Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

OBJECTIVE: Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. METHODS: Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. RESULTS: Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. CONCLUSIONS: This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support

Simian immunodeficiency virus infection in wild-caught chimpanzees from Cameroon

Simian immunodeficiency viruses (SIVcpz) infecting chimpanzees (Pan troglodytes) in west central Africa are the closest relatives to all major variants of human immunodeficiency virus type 1 ([HIV-1]; groups M, N and O), and have thus been implicated as the source of the human infections; however, information concerning the prevalence, geographic distribution, and subspecies association of SIVcpz still remains limited. In this study, we tested 71 wild-caught chimpanzees from Cameroon for evidence of SIVcpz infection. Thirty-nine of these were of the central subspecies (Pan troglodytes troglodytes), and 32 were of the Nigerian subspecies (Pan troglodytes vellerosus), as determined by mitochondrial DNA analysis. Serological analysis determined that one P. t. troglodytes ape (CAM13) harbored serum antibodies that cross-reacted strongly with HIV-1 antigens; all other apes were seronegative. To characterize the newly identified virus, 14 partially overlapping viral fragments were amplified from fecal virion RNA and concatenated to yield a complete SIVcpz genome (9,284 bp). Phylogenetic analyses revealed that SIVcpzCAM13 fell well within the radiation of the SIVcpzPtt group of viruses, as part of a clade including all other SIVcpzPtt strains as well as HIV-1 groups M and N. However, SIVcpzCAM13 clustered most closely with SIVcpzGAB1 from Gabon rather than with SIVcpzCAM3 and SIVcpzCAM5 from Cameroon, indicating the existence of divergent SIVcpzPtt lineages within the same geographic region. These data, together with evidence of recombination among ancestral SIVcpzPtt lineages, indicate long-standing endemic infection of central chimpanzees and reaffirm a west central African origin of HIV-1. Whether P. t. vellerosus apes are naturally infected with SIVcpz requires further study

Complete genome analysis of one of the earliest SIVcpzPtt strains from Gabon (SIVcpzGAB2)

Chimpanzees in west central Africa (Pan troglodytes troglodytes) are known to harbor simian immunodeficiency viruses (SIVcpzPtt) that represent the closest relatives of human immunodeficiency virus type 1 (HIV-1); however, the number of SIVcpzPtt strains that have been fully characterized is still limited. Here, we report the complete nucleotide sequence of SIVcpzGAB2, a virus originally identified in 1989 in a chimpanzee (P. t. troglodytes) from Gabon. Analysis of this sequence reveals that SIVcpzGAB2 is a member of the SIVcpzPtt group of viruses, but that it differs from other SIVcpzPtt strains by exhibiting a highly divergent Env V3 loop with an unusual crown (NLSPGTT) containing a canonical N-linked glycosylation site, an unpaired cysteine residue in Env V4, and two late (L) domain motifs (PTAP and YPSL) in Gag p6. Moreover, phylogenetic analyses indicate evidence of recombination during the early divergence of SIVcpzPtt strains; in particular, part of the pol gene sequence of SIVcpzGAB2 appears to be derived from a previously unidentified SIVcpz lineage ancestral to HIV-1 group O. These data indicate extensive diversity among naturally occurring SIVcpzPtt strains and provide new insight into the origin of HIV-1 group O

Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy

Full-length genome sequence of a simian immunodeficiency virus (SIV) infecting a captive agile mangabey (Cercocebus agilis) is closely related to SIVrcm infecting wild red-capped mangabeys (Cercocebus torquatus) in Cameroon

Simian immunodeficiency viruses (SIVs) are lentiviruses that infect an extensive number of wild African primate species. Here we describe for the first time SIV infection in a captive agile mangabey (Cercocebus agilis) from Cameroon. Phylogenetic analysis of the full-length genome sequence of SIVagi-00CM312 showed that this novel virus fell into the SIVrcm lineage and was most closely related to a newly characterized SIVrcm strain (SIVrcm-02CM8081) from a wild-caught red-capped mangabey (Cercocebus torquatus) from Cameroon. In contrast to red-capped mangabeys, no 24 bp deletion in CCR5 has been observed in the agile mangabey. Further studies on wild agile mangabeys are needed to determine whether agile and red-capped mangabeys are naturally infected with the same SIV lineage, or whether this agile mangabey became infected with an SIVrcm strain in captivity. However, our study shows that agile mangabeys are susceptible to SIV infection

