Impact of Human Immunodeficiency Virus Type 1 Minority Variants on the Virus Response to a Rilpivirine-Based First-line Regimen.

Background: Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR). Methods: All the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load <50 copies/mL at month 6 with continued suppression at month 12. NGS was performed at baseline (retrospectively) on the 454 GS-FLX platform (Roche). Results: NGS revealed resistance-associated mutations accounting for 1% to <5% of variants in 17.2% of samples, for 5%-20% in 5.7% of samples, and for >20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count <250 cells/µL at baseline, a slower decrease in viral load at month 3, and rilpivirine resistance at baseline using the Stanford algorithm with a 20% threshold. Conclusions: Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.

[Cancers of the upper aerodigestive tract associated with human papillomavirus]. / Les cancers des voies aérodigestives supérieures associés aux papillomavirus.

Carcinomas of the aerodigestive tract are most often secondary to alcohol and tobacco intoxication. However, it is shown that the oncogenic human papillomavirus (HPV) have an increasing role in the carcinogenesis of these cancers. Patients with HPV+ carcinoma are generally younger and not alcohol and tobacco users. These carcinomas are mainly localized in the oropharynx and in particular at the tonsil. HPV is found in 40 to 90 % of the cancers in the oropharynx, depending on the country. These HPV+ carcinomas have a better prognosis with better radio or chemosensitivity. To date, no change of treatment is recommended, however, several trials are underway. Preventive vaccination of boys is a real public health issue, especially since it is recommended in some countries. Moreover, a better understanding of the tumor microenvironment will ultimately offer therapeutic vaccination.

Value of cytologic Papanicolaou smears and polymerase chain reaction screening for human papillomavirus DNA in detecting anal intraepithelial neoplasia: comparison with histology of a surgical sample.

BACKGROUND: The performance of cytologic screening and its correlation with histology and polymerase chain reaction (PCR) detection of human papillomavirus (HPV) DNA have not been evaluated in populations with a low prevalence of anal intraepithelial neoplasia (AIN). The objective of the current study was to analyze the significance of abnormal smears relative to the histology and PCR detection of HPV DNA. METHODS: A cytologic smear and a viral sample were taken in 300 consecutive patients undergoing surgery (Milligan-Morgan hemorrhoidectomy and/or fissurectomy) who gave their informed consent. RESULTS: The cytologic smear was normal in 216 of 290 patients (74.5%). Four high-grade and 19 low-grade intraepithelial neoplastic lesions were identified. In 5 patients, high-grade lesions could not be excluded, 30 lesions were of undetermined significance, and there were 16 cellular modifications with a non-neoplastic appearance. The PCR test for HPV was positive in 18.7% of patients, and a high-risk genotype was identified in 63.6% of positive samples. Histologic examination of the surgical samples was normal in 92.3% of patients. The 23 AIN samples were distributed as follows: 13 grade 1 AIN (AIN1), 6 AIN2, and 4 AIN3. The sensitivity of cytologic smears and PCR for detecting AIN was 56% and 60.8%, respectively, and specificity was 77% and 84.5%, respectively. Combining the 2 tests increased sensitivity to 78% but decreased specificity to 68%. CONCLUSIONS: Compared with a large surgical sample, anal cytologic Papanicolaou smears and HPV PCR exhibited sensitivity and specificity that varied, depending on the risk of HPV infection and AIN. Positive HPV DNA screening increased with AIN grade, and high-risk HPV testing was particularly helpful.

Dynamics of enfuvirtide resistance mutations in enfuvirtide-experienced patients remaining in virological failure under salvage therapy.

