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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.

BACKGROUND Sequence variations in HR-1 gp41 env gene region encoding the target for T-20 have previously been reported among patients naive to inhibitory fusion. OBJECTIVE To evaluate whether a previous therapeutic history of patients could have an impact on a differential evolution of the gp41 polymorphism. METHODS We assessed the genetic polymorphism within the critical HR-1 gp41 env gene region in HIV-1 variants from 108 T-20-naive patients (Groups I-III) and 12 patients receiving T-20 as part of a salvage regimen (Group IV). T-20-naive patients included 50 patients exhibiting variants harboring resistance mutations to NRTIs, NNRTIs, and PIs (Group I), 24 patients with variants harboring resistance mutations for NRTIs and/or NNRTIs (Group II), and 34 antiretroviral drug-naive patients (Group III). RESULTS In T-20-naive patients whose HIV harbored resistance mutations to NRTIs, NNRTIs, and/or PIs, the mean number of synonymous mutations (ds) per patient was decreased and the mean number of nonsynonymous (da) mutations per patient was increased, resulting in a significant decrease in the mean Sigmads/Sigmada ratio as compared with antiretroviral drug-naive patients (Group III; 4.1 vs. 11.6; P < 0.0001). The mean number of polymorphic mutations in HR-1 gp41 per patient was two-fold higher in patients exhibiting antiretroviral drug resistance mutations (Groups I and II) than in antiretroviral drug-naive patients (Group III; 0.41 vs. 0.20; P < 0.05). CONCLUSION Our observations indicate that the HR-1 gp41 T-20 target is subjected to high genetic variability, including intrinsic polymorphism and selection of T-20 resistance mutations under T-20 intake, that is increased by the presence of resistance mutations to NRTIs, NNRTIs, and/or PIs. Our data provide a basis for a potential impact of previous antiretroviral drug history on the therapeutic efficacy of T-20.

The accuracy and usefulness of laboratory-developed real-time PCR procedures using a Light Cycler instrument (Roche Diagnostics) for detecting and quantifying human immunodeficiency virus type 1 (HIV-1) RNA and DNA as well as herpes simplex virus type 1 (HSV-1)/HSV-2 DNA in cervicovaginal secretions from women coinfected with HIV and HSV were evaluated. For HIV-1, the use of the NEC152 and NEC131 primer set and the NEC-LTR probe in the long terminal repeat gene allowed us to detect accurately the majority of HIV-1 subtypes of group M circulating in sub-Saharan Africa, including subtypes A, B, C, D, and G as well as circulating recombinant forms 02 and 11. The detection threshold of real-time PCR for HIV in cervicovaginal lavage samples was 5 copies per assay for both RNA and DNA; the intra- and interassay coefficients of variation of C T values were 1.30% and 0.69% (HIV-1 RNA) and 1.84% and 0.67% (HIV-1 DNA), respectively. Real-time PCR for HSV using primers and probe targeting the HSV DNA polymerase gene allowed both detection and quantification of HSV DNA and also differentiation between HSV-1 and HSV-2 genotypes. The detection threshold of real-time PCR for HSV was 5 copies per assay; the intra- and interassay coefficients of variation of C T values were 0.96% and 1.49%, respectively. Both manual and automated silica-based procedures were appropriate for combined extraction of HIV and HSV genomes from female genital secretions. Taken together, these findings indicate that real-time PCR may be used as a unique nucleic acid amplification procedure to detect and quantify HIV and HSV genomes in cervicovaginal secretions and thus to assess at reduced costs the genital shedding of both viruses in women included in intervention studies.

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.

