker for immunosuppressive status in SIV-infected primates.
Full-text · Article · Feb 2015 · International Journal of Primatology
[Show abstract][Hide abstract] ABSTRACT: Background:
Chimpanzees (Pan troglodytes) can be divided into four subspecies. Substantial phylogenetic evidence suggests that these subspecies can be grouped into two distinct lineages: a western African group that includes P. t. verus and P. t. ellioti and a central/eastern African group that includes P. t. troglodytes and P. t. schweinfurthii. The geographic division of these two lineages occurs in Cameroon, where the rages of P. t. ellioti and P. t. troglodytes appear to converge at the Sanaga River. Remarkably, few population genetic studies have included wild chimpanzees from this region.
We analyzed microsatellite genotypes of 187 wild, unrelated chimpanzees, and mitochondrial control region sequencing data from 604 chimpanzees. We found that chimpanzees in Cameroon and eastern Nigeria comprise at least two, and likely three populations. Both the mtDNA and microsatellite data suggest that there is a primary separation of P. t. troglodytes in southern Cameroon from P. t. ellioti north and west of the Sanaga River. These two populations split ~200-250 thousand years ago (kya), but have exchanged one migrant per generation since separating. In addition, P. t. ellioti consists of two populations that split from one another ~4 kya. One population is located in the rainforests of western Cameroon and eastern Nigeria, whereas the second population appears to be confined to a savannah-woodland mosaic in central Cameroon.
Our findings suggest that there are as many as three genetically distinct populations of chimpanzees in Cameroon and eastern Nigeria. P. t. troglodytes in southern Cameroon comprises one population that is separated from two populations of P. t. ellioti in western and central Cameroon, respectively. P. t. ellioti and P. t. troglodytes appear to be characterized by a pattern of isolation-with-migration, and thus, we propose that neutral processes alone can not explain the differentiation of P. t. ellioti and P. t. troglodytes.
Full-text · Article · Jan 2015 · BMC Evolutionary Biology
[Show abstract][Hide abstract] ABSTRACT: Simian immunodeficiency viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in faecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1-infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority.
[Show abstract][Hide abstract] ABSTRACT: Over 40 species of African non-human primates are naturally infected with species-specific simian immunodeficiency viruses (SIVs). Prevalence of SIV infection in these species is variable, ranging from <1% to 80-90%. SIVs coexisted with their host species for a long time and as a result, SIVs are highly adapted to their hosts. With the exception of chimpanzees, SIV infection generally does not progress to AIDS in natural hosts. Comparing and contrasting the natural history of SIV infection in natural hosts to that of pathogenic SIV/HIV infections will lead us toward a better understanding of the basis of virulence versus avirulence and permit us to identify new therapeutic strategies to mitigate or control the deleterious consequences of HIV infection.
[Show abstract][Hide abstract] ABSTRACT: Simian Immunodeficiency Viruses (SIVs) have been discovered in over 45 primate species; however, the pathogenic potential of most SIV strains remains unknown due to difficulties inherent in observing wild populations. Because those SIV infections that are pathogenic have been shown to induce changes in the host's gut microbiome, monitoring the microbiota present in fecal samples can provide a noninvasive means for studying the effects of SIV infection on the health of wild-living primates. Here, we examine the effects of SIVgor, a close relative of SIVcpz of chimpanzees and HIV-1 of humans, on the gut bacterial communities residing within wild gorillas, revealing that gorilla gut microbiomes are exceptionally robust to SIV infection. In contrast to the microbiomes of HIV-1 infected humans and SIVcpz-infected chimpanzees, SIVgor-infected gorilla microbiomes exhibit neither rises in the frequencies of opportunistic pathogens nor elevated rates of microbial turnover within individual hosts. Regardless of SIV infection status, gorilla microbiomes assort into enterotypes, one of which is compositionally analogous to those identified in humans and chimpanzees. The other gorilla enterotype appears specialized for a leaf-based diet and is enriched in environmentally derived bacterial genera. We hypothesize that the acquisition of this gorilla-specific enterotype was enabled by lowered immune-system control over the composition of the microbiome. Our results indicate differences between the pathology of SIVgor and SIVcpz/HIV-1 infections, demonstrating the utility of investigating host microbial ecology as a means for studying disease in wild primates of high conservation priority. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
No preview · Article · Dec 2014 · Molecular Ecology
[Show abstract][Hide abstract] ABSTRACT: Access to antiretroviral treatment (ART) becomes more and more effective in resource-limited settings (RLS). However, this global effort would be even more profitable if the access to laboratory services especially in decentralized settings was strengthened. We report the virological outcome and HIV-1 drug resistance in three West African countries using dried blood spots (DBS) samples.
