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Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV.

OBJECTIVES: To determine the rates of, and risk factors for, mother-to-child transmission (MCT) of HIV-1 and HIV-2 infection in The Gambia. DESIGN: A blinded, prospective, community-based cohort study of 29.549 pregnant women attending the eight largest antenatal clinics in The Gambia. METHODS: Women were tested for HIV-1 and HIV-2 infection. Infected subjects and a group of HIV-seronegative women were followed with their babies until 18 months after delivery. Maternal CD4 cell count percentages were measured before and 18 months after delivery, and the antenatal plasma viral load was determined. Babies were tested for HIV by the polymerase chain reaction and/or serology at 2, 9 and 18 months of age. RESULTS: The study enrolled 144 women positive for HIV-1 and 294 for HIV-2 plus 565 seronegative pregnant women: the mean antenatal percentage CD4 cell counts of 96 HIV-1-positive, 223 HIV-2-positive and 125 HIV-seronegative mothers were 31% [95% confidence interval (CI) 28-33], 41% (95% CI 39-42) and 47% (95% CI 45-49), respectively. The geometric mean antenatal plasma viral load of 94 HIV-1-infected women was 15,100 copies x 10(3) ml (95% CI 10,400-19,000) which was much higher than that of 60 randomly selected HIV-2-infected women, which was 410 copies x 10(3) ml (95% CI 150-910) (P < 0.001). The estimated transmission rate of HIV-1 was 24.4% (95% CI 14.6-33.9) and that of HIV-2 was 4.0% (95% CI 1.9-7.4). Five of 17 HIV-1-positive and three of eight HIV-2-positive babies were infected after 2 months of age. Birth in the rainy season [odds ratio (OR) 2.9; 95% CI 1.2-7.2], a low postnatal CD4 cell percentage (OR for a 10% fall 2.4; 95% CI 1.1-5.1) and a high maternal plasma viral load (OR for a 10-fold increase 2.9; 95% CI 1.1-7.8) were risk factors for transmission that applied equally to both viruses. CONCLUSION: Low maternal HIV-2 RNA levels, which on average are 37-fold less than in HIV-1 infection, relate to the low MCT rate of HIV-2.

CD4 Lymphocyte Count↗

Chlamydial and gonococcal cervicitis in HIV-seropositive and HIV-seronegative pregnant women in Bangkok: prevalence, risk factors, and relation to perinatal HIV transmission.

OBJECTIVES: To determine the prevalence and risk factors associated with cervicitis caused by Chlamydia trachomatis and Neisseria gonorrhoeae in human immunodeficiency virus (HIV) type 1-seropositive and HIV-seronegative pregnant women in Bangkok, and the relation to perinatal HIV transmission. METHODS: As part of a multicenter perinatal HIV transmission study in an antenatal population with 2% HIV seroprevalence, endocervical swabs obtained at mid-pregnancy from a consecutive sample of 222 HIV-seropositive and 219 HIV-seronegative pregnant women at two large hospitals in Bangkok were tested for the presence of C. trachomatis and N. gonorrhoeae by DNA hybridization probe (Gen-Probe). Clinical risk factors and DNA probe results were analyzed in relation to the women's and newborns' HIV infection status. RESULTS: The prevalence of C. trachomatis was 16.2% in HIV-seropositive pregnant women and 9.1% in HIV-seronegative pregnant women (P = 0.03). The prevalence of N. gonorrhoeae was 2.7% in HIV-seropositive pregnant women and 1.4% in HIV-seronegative pregnant women (P = 0.5). The overall population prevalence estimate was 9.2% for C. trachomatis and 1.4% for N. gonorrhoeae. Women with gonococcal infection were more likely to be positive for C. trachomatis (RR(MH) = 5.2, P < 0.01). Young age (<21 years) and primigravid status were associated with C. trachomatis infection among HIV-seropositive women; history of multiple sex partners (>1) were associated with C. trachomatis infection among HIV-seronegative women. For HIV-seropositive women, primigravida status also was associated with C. trachomatis infection. The perinatal HIV transmission rates were similar for those with and without C. trachomatis (24.1% and 23.2%, P = 0.9) and among those with and without N. gonorrhoeae (20% and 23.5%, P = 1.0). CONCLUSIONS: Among pregnant women in Bangkok, C. trachomatis infection was considerably more common than N. gonorrhoeae infection and was associated with HIV infection, young age and first pregnancy (HIV-seropositive women), and multiple partners (HIV-seronegative women). Our data do not suggest an association between perinatal HIV transmission and maternal C. trachomatis or N. gonorrhoeae infection identified and treated during pregnancy. The high prevalence of C. trachomatis found using a test not readily available in Thailand emphasizes the need for improved, inexpensive ways to screen for and diagnose these sexually transmitted infections in developing countries.