Background/Aims : We herein focused on identifying biological factors possibly involved in non-parenteral transmission of hepatitis C virus (HCV), such as HCV excretion patterns and antibody-based immunity to the virus in saliva and/or cervicovaginal secretions (CVS). Methods : Paired blood, saliva and cervicovaginal lavage samples were obtained from HCV-RNA plasma-positive hemoglobin (Hb) antigen and HIV-seronegative, HCV-seropositive males ( n =13) and females ( n =21). HCV-specific antibodies were detected by ELISA in paired samples, and HCV-RNA was detected in cell-free and cell-associated body fluids. Results : Antibodies to E1 HCV surface glycoprotein of the IgG and IgA isotypes showed similar, but less pronounced, profiles as IgG and IgA to E2. HCV-specific IgG and IgA in mucosal fluids likely originated predominantly from the systemic compartment, because HCV-specific mucosal immunoglobulins involved primarily monomeric antibodies, including monomeric IgA, and because their specific activities for HCV antigens in corporeal fluids were similar to those in paired serum (Se). Viral shedding in saliva or CVS was restricted to cell-associated, non-replicating strand (+) HCV-RNA in 42% (12 out of 28) of saliva and in 19% (four out of 21) of cervicovaginal fluids. Conclusions : The association in body fluids of HCV-specific IgG, and to a lesser extent IgA, directed to E1/E2 surface glycoproteins (which may block critical steps of virus–cell interactions), of undetectable free viral RNA, and of occasional non-replicating cell-associated HCV, suggests a resulting poor infectivity of saliva or cervicovaginal fluid in chronically HCV-infected individuals. Taken together, these observations provide the basis for the low risk of non-parenteral transmission of HCV infection.

Antibodies to human immunodeficiency virus (HIV) of the IgA, IgG, and IgM isotypes and high levels of the HIV suppressive beta-chemokine RANTES (regulated on activation, normally T cell expressed and secreted) were found in the cervicovaginal secretions (CVSs) of 7.5% of 342 multiply and repeatedly exposed African HIV-seronegative female sex workers. The antibodies are part of a local compartmentalized secretory immune response to HIV, since they are present in vaginal fluids that are free of contaminating semen. Cervicovaginal antibodies showed a reproducible pattern of reactivity restricted to gp160 and p24. Locally produced anti-env antibodies exhibit reactivity toward the neutralizing ELDKWA epitope of gp41. Study results show that antibodies purified from CVSs block the transcytosis of cell-associated HIV through a tight epithelial monolayer in vitro. These findings suggest that genital resistance to HIV may involve HIV-specific cervicovaginal antibody responses in a minority of highly exposed HIV-seronegative women in association with other protecting factors, such as local production of HIV-suppressive chemokines.

Progressive Multifocal Leukoencephalopathy (PML) is a severe and fatal demyelinating disease that occurs especially in HIV-infected patients. It has been suggested that JC virus (JCV) migrates in peripheral blood leukocytes from the kidney to the central nervous system where it initiates demyelination. To investigate the physiopathological role of the peripheral blood virus in the development of PML, the prevalence of JCV infection and the levels of JCV DNA load were evaluated in peripheral blood leukocytes or mononuclear cells of 10 AIDS patients at the time of onset of PML symptoms, and in 150 non-PML HIV-1-infected patients using a semiquantitative PCR and ELISA-hybridization assay. In PML-AIDS patients, 60% (6/10) were positive for JCV-DNA detection in peripheral blood cells compared with 26% (13/50) and 18% (18/100) positive for non-PML HIV-infected control patients with CD4+ T lymphocyte counts below and above 200.106 /l, respectively (60 vs. 26%, P = 0.06; 60 vs. 18%; P = 0.007). The prevalence of JCV infection in the peripheral blood cells taken from controls appeared to be independent of the CDC stage of infection and CD4+ T lymphocyte counts. The predictive positive value of a positive JCV DNA PCR in peripheral blood cells for the diagnosis of PML in an HIV-infected patient was 16% whereas the predictive negative value was 96%. The levels of circulating JCV DNA load, ranging from 1.69 to 2.53 log of copies per 106 cells, did not differ between patients at time of PML symptoms onset and controls, and appeared to be independent of the clinical and the biological status in control patients. The findings do not indicate any significant JCV genomic replication activity in peripheral blood cells at the onset of PML disease, and suggest that JCV replication markers in the systemic compartment would not be valuable for predicting the development of PML in AIDS patients. J. Med. Virol. 66:1–7, 2002. © 2002 Wiley-Liss, Inc.