We included HIV-1-infected adults on ART ≥6 months and followed up in capital cities and decentralized sites in Senegal, Mali and Guinea-Conakry. Patients were consecutively enrolled and DBS were collected in field conditions and kept at ambient temperature before transfer to the reference laboratory. Viral load (VL) was quantified using the NucliSENS EasyQ HIV-1 v1.2. Genotyping of HIV-1 pol gene was performed using in-house protocol.
Of the 407 participants, 119, 152 and 136 were from Senegal, Mali and Guinea-Conakry, respectively. The median treatment duration was 36 months [IQR: 6-136]. Virological failure (VF) (VL≥3log10 copies/mL) was observed in 26% (95% confidence interval (CI), 18-35; n=31), 11% (95% CI, 6-17; n=16) and 24% (95% CI, 17-32; n=33) of patients in Senegal, Mali and Guinea-Conakry, respectively (p=0.001). Of samples presenting VL≥3log10 copies/mL (n=80), 70 were successfully genotyped. At least one drug resistance mutation (DRM) was detected in the following proportions: 70% (95% CI, 50-86; n=19), 93% (95% CI, 68-100; n=14) and 68% (95% CI, 48-84; n=19) in Senegal, Mali and Guinea-Conakry, respectively (p=0.22). Twenty-six per cent (26%; 95% CI, 16-38; n=18) of patients in VF harboured wild-type viruses, which is likely indicative of weak adherence. Phylogenetic analysis showed the predominance of CRF02_AG subtype (73%; 95% CI, 61-83; n=51).
We describe the ART outcome in capital and rural settings of Senegal, Mali and Guinea-Conakry. Our results in all of the three countries highlight the need to reinforce the ART adherence in order to minimize the occurrence of drug resistance. In addition, these findings provide additional evidence that the use of DBS as a sampling support could assist virological monitoring of patients on ART in remote areas.
Full-text · Article · Dec 2014 · Journal of the International AIDS Society
[Show abstract][Hide abstract] ABSTRACT: Wild apes are considered to be the most serious reservoir and source of zoonoses. However, little data are available about the gut microbiota and pathogenic bacteria in gorillas. For this propose, a total of 48 fecal samples obtained from 21 Gorilla gorilla gorilla individuals (as revealed via microsatellite analysis) were screened for human bacterial pathogens using culturomics and molecular techniques. By applying culturomics to one index gorilla and using specific media supplemented by plants, we tested 12,800 colonies and identified 147 different bacterial species, including 5 new species. Many opportunistic pathogens were isolated, including 8 frequently associated with human diseases; Mycobacterium bolletii, Proteus mirabilis, Acinetobacter baumannii, Klebsiella pneumoniae, Serratia marcescens, Escherichia coli, Staphylococcus aureus and Clostridium botulinum. The genus Treponema accounted for 27.4% of the total reads identified at the genus level via 454 pyrosequencing. Using specific real-time PCR on 48 gorilla fecal samples, in addition to classical human pathogens, we also observed the fastidious bacteria Bartonella spp. Borrelia spp., Coxiella burnetii and Tropheryma whipplei in the gorilla population. We estimated that the prevalence of these pathogens vary between 4.76% and 85.7%. Therefore, gorillas share many bacterial pathogens with humans suggesting that they could be a reservoir for their emergence.
Full-text · Article · Nov 2014 · Scientific Reports