Adult↗

Diagnostic challenges for rapid human immunodeficiency virus assays. Performance using HIV-1 group O, HIV-1 group M, and HIV-2 samples.

OBJECTIVE: We sought to determine the ability of seven rapid assays for human immunodeficiency virus (HIV) to detect antibodies in a panel of sera from individuals infected with different types and groups of HIV. STUDY DESIGN/METHODS: Sixty-eight well-characterized samples, including HIV-1 group O (24), several HIV-1 group M clades (21), HIV-1/2 (10), HIV-2 (10), and samples with indeterminate results (3), were tested by the following rapid HIV assays: HIV-Spot, HIVCHEK System 3, A/Q Rapid HIV, Genie II HIV-1/HIV-2, Quix HIV-1-2-O, ImmunoComb II HIV-1+2 BiSpot, and the Serodia HIV-1+2. RESULTS: All tests successfully detected the HIV-1 group M clades and the HIV-1/2-positive samples. Of the HIV-2 stand-alone samples, four tests missed the same sample, and three tests missed another sample. Of the HIV-1 group O samples, four samples were missed by at least one test, and another sample was missed by three tests. The sensitivity of the seven rapid assays in detecting each group of sera was between 83% and 100%, with only one test having a sensitivity of 100% for all groups of sera. Three samples proved to be problematic because they were misclassified by more than one assay. CONCLUSIONS: The performance of rapid HIV assays is variable when testing sera from individuals infected with HIV-1 group O and HIV-2.

Evaluation Studies as Topic↗

GACPAT HIV 1 + 2: a simple, inexpensive assay to screen for, and discriminate between, anti-HIV 1 and anti-HIV 2.

A simple and cheap assay suitable for screening for anti-HIV 1 and anti-HIV 2 and discriminating between them was evaluated. In it specimens are incubated in U-bottomed microplate wells coated with anti-human IgG for 30 min at room temperature. After washing, 100 microliters of a 1 in 50 dilution of HIV 1-coated gelatin particles (Serodia-HIV 1/2, Fujirebio) are added. Settling patterns are read on the second day: A positive reaction is indicated by adherence of the particles and a negative by a button. The HIV 1 particles are then washed away and HIV 2 particles added. Anti-HIV 2 reaction patterns are read on the third day. To assess the performance of the modified "GACPAT HIV 1 + 2" assay a panel of 1,621 serum/plasma specimens was used. It comprised validated anti-HIV 1 positive (n = 220), anti-HIV 2 positive (n = 214), dual anti-HIV 1/anti-HIV 2 positive (n = 11), and anti-HIV negative (n = 1,176) serum/plasma specimens. All 434 specimens that contained anti-HIV 1 or anti-HIV 2 reacted positively with the homologous particles. The 11 dually positive specimens reacted positively with both HIV 1 and HIV 2 particles. Five (2.3%) anti-HIV 1 and five (2.3%) anti-HIV 2 positive specimens gave positive reactions with both particle types, but none of the five cross-reactive anti-HIV 2 specimens were dually reactive when the order of particle addition was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

A study of seroprevalence of HIV-1 and HIV-2 in six provinces of People's Republic of Angola: clues to the spread of HIV infection.