Two commercially available hypersensitive assays for human immunodeficiency virus type 1 (HIV-1) RNA quantitation, AMPLICOR HIV-1 Monitor Test 1.5 and Quantiplex HIV RNA 3.0, were compared to detect and quantify HIV-1 RNA in the cell-free fraction of cervicovaginal secretions collected by vaginal washing. Three panel specimens were used: pooled cervicovaginal secretions spiked with HIV-1 subtype A or HIV-1 subtype B and cervicovaginal lavages from HIV-positive and HIV-negative women. Compared to the AMPLICOR HIV-1 Monitor Test 1.5 assay, the Quantiplex HIV-1 3.0 assay yielded higher estimates of HIV-1 RNA concentrations in several tested samples spiked with HIV-1 RNA subtype A, as well as subtype B, particularly samples containing low amounts of HIV-1 RNA. The sensitivity and specificity of the AMPLICOR HIV-1 Monitor Test 1.5 assay were 93 and 100%, respectively; the sensitivity and specificity of the Quantiplex HIV RNA 3.0 assay were 97 and 50%, respectively. In conclusion, in quantifying HIV-1 RNA in cervicovaginal secretions, the Quantiplex HIV RNA 3.0 may lack specificity, and the AMPLICOR HIV-1 Monitor Test 1.5 assay, although highly specific, may lack sensitivity.

Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development.

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.

The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.

Background . Surgeons face the risk of patient-to-physician transmission of blood-borne viruses. This risk is related to the seroprevalence of the viruses in the patient population. Methods . The seroprevalence of the human immunodeficiency virus, hepatitis B virus, and hepatitis C virus were determined in cardiovascular patients at Hopital Broussais in Paris, France, over a 5-year period (1994 to 1998). Results . Hepatitis C virus is the most prevalent virus in the patient population, whereas human immunodeficiency virus is the least frequent. The seroprevalence of hepatitis C virus and human immunodeficiency virus has decreased over time, whereas hepatitis B virus has remained constant. We apply the seroprevalence data to a mathematical model to estimate the occupational risk of seroconversion faced by surgeons over the length of their career. Our results show that the principal risk faced by the surgeon arises from hepatitis B virus and hepatitis C virus. The decreasing seroprevalence of the hepatitis C virus has resulted in a decrease in the occupational risk. Conclusions . The probability of becoming infected with a blood-borne virus over the career of the surgeon is notable. The greatest occupational risk to the surgeon is from the hepatitis viruses and not HIV.

Using commercially available herpes simplex virus (HSV) type-specific serological diagnostic tests, HSV type 2 (HSV-2) antibody prevalence was assessed in two parallel prospective studies including 534 human immunodeficiency virus type 1 (HIV-1)-infected outpatients living in two areas of northern France. In the first cohort of 434 subjects, 223 (51%) individuals demonstrated a positive HSV-2 serological status while 66 (66%) of 100 subjects in the second cohort were seropositive for HSV-2 (51 versus 66%; P = 0.08). Among the 223 HSV-2-seropositive subjects identified in the first study cohort, only 22 (10%) had suffered from recurrent anogenital lesions during the past 12 months while 154 (69%) had no clinical history of herpesvirus infection. Our findings demonstrate high proportions of subclinical and undiagnosed HSV-2 infection in HIV-1-infected individuals and suggest that HSV type-specific serological testing in the French HIV-1-infected subpopulation could be an efficient strategy to diagnose clinically asymptomatic HSV-2 infections.