HIV Viral Load Testing in Laos

The number of people living with HIV/AIDS in the People’s Democratic Republic of Laos (also known as Laos PDR) is estimated at 13,600 and the number of people in need of antiretroviral therapy at 8,000. Today, around 3,200 HIV infected individuals receive treatment in seven centres throughout the country. Until recently, antiretroviral treated patients were followed-up only on the basis of clinical and immunological criteria. In 2009 the Centre d'Infectiologie Christophe Mérieux in Laos PDR (CICML) signed a collaboration agreement with the national Centre of HIV/AIDS/STI (CHAS) for the implementation of HIV viral load testing (VLT) in the country, leading to the technological transfer of the ANRS generic assay (HIV Generic charge virale, Biocentric, Bandol, France). The introduction of HIV VLT has been accompanied through national HIV workshops every 6 months. From June 2009 to December 2011, HIV viral load has been measured in 1,782 antiretoviral-treated patients. Of these, 97% were on reverse-transcriptase inhibitor -based 1st line regimen. HIV viral load was undetectable (<250 copies/ml) for 1,491 out of 1,782 (84%) antiretroviral-treated patients. Four months after adherence strengthening, HIV viral load became undetectable for 179/247 patients (72.5%) while 68/247 patients (27.5%) remained viremic (median viral load: 4.1 Log10). This report demonstrates the feasibility of setting up an affordable HIV viral load generic test at a national level in Laos PDR. Interestingly, only 16% of antiretroviral-treated patients presented with detectable VL at their first viral load measurement. Importantly, almost two thirds of them have controlled their viral load after strengthening their adherence to treatment.La République démocratique populaire du Laos compterait 13 600 personnes atteintes du VIH/SIDA dont 8000 auraient besoin d’un traitement antirétroviral. Aujourd’hui, environ 3200 individus infectés par le VIH reçoivent un traitement dans sept centres répartis dans tout le pays. Jusqu’à récemment, le suivi des patients traités par antirétroviraux se faisait uniquement sur la base de critères cliniques et immunologiques. En 2009, le Centre d'Infectiologie Christophe Mérieux du Laos (CICML) a signé un accord de collaboration avec le Programme national SIDA du Laos (CHAS) pour la mise en œuvre de tests de détection de la charge virale de VIH (VLT) dans le pays, qui permettra le transfert technologique de la technique générique ANRS (HIV Generic charge virale, Biocentric, Bandol, France). L’introduction du VLT appliqué au VIH s’est faite au travers d’ateliers nationaux sur le VIH tous les 6 mois. De juin 2009 à décembre 2011, la charge virale de VIH a été mesurée chez 1782 patients traités par antirétroviraux. Parmi eux, 97 % prenaient un traitement de première intention à base d’inhibiteur de la transcriptase inverse. La charge virale de VIH était indétectable (<250 copies/ml) chez 1491 des 1782 (84 %) patients traités par antirétroviraux. Quatre mois après renforcement de l’administration du traitement, la charge virale de VIH est devenue indétectable chez 179/247 patients (72,5 %) tandis que 68/247 patients (27,5 %) sont demeurés virémiques (charge virale médiane : 4,1 Log10). Cet article montre la faisabilité de la mise en place d’un test de détection générique de la charge virale de VIH abordable au niveau national au Laos. Il est intéressant de noter que seuls 16 % des patients traités par antirétroviraux ont présenté une charge virale détectable lors de la première mesure. En outre, près des deux-tiers d’entre eux ont pu maîtriser leur charge virale par une meilleure administration du traitement.El número de personas que padecen VIH/SIDA en la República Democrática Popular de Laos (también conocida como RDP Lao) se estima en 13.600, y el número de personas que necesitan un tratamiento antirretroviral es de 8.000. En la actualidad, cerca de 3.200 personas infectadas por el VIH reciben tratamiento en siete centros repartidos por todo el país. Hasta hace poco, el seguimiento de los pacientes tratados con fármacos antirretrovirales dependía exclusivamente de criterios clínicos e inmunológicos. En el 2009, el Centro de Infectología Christophe Mérieux de PDR Lao (CICML) suscribió un acuerdo de colaboración con el Centro Nacional de VIH/SIDA/ITS (CHAS) para la implantación del estudio de la carga viral del VIH (VLT, por sus siglas en inglés) en el país, lo que comportaría la transferencia de la tecnología del ensayo genérico ANRS (carga viral genérica del VIH, Biocentric, Bandol, Francia). La introducción del estudio de la carga viral del VIH se ha visto respaldada por la realización de varios talleres nacionales sobre el VIH cada 6 meses. Desde junio de 2009 a diciembre de 2011 se ha medido la carga vírica del VIH de 1.782 pacientes tratados con antirretrovirales. El 97 % de ellos seguía un régimen antirretroviral de primera línea basado en inhibidores de la transcriptasa inversa. No se detectó carga viral del VIH (<250 copias/ml) en 1.491 de 1.782 (84 %) de los pacientes tratados con antirretrovirales. Cuatro meses después del fortalecimiento de la adherencia, no se detectó carga viral del VIH en 179 de 247 pacientes (72,5 %) mientras que 68 de 247 pacientes (27,5 %) seguían siendo virémicos (carga viral media: 4,1 Log10). Este informe demuestra la viabilidad de elaborar un estudio genérico de la carga viral del VIH económico a nivel nacional en la RDP Lao). Cabe destacar que solamente el 16 % de los pacientes tratados con antirretrovirales presentaron una carga viral detectable en su primera medición de la carga viral. Es significativo que casi dos terceras partes de ellos hayan conseguido controlar su carga viral después de fortalecer su adherencia al tratamiento