A seroepidemiological study was carried out to determine the distribution of the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) in the People's Republic of Angola, where HIV-2 existence was previously unknown and HIV-1 seropositivity was only reported to be present in Luanda and Cabinda. A total of 1,695 serum samples were obtained from healthy persons (control group) and from a group of patients in the provinces of Zaire (13), Lunda-Norte (L.N.) (749), Luanda (556), Huambo (154), Kuando-Kubango (K.-K.) (49), and Namibe (119). All samples were tested for HIV-1 and HIV-2 antibodies by enzyme-linked immunosorbent assay and an indirect immunofluorescence assay using MOLT-T4 cells. Positive samples were confirmed by the Western-blot technique. Sera giving cross reactivity at the level of HIV-1 and HIV-2 large glycoproteins were further tested by radioimmunoprecipitation assay and by reactivity against a peptide corresponding to the dominant epitope of the transmembrane protein. The overall seroprevalance was 14.2%, with significantly higher values in the patient group [19.4% (HIV-1 = 8.8%; HIV-2 = 8.4%; HIV-1 + HIV-2 = 2.2%)] than the control group [9.3% (HIV-1 = 3.3%; HIV-2 = 5.3%; HIV-1 + HIV-2 = 0.7%)]. HIV-2 as well as HIV-1 infection is actually present in Angola in all studied provinces. Higher seroprevalence was seen in the provinces of Zaire, Lunda Norte, and Huambo. People displacements, mainly as a consequence of the war, certainly play an important role in spreading HIV infection from the northern frontier areas of the country to the central and southern regions.

Adolescent↗

Strongly enhanced sensitivity of a direct anti-HIV-1/-2 assay in seroconversion by incorporation of HIV p24 ag detection: a new generation vironostika HIV Uni-Form II.

The clinical sensitivity of the current anti-HIV assays is based for an important part on their reactivity with seroconversion panels. The most sensitive assay closes the seroconversion window as much as possible, thereby reducing the risk of transmitting false negative donations obtained from individuals infected recently. Because of the absence of anti-HIV antibodies during the early phase of infection, the seroconversion window can be narrowed partially by detection of HIV p24 Ag. To achieve this, the highest affinity anti-p24 binding antibodies were selected with BlAcore and applied in a direct assay format. To achieve optimal conditions for the anti-HIV part of the assay the HIV specific antigens viral HIV-1 gp160, HIV-2 gp36 and HIV-1 group O gp41 peptides were used. These antigens and antibodies were applied for microELISA coating as well as in the conjugate pearl, which is present in the well of the microELISA plate. The (analytical) anti-HIV-1/-2 and anti-HIV-1 group O sensitivity of this new assay, Vironostika HIV Uni-Form II Ag/Ab, is at least at the level of the current Vironostika HIV Uni-Form II plus O. When compared to the Vironostika HIV Uni-Form II plus O, the seroconversion window is narrowed by 1-2 weeks due to the incorporation of HIV p24 Ag detection. The level of reactivity of the anti-HIV and HIV Ag detection part can be improved by about a factor 2 by applying continuous shaking during sample incubation. Initial studies suggested that the specificity of the assay is identical to that of the Vironostika HIV Uni-Form II plus O, namely > 99.9%. Monitoring of proper execution of the assay handling steps was facilitated by implementing a purple dye in the conjugate pearl. Colourless specimen diluent changes into a green fluid upon dissolving of the conjugate pearl and turns subsequently into blue/purple upon sample addition. These visual changes can also be determined by spectrophotometric measurement at 620 nm.

Enzyme-Linked Immunosorbent Assay↗

T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents: retention of naive T lymphocytes in HIV-infected adolescents. The Adolescent Medicine HIV/AIDS Research Network.