Paired sera, saliva and cervicovaginal secretions from 17 HTLV-I-infected women (19-75 yr) were tested for total IgA and IgG, for IgA and IgG to the immunodominant region gp46/175-Pro-199, for serum IgG to the neutralizing domains gp46/ 190-Pro-199 and gp46/190-Ser-199, or for tax-rex proviral HTLV-DNA. Serum antibodies to gp46/ 175-Pro-199 were detected more frequently in the IgG (13/17) than in the IgA (5/17) isotypes. The majority (8/12) of anti-gp46/175-Pro-199-positive sera reacted also to gp46/190-Pro-199 or to gp46/ 190-Ser-199, demonstrating their neutralizing properties. In saliva, antibodies to gp46/175-Pro-199 were not generally detected. In cervicovaginal secretions, IgG to gp46/175-Pro-199, but not IgA, were detected in 6/15 (40%) patients. The mean specific activity of IgG to gp46/175-Pro-199 showed a trend to be higher in cervicovaginal secretions (218 +/- 109) than in sera (14 +/- 4). Furthermore, in all patients with cervicovaginal IgG to gp46/175-Pro-199, the cervicogaginal/serum ratio (19 +/- 6) of anti-gp46 IgG specific activities were markedly above 1. HTLV-DNA was detected in 4/17 salivas, and in 3/15 cervicovaginal secretions, all from patients demonstrating cervicovaginal synthesis of IgG to gp46/175-Pro-199. In conclusion, IgG to gp46/175-Pro-199 in cervicovaginal secretions, when present, appear to be produced primarily locally because of local HTLV-I excretion. Since anti-gp46/175-Pro-199 antibodies usually support reactivities to neutralizing domains, their presence could be relevant for limiting HTLV-I transmission via cervicovaginal secretions.

Paired sera and cervicovaginal secretions (CVS) from 11 HIV-1- and 11 HIV-2-infected women, all clinically asymptomatic (CDC A1 and A2 categories), were analyzed for total IgG, IgA, albumin (HSA), IgG, and IgA antibodies toenvencoded surface glycoproteins of HIV-1 (gp160) and of HIV-2 (gp105), by comparison to 15 age-matched healthy controls. Secretion rates of IgG and IgA into CVS were evaluated by calculation of their relative coefficients of excretion (RCE) by reference to HSA. Cervicovaginal production of anti-HIV antibodies was evaluated by comparison between specific antibody activities of IgG and of IgA to HIV in CVS and in sera. In HIV-1-infected women, total IgG and IgA in CVS were, respectively, 6- and 4-fold increased, whereas the secretion rate of total IgG was 2.1-fold increased and that of total IgA was 2.5-fold reduced. In contrast, total IgG and IgA as well as their secretion rates were normal in HIV-2-infected women. In HIV-1- but not in HIV-2-infected women, HSA levels in cervicovaginal washings were twofold increased, demonstrating alteration of the mucosal barrier in HIV-1 infection. In HIV-1-infected patients, IgG and IgA to gpl60 were detected in all sera and CVS. In HIV-2-infected patients, IgG to gp105 was detected in all sera and CVS, whereas IgA to gp105 could be detected in only half of sera and one-third of CVS. Cross-reactivity by IgG and/or IgA to HIV-1 or HIV-2 against the surface glycoprotein of the other HIV type was observed in sera as well as in CVS, and more frequently in HIV-2- than in HIV-1-infected women. Finally, the mean specific activities of IgG and of IgA to gp160 or gp105 were higher in CVS than in sera, evidencing a possible local synthesis of both isotypes in HIV-1 as well as in HIV-2 infections. As early as the asymptomatic stages, HIV-1 affects the cervicovaginal mucosa more than HIV-2 does, suggesting higher viral replication within the female genital tract in HIV-1 infection than in HIV-2 infection.

Asymptomatic genital shedding of herpes simplex virus type 2 (HSV-2) DNA was evidenced by real-time PCR in 25 (13.2%) of 188 cervicovaginal lavage samples and in only 13 (6.9%) paired cervicovaginal samples from 188 HSV-2-seropositive, nonpregnant childbearing-aged human immunodeficiency virus-seronegative women living in Gabon. These observations demonstrate that cervicovaginal washing is more suitable than endocervicovaginal swabbing for detecting and quantifying HSV-2 DNA by PCR in female genital secretions.

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.