BACKGROUND: Evaluation of the dynamics of enfuvirtide (ENF) resistance mutations after ENF withdrawal in patients with virological failure under salvage therapy may be helpful to optimize the management of ENF in human immunodeficiency virus (HIV)-infected patients. METHODS: Seven patients with a failing ENF-containing regimen, initiated for at least 3 months (median 6.4 months, range 3-14), were included and followed up prospectively at the time of virological failure. Genotypic analysis of the gp41 region by bulk sequencing and clonal analysis was performed in plasma and/or peripheral blood mononuclear cells to detect ENF resistance mutations. RESULTS: Genotypic profiles of ENF-resistant variants at ENF discontinuation were as follows: V38A in 3 patients, V38A+N42T+N43D in 1 patient, N43D in 2 patients, and N43K in 1 patient. Clonal analysis showed that maintaining ENF treatment after virological failure has an impact on both (1) the number of resistance profiles detected, and (2) the time of persistence of ENF-resistant variants. ENF-resistant variants were archived in HIV DNA in 5/7 patients. At 1 month after ENF withdrawal, no significant increase in HIV-1 viral load was observed. CONCLUSION: The persistence of ENF-resistant variants was found to be correlated to exposure time to failing drug. ENF withdrawal should be considered in patients with virological failure to preserve the possible efficacy of ENF recycling or upcoming entry inhibitors.

High frequency of antiretroviral drug resistance among HIV-infected adults receiving first-line highly active antiretroviral therapy in N'Djamena, Chad.

Antiretroviral drug resistance was evaluated in 88 adults infected with human immunodeficiency virus, most with subtype CRF11_cpx, who had received a first-line antiretroviral regimen for 6 months, in N'Djamena, Chad. A total of 47 patients (53%) had detectable viral load at month 6, and 56 (64%) had at least 1 antiretroviral resistance mutation observed.

Evaluation of the one-step multiplex real-time reverse transcription-PCR ProFlu-1 assay for detection of influenza A and influenza B viruses and respiratory syncytial viruses in children.

We evaluated the one-step multiplex real-time reverse transcription-PCR ProFlu-1 assay for the detection of influenza A and influenza B viruses and respiratory syncytial viruses from 353 pediatric nasopharyngeal aspirates. As assessed by comparison with the results of immunofluorescence testing and cell culture, the specificity and the sensitivity of the ProFlu-1 assay ranged from 97% to 100%. In addition, the ProFlu-1 assay amplified 9% of samples not detected by conventional methods.

Foscarnet salvage therapy efficacy is associated with the presence of thymidine-associated mutations (TAMs) in HIV-infected patients.

BACKGROUND: Salvage therapy based on foscarnet plus a thymidine analog is effective in patients with advanced-stage HIV disease and viruses harbouring multiple drug-resistance mutations. OBJECTIVE: To identify viral genetic determinants associated with the virological efficacy of foscarnet salvage therapy. STUDY DESIGN: Thirteen patients received foscarnet at a fixed dose of 80 mg/kg twice daily for 14 days, in combination with zidovudine or stavudine. RESULTS: The baseline median HIV viral load and CD4 cell count were 5.10log(10) copies/ml and 23 cells/mm(3), respectively. Following foscarnet therapy, viral load fell by a median of 1.84log(10)copies/ml (range: -0.29 to -2.82), and by at least 1log(10)copies/ml in 11 patients, all of whom harboured viruses with at least three thymidine-associated mutations (TAMs). The two patients with smaller declines in viral load (<0.50log(10)copies/ml) harboured viruses with only one or zero TAMs. CONCLUSIONS: These findings corroborate, in vivo, the impact of TAMs on HIV susceptibility to foscarnet. The virological response to foscarnet salvage therapy in multiclass-experienced patients may thus differ according to the number of TAMs.

Early archives of genetically-restricted proviral DNA in the female genital tract after heterosexual transmission of HIV-1.

OBJECTIVES AND METHOD: In order to characterize human immunodeficiency virus type 1 (HIV-1) variants that are transmitted in women via heterosexual intercourse, the env V1-V3 sequences of HIV-1 provirus (DNA) and free virus (RNA) in paired samples of blood and cervicovaginal secretions of untreated chronically and primary infected African women were compared. RESULTS: Env RNA sequences retrieved from plasma and genital compartments formed a single cluster in primary infection. In contrast, env RNA sequences from these two compartments were distinct in chronically infected women. Analysis of proviral DNA of primary infected women showed that most HIV-1 sequences derived from the genital epithelia form independent clusters from HIV-1 sequences of DNA from peripheral blood mononuclear cells and RNA recovered from plasma and genital secretions. Similarly, the analysis of proviral DNA in the genital compartment of chronically infected women showed the persistence of genetically-restricted cluster of HIV-1. CONCLUSIONS: These observations indicate that a viral subpopulation is archived as proviral DNA in the female genital tract early in primary infection, and suggest that HIV-1 variants from the male donor are selected in the female mucosal site during male to female transmission of HIV-1.