BACKGROUND: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. OBJECTIVE: To assess lymphocyte subsets in HIV-infected and high-risk HIV-negative adolescents. DESIGN: The Reaching for Excellence in Adolescent Care and Health Project of the Adolescent Medicine HIV/AIDS Research Network recruits a cohort of HIV-infected and high-risk HIV-uninfected adolescents, aged 13 to 18 years 364 days, into a study of biomedical and behavioral features of HIV infection as seen in the context of full availability of primary care and HIV-related consultative services. Lymphocyte phenotypes were determined using standard 3-color flow cytometry. SETTING: The Reaching for Excellence in Adolescent Care and Health Project is carried out at 16 clinical sites in 14 urban areas. PARTICIPANTS: T-lymphocyte subsets are reported in 192 HIV-positive and 78 HIV-negative youths. RESULTS: For HIV-positive subjects, the total CD4+ cell count and the percentage of CD4+ cells are decreased when compared with those of the HIV-negative controls (P<.001). The reduction in total CD4+ cells reflects a loss of naive, and memory, CD4+ cells compared with HIV-negative youths. Human immunodeficiency virus-infected adolescents, many of whom have been infected recently (ie, those with CD4+ cell counts > or =0.500 x 10(9)/L [500/microL]), have a significant increase in naive CD8+ cells compared with HIV-negative youths (P<.01). There also is a significant increase in memory CD8+ cells at all strata of total CD4+ cells compared with HIV-negative youths (P<.01). The increase in naive CD8+ cells in those subjects with CD4+ cell counts of 0.500 x 10(9)/L or greater is a unique finding in this cohort. CONCLUSIONS: This study demonstrates high levels of naive CD8+ cells in response to HIV infection in adolescents with CD4+ cell counts of 0.500 X 10(9)/L or greater. The presence of high levels of naive CD8+ cells suggests functioning thymic tissue in some adolescents infected with HIV. Furthermore, the normal level of naive CD4+ cells in adolescents with CD4+ levels of 0.500 x 10(9)/L or greater provides additional support for the concept of a more robust immune system in HIV-infected adolescents compared with HIV-infected adults. These observations suggest that the immune system of HIV-infected adolescents may be capable of better responses to neoantigens and cytotoxic T-lymphocyte responses to HIV than the immune system of infected children or adults. Human immunodeficiency virus-infected adolescents may have an immune system that is capable of reconstitution following highly active antiretroviral therapy.

Adolescent↗

Mortality of HIV-1, HIV-2 and HIV-1/HIV-2 dually infected patients in a clinic-based cohort in The Gambia.

OBJECTIVE: To assess and compare the mortality rates of patients with HIV-1, HIV-2 or both infections (HIV-D) in the same population. DESIGN: Clinic-based cohort study. METHODS: HIV-seropositive patients aged 15 years and older who attended the Medical Research Council clinics in Fajara between May 1986 and September 1997 were recruited. Clinical assessment using the Karnofsky score, CDC cell staging, WHO staging, and CD4 cell counts was performed at baseline. Patients attended clinic every 3 months; if they did not attend, they were visited at home by field workers to ascertain survival status. No patient was on antiretroviral therapy during the study period. RESULTS: Data from 1519 HIV-positive adult patients were analysed. A total of 746 patients had HIV-1, 666 HIV-2, and 107 patients had HIV-D. A total of 828 patients (55%) died, and 161 (11%) were lost to follow-up. The median follow-up was 12 months (range 0-128). CD4 cell counts were available for 894 patients. Compared with HIV-1, the adjusted hazards ratio for mortality in the CD4 cell count category 500 cells/microl or greater was 0.50 for HIV-2 (95% CI 0.28-0.88) and 1.27 (95% CI 0.51-3.7) for HIV-D. Among those with CD4 cell counts less than 500 cells/microl the mortality rates in HIV-2 and HIV-D were similar to those in HIV-1. DISCUSSION: HIV-2-infected patients with CD4 cell counts of 500 cells/microl and greater had a significantly lower mortality rate than HIV-1-infected patients. HIV-2-infected patients with advanced disease had the same poor prognosis as patients with HIV-1. Dually infected patients had mortality rates similar to HIV-1.

