Characterization of HIV-1 genotypes and antiretroviral drug-resistance mutations among patients in Burkina Faso.

The purposes of this study were: (1) to describe the genetic variability of HIV strains found in Burkina Faso, (2) to characterize non-B HIV strains mutation profiles selected by ARVs and (3) to detect possible resistances induced by ARV drugs. From 30 October 2002 to 20 November 2003, 132 HIV 1-positive patients taking Highly Active Antiretroviral Therapy (HAART) for more than one year in Bobo-Dioulasso and Ouagadougou were included. T-CD4+ lymphocytes count was done using Dynabeads technique while genotypic test and ARV-resistance tests were conducted using Pol sequencing that codes for reverse transcriptase reverse, integrase and protease.

Low prevalence of HIV type 1 drug resistance mutations in untreated, recently infected patients from Burkina Faso, Côte d'Ivoire, Senegal, Thailand, and Vietnam: the ANRS 12134 study.

The frequency of transmitted HIV drug resistance (HIVDR) was evaluated in the context of rapid scale-up of antiretroviral treatment in Thailand, Vietnam, Burkina Faso, Côte d'Ivoire, and Senegal by using an adaptation of the WHO generic protocol of the HIV Drug Resistance Threshold Survey (HIVDR-TS) for sample collection and classification. Resistance-associated mutations were interpreted using the 2009 WHO list for epidemiological surveys. We included 266 subjects from the five study sites.

Evaluation of transmitted HIV drug resistance among recently-infected antenatal clinic attendees in four Central African countries.

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.

Long-term safety, effectiveness and quality of a generic fixed-dose combination of nevirapine, stavudine and lamivudine.

We assessed the long-term safety, effectiveness and quality of a fixed-dose combination of nevirapine, stavudine and lamivudine (triomune). HIV-1-infected adults initially enrolled in a one-year, open-label, single-arm, multicentre trial in Cameroon were followed for 2 years. Our results support the safety and effectiveness of the triomune combination for first-line treatment of HIV infection.

Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus.

Background: Epidemiologic data suggest that infection with herpes simplex virus type 2 (HSV-2) is associated with increased genital shedding of human immunodeficiency virus type 1 (HIV-1) RNA and HIV-1 transmissibility.

Methods: We conducted a randomized, double-blind, placebo-controlled trial of HSV suppressive therapy with valacyclovir (at a dose of 500 mg twice daily) in Burkina Faso among women who were seropositive for HIV-1 and HSV-2; all were ineligible for highly active antiretroviral therapy. The patients were followed for 24 weeks (12 weeks before and 12 weeks after randomization).

Impact of suppressive herpes therapy on genital HIV-1 RNA among women taking antiretroviral therapy: a randomized controlled trial.

Objective: To demonstrate a causal relationship between herpes simplex virus 2 (HSV-2) and increased genital HIV-1-RNA shedding in women on HAART.

Design: A randomized, double-blind, placebo-controlled trial of herpes-suppressive therapy (valacyclovir 500 mg twice a day) in HIV-1/HSV-2-infected women taking HAART in Burkina Faso.

Methods: Participants were followed for a total of 12 biweekly visits before and after randomization.

Antiretroviral drug resistance and routine therapy, Cameroon.

Among 128 patients routinely receiving highly active antiretroviral therapy in an HIV/AIDS outpatient clinic in Cameroon, 16.4% had drug resistance after a median of 10 months. Of these, 12.

Natural polymorphism in protease and reverse transcriptase genes and in vitro antiretroviral drug susceptibilities of non-B HIV-1 strains from treatment-naive patients.

Background: Most studies on antiretroviral (ARV) resistance of human immunodeficiency virus (HIV) have been done on subtype B which only represent a limited proportion of infections worldwide.

Objective: Understand baseline susceptibilities to ARVs in non-B strains.

Methods: To explore in greater detail possible intrinsic resistance to antiretroviral drugs in non-B subtypes, phenotypic resistance was tested in 35 non-B (A, D, F, G, J; CRF02, 06, 09, 11, 13) HIV-1 isolates obtained from ARV treatment naive patients.

Optimization of a genotypic assay applicable to all human immunodeficiency virus type 1 protease and reverse transcriptase subtypes.

Genotypic assays are used often to guide clinicians in decisions concerning the treatment of patients. An optimized sequence-based genotypic assay was used to determine the whole protease and reverse transcriptase (RT) gene, including the gag cleavage site region and RNase H region. Since non-B subtypes are increasing in countries where subtype B was the most prevalent subtype, and treatment becomes more available in developing countries where the epidemic is characterized by a high prevalence of non-B subtypes, it was important that the genotypic test was evaluated using a panel of different subtypes.

Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults.