HSV-2- and HIV-1- permissive cell lines co-infected by HSV-2 and HIV-1 co-replicate HSV-2 and HIV-1 without production of HSV-2/HIV-1 pseudotype particles.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a major cofactor of human immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the present study, we investigated whether HIV-1 and HSV-2 may interact at the cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope glycoproteins, as was previously reported for HSV type 1. METHODS: We evaluated in vitro the production of HSV-2/HIV-1 pseudotypes in mononuclear CEM cells and epithelial HT29 and P4P cells. We analyzed the incorporation into the HIV-1 membrane of HSV-2 gB and gD, two major HSV-2 glycoproteins required for HSV-2 fusion with the cell membrane, in co-infected cells and in HIV-1-infected P4P cells transfected by plasmids coding for gB or gD. RESULTS: We show that HSV-2 and HIV-1 co-replicated in dually infected cells, and gB and gD were co-localized with gp160. However, HIV-1 particles, produced in HIV-1-infected cells expressing gB or gD after transfection or HSV-2 superinfection, did not incorporate either gB or gD in the viral membrane, and did not have the capacity to infect cells normally non-permissive for HIV-1, such as epithelial cells. CONCLUSION: Our results do not support the hypothesis of HSV-2/HIV-1 pseudotype formation and involvement in the synergistic genital interactions between HIV-1 and HSV-2.

Unexpected high prevalence of herpes simplex virus (HSV) type 2 seropositivity and HSV genital shedding in pregnant women living in an East Paris suburban area.

Both herpes simplex virus type 2 (HSV-2) seroprevalence and the proportion of HSV-1 genital ulcers are increasing in industrialized countries. The consequences of these epidemiological changes, in pregnant women in France, for both the genital shedding of HSV and vertical transmission, have been poorly evaluated. The HSV-1 and HSV-2 seroprevalence and the rate of subclinical genital shedding of herpes close to delivery were evaluated in pregnant women, with no history of genital herpes, living in the East Paris suburban area. HSV-2 antibody prevalence of 26% was significantly associated with country of origin and was higher than that reported in 2002 in French women from the general population (18%). HSV-2 and HSV-1 genital reactivations were observed in 10% of HSV-2 seropositive and in 4% of HSV-1 seropositive and HSV-2 seronegative women, respectively. The high rates of HSV-2 seropositivity and subclinical herpes genital shedding observed in this study should be considered to promote a national survey in pregnant women to propose strategies to prevent the spread of HSV within the population and to the neonate.

Detection and quantitation of BK virus DNA by real-time polymerase chain reaction in the LT-ag gene in adult renal transplant recipients.

Determination of polyomavirus BK (BKV) load in urine and plasma has been advocated for monitoring adult renal transplant recipients suffering from BKV-related nephropathy. An "in-house" real-time quantitative PCR assay was developed using the BKV-1/BKV-3 primers set in the large tumor antigen (LT-ag) region to quantitate BK virus loads in plasma and urine in renal transplant patients. This assay was adapted to routine virology laboratory by evaluating two extraction procedures of nucleic acids from urine and plasma, one manual and the other using an automatic extractor, and by evaluating the Light Cycler versus Taqman apparatus. Both the manual and automatic extraction procedures and real-time PCR apparatus were equivalent. The Light Cycler and Taqman instruments allow similarly rapid, accurate, reproducible and specific quantitative detection of the three major BKV subtypes, with a detection limit of 10 BKV DNA copies/ml, and a range from 10(0) to 10(7) copies/ml. Of 855 renal transplant patients, 128 (15%) had BKV DNA in both plasma and urine samples with a mean viral load of 5.1 log/ml in plasma and 6.8 log/ml in urine and in 5 (4%) BKV-associated tubulo-interstitial nephropathy; 332 (39%) BKV DNA was found only in the urine, not in the plasma, without further development of nephropathy and 395 patients had no BKV in plasma and urine. These observations emphasize the usefulness of real-time PCR to assess the BKV load by routine testing, and confirm the need to combine both plasma and urine determinations of the BKV DNA load in order to identify renal transplant patient at high risk for BKV-associated nephropathy.