Background The female genital tract constitutes a reservoir for HIV providing active production of both cell-free HIV RNA and cell-associated DNA within the cervicovaginal secretions. The objective of this study was to prospectively assess residual HIV-1 RNA and HIV-1 DNA production in the genital tract reservoir of women initiating HAART over an 18-month period. Methods Paired blood and cervicovaginal lavage samples were collected at inclusion and 1, 6, 12 and 18 months after HAART initiation, in 23 women in first-line HAART and six women in virological failure, for measurement of HIV-1 RNA and HIV-1 DNA shedding and/or drug concentrations. Results A dramatic decrease of HIV-1 RNA and HIV-1 DNA occurred in both blood and cervicovaginal samples over the first 6 months on HAART, followed by a shelf up to 18 months, independently of the drugs’ genital pharmacokinetics. While cervicovaginal HIV-1 RNA became undetectable in >90% of women from 6 months on HAART, genital HIV-1 DNA remained frequently detectable (27–50%). Nearly 40% of women with sustained undetectable plasma HIV-1 RNA after 6–18 months on HAART harboured transient HIV-1 RNA (15% of women) or HIV-1 DNA (31% of women) in their genital secretions. Conclusions Low-level cervicovaginal HIV-1 shedding is frequently evidenced in HAART-treated women with transient HIV-1 RNA and persistent HIV-1 DNA despite a systemic control of viral replication, resulting in possible residual genital infectivity.

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.

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. 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. 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. (authors)

Using ultrasensitive polymerase chain reaction–based techniques we assessed levels of cell-free and cellassociated human immunodeficiency virus (HIV)–1 in paired blood and genital samples of 30 clinically asymptomatic treatment-naive women. Levels of HIV-1 RNA in cervicovaginal-lavage samples were positively correlated with those in plasma samples (r=.50; P=.008) whereas levels of HIV-1 DNA in genital samples were loosely correlated with those in blood samples (r=.31; P=.041). In plasma of peripheral blood levels of HIV-1 DNA were positively correlated with those of HIV-1 RNA (r=.64; P < .001) whereas no correlation between HIV-1 DNA and HIV-1 RNA was evident in genital secretions. Our results indicate that levels of HIV-1 RNA and HIV-1 DNA are unrelated in the genital tracts of treatment-naive women and suggest that the level of genital HIV-1 RNA is influenced by systemic viral replication—in contrast to genital HIV-1 provirus which may be influenced as well by local cofactors triggering the migration of HIV-infected cells originating from the cervicovaginal submucosa. These features may be relevant for an understanding of HIV-1 transmission in heterosexual individuals. (authors)

Human immunodeficiency virus type 1 (HIV-1) RNA was detected by means of ultrasensitive reverse transcription-PCR assay of 19 cervicovaginal lavage, 21 cervical mucus, 18 vaginal wall, and 17 vaginal fornix paired samples from 25 asymptomatic HIV-1-infected women (76, 84, 72, and 68%, respectively; P > 0.5). Levels of HIV-1 RNA in cervicovaginal wash samples were highly correlated with those in paired endocervical mucus samples ( r = 0.71; P = 0.0006), indicating that cervicovaginal washing and endocervical swabbing are equivalent collection procedures.

Plasma levels of proinflammatory cytokines, cytokine inhibitors, and the beta chemokines RANTES, macrophage inhibitory protein (MIP)-1alpha, and monocyte chemoattractant protein (MCP)-1 were studied in relationship with virus load in 40 patients exhibiting plasma levels of HIV RNA ranging between undetectable and levels10(6) copies/mL. Mean plasma levels of MCP-1 were increased in patients with high virus load compared with HIV-seropositive subjects with undetectable plasma viral RNA and healthy controls. MCP-1 levels were directly correlated with plasma levels of HIV RNA. No correlation was observed between virus load and plasma concentrations of MIP-1alpha and RANTES. The results suggest that low rates of viral replication in vivo are not dependent on increased production of the suppressive chemokines RANTES and MIP-1alpha. Since MCP-1 upregulates viral replication in vitro, the results may suggest a role for MCP-1 in triggering viral replication in HIV disease.