Adolescent↗

Human immunodeficiency virus (HIV) type 2-mediated inhibition of HIV type 1: a new approach to gene therapy of HIV-infection.

Human immunodeficiency virus (HIV) type 2, the second AIDS-associated human retrovirus, differs from HIV-1 in its natural history, infectivity, and pathogenicity, as well as in details of its genomic structure and molecular behavior. We report here that HIV-2 inhibits the replication of HIV-1 at the molecular level. This inhibition was selective, dose-dependent, and nonreciprocal. The closely related simian immunodeficiency provirus also inhibited HIV-1. The selectivity of inhibition was shown by the observation that HIV-2 did not significantly downmodulate the expression of the unrelated murine leukemia virus; neither did the murine leukemia virus markedly affect HIV-1 or HIV-2 expression. Moreover, while HIV-2 potently inhibited HIV-1, the reverse did not happen, thus identifying yet another and remarkable difference between HIV-1 and HIV-2. Mutational analysis of the HIV-2 genome suggested that the inhibition follows a complex pathway, possibly involving multiple genes and redundant mechanisms. Introduction of inactivating mutations into the structural and regulatory/accessory genes did not render the HIV-2 provirus ineffective. Some of the HIV-2 gene defects, such as that of tat and rev genes, were phenotypically transcomplemented by HIV-1. The HIV-2 proviruses with deletions in the putative packaging signal and defective for virus replication were effective in inducing the suppressive phenotype. Though the exact mechanism remains to be defined, the inhibition appeared to be mainly due to an intracellular molecular event because it could not be explained solely on the basis of cell surface receptor mediated interference. The results support the notion that the inhibition likely occurred at the level of viral RNA, possibly involving competition between viral RNAs for some transcriptional factor essential for virus replication. Induction of a cytokine is another possibility. These findings might be relevant to the clinical-epidemiological data suggesting that infection with HIV-2 may offer some protection against HIV-1 infection.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau.

Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.

Adolescent↗

Cervical intraepithelial neoplasia and human papillomavirus infection among Senegalese women seropositive for HIV-1 or HIV-2 or seronegative for HIV.

Studies in various regions of the world have shown that women infected with HIV-1 are at increased risk for cervical human papillomavirus (HPV) infection as well as for cervical cancer precursor lesions. HIV infection and cervical cancer are both widespread in West Africa, but little is known about the relationship between HPV and HIV-2, which is the predominant type of HIV in the general population of many West African countries. To address this issue, we collected cervical samples for cytology and HPV analysis from 93 women presenting to the University of Dakar Infectious Disease Service (18 women with HIV-1 infection, 17 with HIV-2 infection, and 58 HIV seronegative controls). Compared to those without HIV infection, HIV seropositive women were 13.1 (95% CI = 2.4, 128) and 11.0 (95% CI = 3.5, 35.8) times more likely to have HPV detected using Southern transfer hybridization (STH) and the polymerase chain reaction (PCR) respectively. Detection of high and intermediate risk HPV types were significantly associated with HIV-1 and HIV-2 infection. Among HPV positive women, those with, as compared to those without HIV infection were more likely to harbour high risk HPV types (OR = 9.2, 95% CI = 0.97, 433). HIV-1 and HIV-2 seropositive women were 23.3 (95% CI = 2.9, 209) and 9.3 (95% CI = 1.1, 79) times more likely to have cytological diagnosis of dysplasia, respectively, than were HIV seronegative women. Biopsy-proven CIN 3 was found in one woman with HIV-1 and invasive cancer was found in one woman with HIV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗

Multicenter study of the LCx HIV RNA quantitative assay--a new competitive reverse transcriptase-PCR which targets pol genomic region of HIV-1 for the measurement of type B, non-type B and group O HIV-1 RNA.