Genital shedding of herpes simplex virus type 2 in childbearing-aged and pregnant women living in Gabon.

The prevalence of genital shedding of herpes simplex virus (HSV)-2 and related risk factors was evaluated in a prospective population of 355 women attending the Maternity Joséphine Bongo, in Libreville, Gabon. We found a high prevalence (66%) of HSV-2 seropositivity, with a high proportion, 14%, of women harbouring HSV-2 DNA shedding in their genital secretions. HSV-2 genital shedding was positively associated with previous episodes of genital blisters, current genital ulcer, current genital blister, HIV seropositivity and HSV-2 seropositivity. The high prevalence of HSV-2 in childbearing-aged population indicates that young women living in Gabon are at high risk for HIV acquisition in HIV-seronegative women sexually exposed to HIV, for HIV transmission in HIV-infected women co-infected by HSV-2 and finally for HSV-2 vertical transmission during pregnancy.

Cell-associated, non-replicating strand(+) hepatitis C virus-RNA shedding in cervicovaginal secretions from chronically HCV-infected women.

BACKGROUND: Lack of mucosal hepatitis C virus (HCV) transmission may be due to fairly low infectivity of body fluids in HCV-infected individuals in association with yet unknown innate or acquired resistance factors in individuals exposed to the virus. OBJECTIVE: To evaluate HCV excretion patterns in cervicovaginal secretions obtained from chronically HCV-infected women. STUDY DESIGN: Fifteen chronically HCV-infected women of childbearing age hospitalized for chronic hepatitis were prospectively recruited. Cervicovaginal secretions were obtained by vaginal washing with 3 ml phosphate-buffered saline (PBS). All cervicovaginal secretions were free of hemoglobin traces and also free of semen traces. Free HCV-RNA and cell-associated HCV-RNA were examined in acellular part and cellular part of the cervicovaginal secretions, respectively, by in-house qualitative PCR for 5'-HCV-non-coding region (NCR). Negative strand HCV-RNA, a marker of HCV replication, was searched by using tag-RT-nested PCR (tag-RT-NPCR). RESULTS: HCV-RNA could not be detected in the acellular fractions of the 15 evaluated cervicovaginal secretions. In contrast, HCV-RNA could be detected in the cellular fractions of four of 15 (27%) cervicovaginal secretions. None of the cervicovaginal secretions, including the four positive cell-associated HCV-RNA, contained negative strand, replicating HCV-RNA. CONCLUSIONS: Our results suggest that positive strand HCV-RNA may be present outside the menstruation periods as cell-associated virus in the cervicovaginal secretions of a minority of untreated HCV-seropositive, HCV-RNA-viremic women, and that the lower female genital tract does not constitute a reservoir where HCV replicates. These observations thus provide the basis for the low risk of female-to-male sexual transmission of HCV infection.

Lack of regression of anal squamous intraepithelial lesions despite immune restoration under cART.

BACKGROUND: A high prevalence of anal squamous intraepithelial lesions (ASIL) and human papillomavirus (HPV) infections were observed in HIV-infected men who have sex with men (MSM) in the precART (combined antiretroviral therapy) era. The impact of cART on the natural history of HPV infection and ASIL is poorly documented. METHODS: Ninety-four HIV-infected MSM naive of cART were enrolled in a longitudinal study before starting cART. Patients were evaluated for anal cytology, histology and anal HPV DNA at baseline, month 12 and month 24 of cART. HPV DNA genotyping was performed by Linear Array assay. Anal cytologic samples were processed by the Thin Prep method. RESULTS: Analyses included 76 patients with at least two visits with available cytology. The median age was 39.4 years. The median (interquartile range) CD4 cell count was 301 cells/µl (242-339) at baseline and 545 cells/µl at month 24, when 93% of patients had plasma HIV-RNA 50 copies/ml or less. An abnormal result was observed in 45 of 76 patients at baseline (59%) with prevalent low-grade squamous intraepithelial lesion (LSIL) in 27 patients (36%) and high-grade squamous intraepithelial lesion (HSIL) in seven patients (9%) and in 36 of 69 patients assessed at month 24 (52%) with LSIL in 23 patients (33%) and HSIL in six patients (9%). At month 24, regression of the severity of lesions was observed in 44% of patients, whereas a lesion occurred in 37% of patients. CONCLUSION: Our results show a high prevalence and incidence of ASIL in HIV-infected MSM despite immune restoration under cART. These data emphasize that HIV-positive MSM although receiving effective cART remain at high risk of anal squamous intra-epithelial lesions.