Objectives: To assess the long-term survival, as well as the immunologic and virologic effectiveness, adherence, and drug resistance, in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in one of the oldest and best-documented African cohorts.

Methods: A prospective observational cohort study included the first 176 HIV-1-infected adults followed in the Senegalese government-sponsored antiretroviral therapy initiative launched in August 1998. Patients were followed for a median of 30 months (interquartile range, 21-36 months).

Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy.

Objective: To monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART).

Methods: A total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes.

Biological and genetic characteristics of HIV infections in Cameroon reveals dual group M and O infections and a correlation between SI-inducing phenotype of the predominant CRF02_AG variant and disease stage.

In Yaounde, Cameroon, HIV-1 group-specific V3 serology on 1469 HIV-positive samples collected between 1996 and 2001 revealed that group O infections remained constant around 1% for 6 years. Only one group N sample was identified and 4.3% reacted with group M and O peptides.

The Senegalese government's highly active antiretroviral therapy initiative: an 18-month follow-up study.

Objective: To study the feasibility, effectiveness, adherence, toxicity and viral resistance in an African government HAART initiative.

Methods: A prospective observational cohort study started in Dakar in August 1998. Initial treatment consisted of two nucleoside reverse transcriptase inhibitors and one protease inhibitor.

CRF06-cpx: a new circulating recombinant form of HIV-1 in West Africa involving subtypes A, G, K, and J.

Phylogenetic analysis of numerous strains of HIV-1 isolated from diverse geographic origins has revealed three distinct groups of HIV-1: groups M, N, and O. Within group M, subtypes, sub-subtypes and circulating recombinant forms (CRFs) exist. Recently, two near-full-length genomes of similar complex mosaic viruses containing fragments of subtypes A, G, I, and J were described in patients from Burkina Faso (BFP-90) and Mali (95ML-84).

Development and evaluation of a DNA enzyme immunoassay method for env genotyping of subtypes A through G of human immunodeficiency virus type 1 group M, with discrimination of the circulating recombinant forms CRF01_AE and CRF02_AG.

The tools currently available for genetic subtyping of human immunodeficiency virus type 1 are laborious or can be used only for the analysis of a limited number of samples and/or subtypes. We developed and evaluated a molecular biology-based method using subtype-specific oligonucleotide probes for env genotyping of subtypes A through G, CRF01_AE, and CRF02_AG. DNA enzyme immunoassay (DEIA) genotyping is based on nested PCR amplification of the 5' end of the env gene (proviral DNA), followed by subtype-specific hybridization and immunoenzymatic detection on microplates.

Identification of a new circulating recombinant form of HIV type 1, CRF11-cpx, involving subtypes A, G, J, and CRF01-AE, in Central Africa.

In this study, we characterized three full-length genome sequences with a similar mosaic structure from epidemiologically unlinked individuals from Cameroon (97CM-MP818) and the Central African Republic (99CF-MP1298 and 99CF-MP1307). Phylogenetic and recombinant analysis confirmed that the three strains had a similar complex recombinant genome, which we can designate now as CRF11-cpx. This new CRF was composed of successive fragments of subtype A, G, J, and CRF01-AE.

Resistance to antiretroviral treatment in Gabon: need for implementation of guidelines on antiretroviral therapy use and HIV-1 drug resistance monitoring in developing countries.

The protease and reverse transcriptase (RT) genes were studied in antiretroviral (ARV)-experienced and drug-naive HIV-1-infected individuals in Libreville, Gabon. We have shown, although on a limited number of samples that in 58% (11/19) of the patients, with a mean of 17.7 months of ARV drug experience, major mutations inevitably inducing resistances to ARV drugs were present.

Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis independently of Fas signaling.

Apoptosis of CD4(+) T lymphocytes, induced by contact between human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (gp120) and its receptors, could contribute to the cell depletion observed in HIV-infected individuals. CXCR4 appears to play an important role in gp120-induced cell death, but the mechanisms involved in this apoptotic process remain poorly understood. To get insight into the signal transduction pathways connecting CXCR4 to apoptosis following gp120 binding, we used different cell lines expressing wild-type CXCR4 and a truncated form of CD4 that binds gp120 but lacks the ability to transduce signals.

Patterns of resistance mutations to antiretroviral drugs in extensively treated HIV-1-infected patients with failure of highly active antiretroviral therapy.

Resistance-mutation patterns in the reverse transcriptase (RT) and protease genes of HIV-1 were analyzed in 22 patients who had been extensively pretreated and who failed to respond to highly active antiretroviral therapy (HAART). The number of mutations ranged from 8 to 19 (median, 13): 4 to 12 (median, 6) mutations in the RT gene, and 4 to 8 (median, 7) mutations in the protease gene. In the RT gene, the most frequent resistance mutations were found at codons 215 (100%), 41 (95%), 67 (91%), and 210 (77%).