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

<p>Abstract</p> <p>Background</p> <p>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 (<it>Pan troglodytes schweinfurthii</it>), and no data exist for Central chimpanzees (<it>Pan troglodytes troglodytes</it>), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a <it>P.t.troglodytes </it>chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection.</p> <p>Results</p> <p>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/mm³in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm³in 2004 vs 5,000 cells/mm³in 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.</p> <p>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 SIVcpz<it>Ptt</it>-Cam155 genomes. SIVcpz<it>Ptt</it>-Cam155 was phylogenetically related to other SIVcpz<it>Ptt </it>from Cameroon (SIVcpz<it>Ptt</it>-Cam13) and Gabon (SIVcpz<it>Ptt</it>-Gab1). Ten molecular clones 5 years apart, spanning the V1V4 gp120 <it>env </it>region (1,100 bp), were obtained. Analyses of the <it>env </it>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).</p> <p>Conclusions</p> <p>Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected <it>P.t.troglodytes </it>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 <it>P.t.schweinfurthii</it>. 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.</p

Tracing the origins of rescued chimpanzees reveals widespread chimpanzee hunting in Cameroon

<p>Abstract</p> <p>Background</p> <p>While wild chimpanzees are experiencing drastic population declines, their numbers at African rescue and rehabilitation projects are growing rapidly. Chimpanzees follow complex routes to these refuges; and their geographic origins are often unclear. Identifying areas where hunting occurs can help law enforcement authorities focus scarce resources for wildlife protection planning. Efficiently focusing these resources is particularly important in Cameroon because this country is a key transportation waypoint for international wildlife crime syndicates. Furthermore, Cameroon is home to two chimpanzee subspecies, which makes ascertaining the origins of these chimpanzees important for reintroduction planning and for scientific investigations involving these chimpanzees.</p> <p>Results</p> <p>We estimated geographic origins of 46 chimpanzees from the Limbe Wildlife Centre (LWC) in Cameroon. Using Bayesian approximation methods, we determined their origins using mtDNA sequences and microsatellite (STRP) genotypes compared to a spatial map of georeferenced chimpanzee samples from 10 locations spanning Cameroon and Nigeria. The LWC chimpanzees come from multiple regions of Cameroon or forested areas straddling the Cameroon-Nigeria border. The LWC chimpanzees were partitioned further as originating from one of three biogeographically important zones occurring in Cameroon, but we were unable to refine these origin estimates to more specific areas within these three zones.</p> <p>Conclusions</p> <p>Our findings suggest that chimpanzee hunting is widespread across Cameroon. Live animal smuggling appears to occur locally within Cameroon, despite the existence of local wildlife cartels that operate internationally. This pattern varies from the illegal wildlife trade patterns observed in other commercially valuable species, such as elephants, where specific populations are targeted for exploitation. A broader sample of rescued chimpanzees compared against a more comprehensive grid of georeferenced samples may reveal 'hotspots' of chimpanzee hunting and live animal transport routes in Cameroon. These results illustrate also that clarifying the origins of refuge chimpanzees is an important tool for designing reintroduction programs. Finally, chimpanzees at refuges are frequently used in scientific investigations, such as studies investigating the history of zoonotic diseases. Our results provide important new information for interpreting these studies within a precise geographical framework.</p