A cohort study of treatment-experienced HIV-1-infected patients treated with raltegravir: factors associated with virological response and mutations selected at failure.

This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on VR of baseline integrase mutations, VL, CD4 count, genotypic sensitivity score for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the number of new antiretrovirals used for the first time associated with RAL were investigated. For patients with VL >50 copies/mL at M6, integrase mutations selected were characterised. Median baseline VL was 4.2 log(10)copies/mL (IQR 3.3-4.9 log(10) copies/mL) and CD4 count was 219 cells/mm(3) (IQR 96-368 cells/mm(3)). At M6, 71% of patients were responders. In multivariate analysis, baseline VL and CD4 count and ≥ 2 new antiretrovirals among darunavir, etravirine, maraviroc and enfuvirtide were associated with VR to RAL. Neither HIV-1 subtype nor baseline integrase polymorphisms were associated with VR to RAL. Among 63 failing patients at M6, selection of ≥ 1 change in the integrase gene was observed in 49 (77.8%), and 27/63 (42.9%) were considered as RAL-associated resistance mutations. Factors independently associated with the occurrence of ≥ 1 RAL-associated resistance mutation were VL at failure >3 log(10) and having no new drugs associated with RAL. RAL showed great potency in treatment-experienced patients. The number of new drugs associated with RAL was an important factor associated with VR. HIV-1 subtype and baseline integrase polymorphisms do not influence the RAL VR.

PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer.

Head and neck cancers positive for human papillomavirus (HPV) have a more favorable clinical outcome than HPV-negative cancers, but it is unknown why this is the case. We hypothesized that prognosis was affected by intrinsic features of HPV-infected tumor cells or differences in host immune response. In this study, we focused on a comparison of regulatory Foxp3(+) T cells and programmed death-1 (PD-1)(+) T cells in the microenvironment of tumors that were positive or negative for HPV, in two groups that were matched for various clinical and biologic parameters. HPV-positive head and neck cancers were more heavily infiltrated by regulatory T cells and PD-1(+) T cells and the levels of PD-1(+) cells were positively correlated with a favorable clinical outcome. In explaining this paradoxical result, we showed that these PD-1(+) T cells expressed activation markers and were functional after blockade of the PD-1-PD-L1 axis in vitro. Approximately 50% of PD-1(+) tumor-infiltrating T cells lacked Tim-3 expression and may indeed represent activated T cells. In mice, administration of a cancer vaccine increased PD-1 on T cells with concomitant tumor regression. In this setting, PD-1 blockade synergized with vaccine in eliciting antitumor efficacy. Our findings prompt a need to revisit the significance of PD-1-infiltrating T cells in cancer, where we suggest that PD-1 detection may reflect a previous immune response against tumors that might be reactivated by PD-1/PD-L1 blockade.

Characterization and whole genome analysis of human papillomavirus type 16 e1-137463nt variants.

BACKGROUND: The variation of the most common Human papillomavirus (HPV) type found in cervical cancer, the HPV16, has been extensively investigated in almost all viral genes. The E1 gene variation, however, has been rarely studied. The main objective of the present investigation was to analyze the variability of the E6 and E1 genes, focusing on the recently identified E1-1374^63nt variant. METHODOLOGY/PRINCIPAL FINDINGS: Variation within the E6 of 786 HPV16 positive cervical samples was analyzed using high-resolution melting, while the E1-1374^63nt duplication was assayed by PCR. Both techniques were supplemented with sequencing. The E1-1374^63nt duplication was linked with the E-G350 and the E-C109/G350 variants. In comparison to the referent HPV16, the E1-1374^63nt E-G350 variant was significantly associated with lower grade cervical lesions (p = 0.029), while the E1-1374^63nt E-C109/G350 variant was equally distributed between high and low grade lesions. The E1-1374^63nt variants were phylogenetically closest to E-G350 variant lineage (A2 sub-lineage based on full genome classification). The major differences between E1-1374^63nt variants were within the LCR and the E6 region. On the other hand, changes within the E1 region were the major differences from the A2 sub-lineage, which has been historically but inconclusively associated with high grade cervical disease. Thus, the shared variations cannot explain the particular association of the E1-1374^63nt variant with lower grade cervical lesions. CONCLUSIONS/SIGNIFICANCE: The E1 region has been thus far considered to be well conserved among all HPVs and therefore uninteresting for variability studies. However, this study shows that the variations within the E1 region could possibly affect cervical disease, since the E1-1374^63nt E-G350 variant is significantly associated with lower grade cervical lesions, in comparison to the A1 and A2 sub-lineage variants. Furthermore, it appears that the silent variation 109T>C of the E-C109/G350 variant might have a significant role in the viral life cycle and warrants further study.

