Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy: programmatic implications for countries phasing out stavudine.

Background: The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure.

Susceptibility to etravirine of HIV type 1 subtype C isolates from nevirapine/efavirenz-experienced patients: comparative interpretation of ANRS and STANFORD algorithms.

Abstract We analyzed subtype C HIV-1 isolates from patients at failure of a regimen including nevirapine or efavirenz for their susceptibility or resistance to etravirine according to the ANRS and STANFORD algorithms. Statistical analysis showed a consensus that more than 45% of these viral strains are potentially resistant to etravirine.

Molecular characterization of non-B HIV type 1 isolates from patients of a department of infectious diseases, University Hospital of Bordeaux, France, 1989-2009.

The molecular characterization of non-B HIV type 1 subtypes and the sociodemographic baseline characteristics have been studied for 114 non-B HIV-1-infected patients followed at the University Hospital of Bordeaux, France, and diagnosed as HIV infected between 1989 and 2009. Individuals enrolled in this study were mainly women with heterosexual transmission in West and Central Africa and who have been discovered to be HIV positive during pregnancy. Nevertheless, HIV acquisition among individuals born in France was significantly increasing.

Drug resistance mutations in HIV type 1 isolates from naive patients eligible for first line antiretroviral therapy in JJ Hospital, Mumbai, India.

More than 50 HIV-1-infected patients, naive of antiretroviral therapy (ART) but eligible for first line ART in JJ Hospital, Mumbai, India were investigated for surveillance drug resistance mutations (SDRMs); all but one virus belonged to subtype C; we could observe SDRMs to nonnucleoside reverse transcriptase inhibitors and protease inhibitors in 9.6% of the patients.

First data on HIV-1 resistance mutations to antiretroviral drugs in Central African Republic.

In a background of high genomic HIV-1 variability with a predominance of CRF11_cpx and CRF22_01A1, we have studied the emergence of resistance mutations in isolates from Central African patients at failure of d4T-AZT/3TC/NVP-EFV plus two at failure of a PI-including regimen; the resistance mutations observed are those which are expected on HIV-1 subtype B.

Analysis of RT sequences of subtype C HIV-type 1 isolates from indian patients at failure of a first-line treatment according to clinical and/or immunological WHO guidelines.

The reverse transcriptase (RT) sequences of HIV-1 subtype C isolates from Indian patients at failure (according to WHO clinical or immunological criteria) of a first-line treatment including d4T/AZT-3TC-NVP/EFV were compared to those of HIV-1 isolates from naive patients and analyzed for drug resistance mutations (DRMs), which were interpreted according to ANRS and Stanford algorithms. All viruses were of subtype C. We have observed a decrease of the polymorphism at positions 36 and 214 of RT while D121Y, V179I, and Q217E could be new DRMs.

Variability and recombination of clinical human cytomegalovirus strains from transplantation recipients.

Background: Human cytomegalovirus (HCMV) is the first cause of viral infection in immunocompromised transplanted patients.

Objectives: Here, five HCMV genes were studied to investigate the existence of recombination events in clinical strains ex vivo.

Study Design: Sequencing and phylogenetic analysis were conducted on 21 strains from 16 renal and 5 lung transplant recipients.

Pol bootscanning analysis of HIV type 1 can exhibit unexpected recombinations.

In France the recommendation is to sequence the RT gene of HIV-1 isolates prior to initiation of antiretroviral therapy. The data are routinely used for molecular characterization of the viruses yielding the subtype or CRF of the isolates investigated together with the absence or presence of drug resistance mutations. In this study, we performed bootscanning analysis on the whole pol gene, in which in vitro and in vivo intersubtype recombination has been reported to occur frequently.

First observation of HIV type 1 drug resistance mutations in Algeria.

This study demonstrates for the first time HIV-1 resistance mutations to all classes of antiretroviral drugs available in Algeria (NRTIs, NNRTIs, PIs) in treated patients at failure. Moreover, it is shown that mutations to NRTIs and PIs can be observed in untreated patients in this country where there is high HIV-1 diversity.

Reverse transcriptase mutations in Cambodian CRF01_AE isolates after antiretroviral prophylaxis against HIV Type 1 perinatal transmission.

This study explores amino acid changes of the reverse transcriptase (rt) of CRF01_AE isolates from pregnant women naive to antiretroviral drugs before and 2, 6, and 52 weeks after exposure to single dose nevirapine (sdNVP). Results based on 51 observations showed that the proportion of isolates with nonnucleoside reverse transcriptase inhibitor (NNRTI) RMs in the group treated with sdNVP (n = 35) increased from 0% pre-NVP to 22.9% at week 2 postpartum (pp) and 22.

HIV-1 antiretroviral drug resistance in recently infected patients in Abidjan, Côte d'Ivoire: A 4-year survey, 2002-2006.

We performed HIV-1 drug resistance genotypic analysis of viral isolates from 100 antiretroviral (ARV)-naive, recently HIV-1-infected (between 2002 and 2006) individuals from Abidjan (Côte d'Ivoire). The overall prevalence of HIV-1 variants with resistance mutations to reverse transcriptase, protease, or fusion inhibitors was 6%. The majority of isolates were CRF02_AG.

Characterization of HIV-1 isolates from antiretroviral drug-naive children in southern India.

Access to antiretroviral therapy has expanded in many developing countries, including India. The standard first-line regimens consist of a combination of two nucleoside reverse transcriptase inhibitors and a nonnucleoside reverse transcriptase inhibitor, in a fixed drug combination. Data regarding resistance to these drugs are scarce, especially in children.

Resistance mutations in subtype C HIV type 1 isolates from Indian patients of Mumbai receiving NRTIs plus NNRTIs and experiencing a treatment failure: resistance to AR.