Performance characteristics of the Abbott LCx HIV RNA Quantitative Assay (LCx HIV) were established in a multicenter study comparing it with the manual (Amplicor v1.5) and automated (Cobas) ultra-sensitive Roche Amplicor HIV-1 Monitor v1.5, the Bayer Quantiplex HIV RNA 3.0 (bDNA v3.0), and the Organon NucliSens HIV QT 2.0 (NucliSens). Within-run precision of LCx HIV assessed in clinical specimens was SD log10 0.210 at approximately 50 copies/ml, and log10 0.133 at approximately 400 copies/ml. Total precision in a reconstituted type B HIV-1 RNA panel was SD log10 0.380 at 100 copies/ml, and SD log10 0.180 at 1000 copies/ml. Type B HIV-1 RNA sensitivity (1 ml input) assessed at a 50%, 75% and 95% detection rate ranged from 29 to 41, 54 to 75 and 94 to 176 copies/ml, respectively. Overall specificity in HIV seronegative individuals was 99.78%. Linear regression indicated close assay correlations and agreements for measurement of type B HIV-1 RNA. Pearson's correlations and (Log10LCx=aLog10x + b) linear regressions were 0.91 (y=0.892 Log10Amplicor + 0.595), 0.93 (y=0.827 Log10Cobas + 0.969), 0.93 (y=0.951 Log10bDNA + 0.550), and 0.79 (y=0.834 Log10NucliSens + 0.911). LCx HIV was least affected by the genetic variability of HIV-1. LCx HIV detected 99% of non-type B HIV-1 group M samples (subtypes A-G), Amplicor v1.5 detected 96%, and bDNA v3.0 detected 99%. The assays detected 10/11, 1/11 and 8/11, respectively of the HIV-1 group O samples. LCx HIV vs. Amplicor/bDNA Spearman's rank correlations for quantification of non-type B HIV-1 RNA were 0.76/0.84 (A), 0.93/0.93 (C), 0.73/0.99 (D), 0.86/0.98 (E), and 0.40/0.83 (group O). LCx HIV assays consistently detect and quantify type B, non-type B and group O HIV-1 RNA.

Acquired Immunodeficiency Syndrome↗

Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2.

BACKGROUND: The HIV-1 epidemic in West Africa is characterized by a slower rise than that in Eastern and Southern Africa. The HIV-2 epidemic in West Africa may be declining, but few long-term data exist. METHODS: In a research clinic in The Gambia, HIV-1 and HIV-2 prevalence trends among all new patients being tested for HIV were examined over a 16 year period (1988 till 2003). In newly diagnosed patients a baseline CD4 count was done. RESULTS: An HIV test was done in 23 363 patients aged 15 years or older. The prevalence of HIV-1 was 4.2% in 1988-91 and rose to 17.5% in 2001-03 (P < 0.0001, chi(2)-test for trend). The prevalence of HIV-2 was 7.0% in 1988-91 and declined to 4.0% in 2001-03 (P < 0.0001). HIV-1 prevalence increased and HIV-2 prevalence decreased with time in logistic regression models adjusting for age, sex, and indication for test (P < 0.0001). Baseline CD4 counts were available for 65% of patients. The median CD4 count was 215 cells/mm3 [interquartile range (IQR) 72-424] for HIV-1, and 274 (IQR 100-549) for HIV-2 infected patients. There was no marked trend of rise or decline in baseline CD4 count in either HIV-1 or HIV-2 infected patients over the study period. Forty-five per cent of newly diagnosed HIV patients had a CD4 count <200 cells/mm3. CONCLUSIONS: These data suggest that HIV-1 prevalence is rising in The Gambia, and that HIV-2 is declining. HIV patients in The Gambia present late and almost half of patients would qualify for anti-retroviral treatment at their first visit.