An unusual human papillomavirus type 82 detection in laryngeal squamous cell carcinoma: case report and review of literature.

Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescent or younger adult and typically has an aggressive nature. The mechanism of laryngeal oncogenesis is complex and little is known about the role of human papillomaviruses (HPVs) in SCC in young age. HPV infection may occur during birth or latter by oro-genital contact. Most HPV genotypes detected were HPV 6, 11, 16, 18, 33 and 51. Herein, we report a case of invasive laryngeal SCC expressing an HPV 82 in an 18 year-old man with a history of unexplored severe acute dysphonia that started in early childhood.

Virological failure and HIV type 1 drug resistance profiles among patients followed-up in private sector, Douala, Cameroon.

The rate of virological failure was assessed in 819 patients followed up by the private sector of Douala, the economic capital of Cameroon, and treated according to the World Health Organization (WHO) recommendations. In addition, genotypic resistance testing was carried out in the subgroup of 75 selected patients representative of the 254 patients in virological and/or immunological failure receiving a first-line (83%) or second-line (17%) regimen. Overall, 36% of patients treated by antiretroviral drugs (ARV) were in virological failure, as assessed by plasma viral load above 3.7 log(10) copies/ml under treatment for more than 6 months. According to the immunological status, 17% of patients showed a CD4 T cell count under 200 cells/mm(3) and 37% under 350 cells/mm(3), indicating either ongoing immunorestoration or immunological failure under treatment. Twenty percent of patients in virological failure showed wild-type viruses susceptible to all ARV, likely indicating poor adherence. However, 80% of them displayed plasma virus resistant at least to one ARV drug, mostly to the nucleoside reverse transcriptase inhibitors (NRTIs) class (80%), followed by the non-NRTI class (76%) and the protease inhibitor class (19%), thus reflecting the therapeutic usage of ARV drugs in Cameroon as recommended by the WHO. Whereas the second-line regimen proposed by the 2009 WHO recommendations could be effective in more than 75% of patients in virological failure with resistant viruses, the remaining patients showed a resistance genotypic profile highly predictive of resistance to the usual WHO second-line regimen, including in some patients complex genotypic profiles diagnosed only by genotypic resistance tests. In conclusion, our observations highlight the absolute need for improving viral load assessment in resource-limited settings to prevent and/or monitor therapeutic failure.

Distribution of HIV-1 and HSV-2 epidemics in Chad revealing HSV-2 hot-spot in regions of high-risk HIV spread.

INTRODUCTION: Herpes Simplex Virus-2 (HSV-2) is known to be a potent co-factor of Human Immunodeficiency type 1 virus (HIV-1) heterosexual transmission. We were interested in assessing the distribution of HIV-1 and HSV-2 epidemics at the national level in Chad. METHODOLOGY: In 2007, a population-based anonymous serosurvey for HIV-1 and HSV-2 infections, using dried blood spots, was conducted. The study included 548 adults living in 15 regions of Chad. After specimen elution, serological testing for HIV and HSV-2 infections was performed. RESULTS: Countrywide, the HIV-1 and HSV-2 seroprevalences were 11.1% and 15.7%, respectively. A positive correlation was observed with the highest HIV-1 prevalence seen in regions of the highest HSV-2 prevalence, especially in two conflict-affected eastern provinces of Darfur. CONCLUSION: Urgent public health interventions are needed in regions of Chad where high HSV-2 prevalence may be increasing the risk of HIV propagation.