We present here the first data available on resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in India. In these subtype C isolates, we have observed most of the mutations noted in reverse transcriptase (RT) for subtype B with some additional substitutions (at positions 98, 203, 208, and 221) that will warrant attention in the algorithms used.

Virological characterization of an infection with a dual-tropic, multidrug-resistant HIV-1 and further evolution on antiretroviral therapy.

We studied a case of recent infection with multidrug-resistant (MDR) HIV-1. Over 16 months off-therapy, the CD4 cell count decreased from 419 to 184 cells/mul. Antiretroviral therapy (ART) then led to an incomplete virological response but to an immunological benefit, concurrently with a shift to CCR5-only tropism and a reduction in replication capacity.

High diversity of HIV type 1 in Algeria.

We have sequenced different genes of HIV-1 strains from infected individuals recruited in various geographic parts of Algeria; phylogenetic trees were constructed yielding molecular characterization of these strains. Subtype B accounts for 56% of the samples studied and is therefore the predominant subtype, particularly in the north part of the country; but there is a high diversity of the virus including CRF02_AG, CRF06_cpx, CRF02/CRF06 interrecombinants, and different other intersubtype and/or inter-CRF recombinants. The prevalence of these non-B viruses increases in the south part of Algeria that borders sub-Saharan African countries.

Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C viruses from untreated patients of Africa and Asia: comparative genotypic and phenotypic data.

Non-B HIV-1 viruses are predominant in developing countries where access to antiretroviral drugs (ARVs) is progressively being intensified. It is important to obtain more data on the susceptibility of these viruses to available ARVs. CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated patients from Vietnam, Cote d'Ivoire, and India were analyzed for their in vitro susceptibility to NRTIs, NNRTIs, PIs, and an entry inhibitor (T-20) using a recombinant viral assay (PHENOSCRIPT).

Characterization of mutations in HIV type 1 isolates from 144 Cambodian recently infected patients and pregnant women naive to antiretroviral drugs.

A baseline study has been conducted to determine the polymorphism of reverse transcriptase, protease, and envelope genes of HIV-1 isolates from 146 antiretroviral drug-naive Cambodian patients including 22 seroconverters and 124 pregnant women having been diagnosed HIV positive for less than 1 year. Amplification of at least one gene was successful for 144 isolates. All three genes were obtained for 136 isolates.

Characterization of nevirapine (NVP) resistance mutations and HIV type 1 subtype in women from Abidjan (Côte d'Ivoire) after NVP single-dose prophylaxis of HIV type 1 mother-to-child transmission.

Nevirapine (NVP) single dose is widely used in developing countries to prevent HIV-1 mother-to-child transmission. However, this regimen selects key drug resistance mutations that can impair further HAART efficacy. We studied the HIV-1 reverse transcriptase genotype from 29 Ivoirian women 1 month after an NVP single-dose prophylaxis.

Presence of CRF09_cpx and complex CRF02_AG/CRF09_cpx recombinant HIV type 1 strains in Côte d'Ivoire, West Africa.

Based on partial env and pol (protease and RT) subtyping, we recently documented that the majority (>80%) of the HIV-1 strains that circulate in Côte d'Ivoire were CRF02_AG and about 11% were recombinants or could not be clearly assigned to a known subtype or CRF. In order to determine in more detail the precise structure of these viruses we sequenced the full-length genomes for six such strains. Bootscan and phylogenetic tree analysis showed that four strains were complex and unique CRF02_AG/CRF09_cpx recombinants, one was a CRF02_AG/CRF06_cpx recombinant, and one was a pure CRF09_cpx.

In vitro photochemical inactivation of cell-associated human T-cell leukemia virus Type I and II in human platelet concentrates and plasma by use of amotosalen.

Background: Human T-cell leukemia virus Types I and II (HTLV-I and HTLV-II), blood-borne retroviruses found worldwide, can cause leukemia, immunosuppression, and severe neurologic diseases. In most countries, HTLV-I and -II screening is not performed systematically for blood donations. A new photochemical treatment (PCT) with a synthetic psoralen was developed to inactivate most pathogens in platelet (PLT) concentrates or plasma and to improve the safety of blood donations.

New insights in HTLV-I phylogeny by sequencing and analyzing the entire envelope gene.

The HTLV-I envelope plays a major role in the process of target cell infection. It is implied in the recognition of the viral receptor(s), penetration of the viral genetic material, and induction of host immunity to the virus. It is thus important to study the genetic variability of the viral env gene as well as its variation in terms of evolution.

Molecular characterization, phylogenetic relationships, and developmental expression patterns of prion genes in zebrafish (Danio rerio).

Prion diseases are characterized by the accumulation of a pathogenic misfolded form of a prion protein (PrP) encoded by the Prnp gene in humans. In the present study in zebrafish, two transcripts and the corresponding genes encoding prion proteins, PrP1 and PrP2, related to human PrP have been characterized with a relatively divergent deduced amino acid sequence, but a well preserved overall organization of structural prion protein motifs. Whole-mount in situ hybridization analysis performed during embryonic and larval development showed a high level of PrP1 mRNA spatially restricted to the anterior floor-plate of the central nervous system and in ganglia.

Molecular characterization of HIV type 1 isolates from untreated patients of Mumbai (Bombay), India, and detection of rare resistance mutations.

The molecular characterization of HIV-1 isolates in drug-naive cases in the early stages of HIV disease was studied in 128 cases from Mumbai (Bombay), India. Subtype C was largely predominant followed by A-C intersubtype recombinants, one subtype A and one CRF01 AE. Compared to subtype B, subtype C exhibited an important polymorphism; the percentages of substitutions could reach more than 90%.