Adolescent↗

Knowledge, attitudes and behaviour among HIV-positive and HIV-negative clients of a confidential HIV counselling and testing centre in Thailand.

OBJECTIVE: To describe the clients, operation and impact of an Asian public HIV counselling and testing centre. DESIGN AND SETTING: Analysis of samples from clients attending the Thai Red Cross Anonymous Clinic (TRC-AC) in Bangkok, Thailand in 1993. SUBJECTS: HIV-positive and HIV-negative consecutive clients (250 of each). MAIN OUTCOME MEASURES: HIV seroprevalence rates, knowledge, attitudes and behaviour. RESULTS: Overall HIV-1 prevalence was 16%; 13% in men and 24% in women. Reasons for requesting an HIV test were high-risk behaviour (21%), feeling unwell (20%), checking a previous HIV test result (18%), a planned marriage or new relationship (10%), and planning a baby (5%). Heterosexual risk behaviour was reported by 85% of clients, while in each case only 1% reported male homosexual or intravenous drug use risk behaviour. Factors associated with HIV infection on univariate analysis included a history of sexually transmitted disease, not using condoms, a low level of education and salary, and being female. Knowledge about HIV transmission risks and AIDS prevention measures was good, and most clients expressed a caring attitude towards people with HIV and AIDS. A former negative HIV test result was associated with higher levels of condom use, and most clients expressed the intention to reduce their HIV risk behaviour in response to a positive or negative HIV test result (more so if positive). CONCLUSIONS: Our study demonstrates the demand for and the feasibility of confidential HIV counseling and testing services in Thailand and illustrates the value of these services in achieving behaviour changes. Such services should be considered as an additional approach for reducing HIV transmission in Asia, especially in areas with high HIV seroprevalence rates.

Adult↗

Does the recent increase in HIV diagnoses among men who have sex with men in the UK reflect a rise in HIV incidence or increased uptake of HIV testing?

OBJECTIVES: To determine whether the increase in HIV diagnoses since 1997 among men who have sex with men (MSM) in the UK reflects a rise in HIV incidence or an increase in HIV testing. METHODS: Estimates of HIV incidence were derived using data from UK HIV surveillance systems (HIV diagnoses; CD4 surveillance; unlinked anonymous surveys) for 1997-2004. Data on HIV testing were provided by KC60 statutory returns, voluntary testing and unlinked anonymous surveys in sentinel genitourinary medicine (GUM) clinics. RESULTS: HIV diagnoses among MSM in the UK rose by 54% between 1997 and 2004 (from 1382 to 2124), with variation by age and geographical location. The number of HIV diagnoses among MSM <35 years of age in London showed no increase, but in all other groups it increased. Throughout the UK, uptake of HIV testing increased significantly among MSM attending GUM clinics between 1997 and 2004, including "at-risk" MSM (p<0.001). Direct incidence estimates (serological testing algorithm for recent HIV seroconversion assay) provided no evidence of a statistically significant increase or decrease in HIV incidence. Indirect estimates suggested that there may have been a rise in HIV incidence, but these estimates were influenced by the increased uptake of HIV testing. CONCLUSIONS: The number of HIV diagnoses increased among MSM in the UK between 1997 and 2004, except among younger MSM in London, in whom there was no change. The increase in HIV diagnoses among MSM in the UK since 1997 seems to reflect an increase in HIV testing rather than a rise in HIV incidence.

Adult↗

Lower HIV-2 plasma viral loads may explain differences between the natural histories of HIV-1 and HIV-2 infections.

To explain the low transmissibility and pathogenicity of HIV-2 infection's plasma viral loads in both HIV-1- and HIV-2-infected persons were compared by using the polymerase chain reaction (PCR)-based Amp-RT assay to measure levels of reverse transcriptase (RT) activity. The study comprised a total of 155 HIV-infected-people including 58 who were infected with HIV-2 with CD4+ cell counts <500 x 106/L (n = 15), CD4+ cell counts >500 x 106/L (n = 26), or with tuberculosis (TB; n = 17), and 97 HIV-1-infected people with CD4+ cell counts <500 x 106/L (n = 32), CD4+ cell counts >500 x 106/L (n = 25), or TB (n = 40). Among persons with CD4+ cell counts <500 x 106/L, 11 (73.3%) of 15 HIV-2-infected persons had detectable plasma RT activity compared with 25 (78.1%) of 32 HIV-1-infected persons (p =.725). However, the median HIV-2 plasma RT activity in this group was significantly lower (2561 x 10-10 U/ml; p =.036; detectable range, 1712-644,868 x 10-10 U/ml) than the RT activity of HIV-1-infected persons with similar CD4+ cell counts (13,241 x 10-10 U/ml; detectable range, 8482-1,478,880 x 10-10 U/ml). Among TB patients, 10 (58.8%) of 17 HIV-2-infected persons had detectable plasma RT activity compared with 30 (75%) of 40 HIV-1-infected persons (p =.342). In contrast, among patients with CD4+ cell counts >500 x 106/L, none of 26 HIV-2-infected persons had detectable RT activity compared with 13 (52%) of 25 HIV-1-infected persons (p <.001). Our data suggest that unlike HIV-1 infection, HIV-2 infections with CD4+ cell counts >500 x 106/L are associated with a low level of viral replication, which may explain the longer clinical latency and lower transmissibility seen in HIV-2 infection.

CD4 Lymphocyte Count↗

Suppression of HIV replication in vitro by CD8+ T-cells from HIV-infected and HIV-seronegative individuals.

The inhibitory effect of CD8+ T-cells from HIV-infected or HIV-seronegative individuals on HIV replication in the naturally-infected CD4+ T-cells in vitro was examined. Not only autologous CD8+ T-cells from HIV-infected individuals but also allogeneic CD8+ T-cells from HIV-seronegative individuals prevented or delayed HIV replication, even in transwell cocultures using a semi-permeable 0.45 micron filter. The level of the inhibitory effect of allogeneic CD8+ T-cells from the HIV-seronegative individuals on the HIV replication was varied among CD4+ T-cells obtained from HIV-infected individuals used. The results suggested that CD8+ T-cells from HIV-seronegative individuals as well as HIV-infected individuals could produce some cytokine(s) which suppress HIV replication in vitro. The sensitivity to the cytokine(s) might be variable among HIV strains, depending on differences in the nucleotide sequence of different HIV-1 strains. Further studies of control of HIV replication by CD8+ anti-HIV cytokine(s) should provide new strategies for the therapy of HIV infection.

CD8-Positive T-Lymphocytes↗

Maintenance of HIV-specific CD4+ T cell help distinguishes HIV-2 from HIV-1 infection.

Unlike HIV-1-infected people, most HIV-2-infected subjects maintain a healthy CD4+ T cell count and a strong HIV-specific CD4+ T cell response. To define the cellular immunological correlates of good prognosis in HIV-2 infection, we conducted a cross-sectional study of HIV Gag-specific T cell function in HIV-1- and HIV-2-infected Gambians. Using cytokine flow cytometry and lymphoproliferation assays, we show that HIV-specific CD4+ T cells from HIV-2-infected individuals maintained proliferative capacity, were not terminally differentiated (CD57-), and more frequently produced IFN-gamma or IL-2 than CD4+ T cells from HIV-1-infected donors. Polyfunctional (IFN-gamma+/IL-2+) HIV-specific CD4+ T cells were found exclusively in HIV-2+ donors. The disparity in CD4+ T cell responses between asymptomatic HIV-1- and HIV-2-infected subjects was not associated with differences in the proliferative capacity of HIV-specific CD8+ T cells. This study demonstrates that HIV-2-infected donors have a well-preserved and functionally heterogeneous HIV-specific memory CD4+ T cell response that is associated with delayed disease progression in the majority of infected people.

CD4 Lymphocyte Count↗