Issues around childhood disclosure of HIV status - findings from a qualitative study in West Bengal, India.

INTRODUCTION: Informing the children living with HIV (CLH) about their disease (disclosure) is important from the perspective of disease treatment and overall psychosocial development. There are no published studies that qualitatively explored HIV disclosure-related issues among CLH in India. Our aim was to provide insights into the perceptions of informal caregivers of CLH regarding childhood disclosure. METHODS: Children were defined as those aged <16 years. In-depth interviews were conducted with 34 primary caregivers of CLH aged 8 to 15 years old who were residing in West Bengal, India. The participants were recruited with the help of a community-based organization that provides need-based services to people living with HIV. RESULTS: We obtained caregivers' perspectives on the motivators and barriers of childhood disclosure. Health benefits such as medication adherence emerged as an important motivator, while distress caused by disclosure and potential for stigma were identified as barriers. Health care providers were the preferred disclosers for most caregivers, followed by the caregivers themselves. Some caregivers wanted their child to learn about his/her HIV status by him/herself. There was no consensus among the caregivers about the ideal age for disclosure. Many preferred to wait until the child attained maturity or was of marriageable age. DISCUSSION: Disclosure of HIV status to children is an emotional issue, both for the caregiver and the child. Like most low-or middle-income countries, no standardized, age-appropriate disclosure guidelines exist in India. Our findings advocate adoption of a multi-faceted approach, including increased availability of social and familial support, for childhood HIV disclosure.

Differences in hepatitis C virus prevalence and clearance by mode of acquisition among men who have sex with men.

We examined the characteristics associated with hepatitis C virus (HCV) antibody (anti-HCV) prevalence and HCV clearance between injection drug using (IDU) and non-IDU men who have sex with men (MSM). Stored serum and plasma samples were tested for anti-HCV and HCV RNA to determine the HCV status of 6925 MSM at enrolment into the Multicentre AIDS Cohort Study (MACS). Prevalence and clearance ratios were calculated to determine the characteristics associated with HCV prevalence and clearance. Multivariable analyses were performed using Poisson regression methods with robust variance estimation. Anti-HCV prevalence was significantly higher among IDU than among non-IDU MSM (42.9% vs 4.0%), while clearance was significantly lower among IDU MSM (11.5% vs 34.5% among non-IDU MSM). HIV infection, Black race, and older age were independently associated with higher prevalence in both groups, while smoking, transfusion history, and syphilis were significantly associated with prevalence only among non-IDU MSM. The rs12979860-C/C genotype was the only characteristic independently associated with HCV clearance in both groups, but the effects of both rs12979860-C/C genotype [clearance ratio (CR) = 4.16 IDUs vs 1.71 non-IDUs; P = 0.03] and HBsAg positivity (CR = 5.06 IDUs vs 1.62 non-IDUs; P = 0.03) were significantly larger among IDU MSM. HIV infection was independently associated with lower HCV clearance only among non-IDU MSM (CR = 0.59, 95% CI = 0.40-0.87). IDU MSM have higher anti-HCV prevalence and lower HCV clearance than non-IDU MSM. Differences in the factors associated with HCV clearance suggest that the mechanisms driving the response to HCV may differ according to the mode of acquisition.

Rapid operation assessment of voluntary HIV counselling and testing services in three cities in China, 2009.

OBJECTIVES: To assess the operation of voluntary counselling and testing (VCT) services forhuman immunodeficiency virus (HIV) in three cities in China. STUDY DESIGN: A cross-sectional study using mixed methods, including focus group discussions,in-depth interviews, field assessment, archive checking and structured questionnaire interviews, was conducted to assess different aspects of VCT services. METHODS: Surveys were undertaken in six counties of three China Global Fund AIDS Program (Round Five) cities, including 11 VCT clinics, 38 counsellors, 83 clients and 332 individuals at risk for HIV infection. RESULTS: All counsellors were trained and approved for providing counselling. As there were adequate numbers of clinics and counsellors, VCT services ran smoothly. Clients were generally satisfied with VCT services and considered service operation to be adequate. Problems with the VCT programme included fewer VCT services in general hospitals, lack of a referral mechanism, and long delays between testing and receipt of results. CONCLUSIONS: The operation of VCT services in the three cities was generally adequate, but referral services were poor. More attention needs to be paid to HIV testing and counselling in general hospitals, and referral networks need to be strengthened.

The multicenter AIDS Cohort Study, 1983 to .

The Multicenter AIDS Cohort (MACS), initiated in 1983 at the Johns Hopkins School of Public Health, the University of Pittsburgh School of Public Health, Northwestern University School of Medicine, and the UCLA School of Public Health, continues to conduct studies and publish key papers on the natural history of untreated and treated HIV infection in 6972 men-who-have-sex-with-men. Through May 2011, 1,490,995 specimens have been collected, 86,883 person-years of data accrued and 1195 scientific papers published in international journals.

Impact of paediatric human immunodeficiency virus infection on children's and caregivers' daily functioning and well-being: a qualitative study.

BACKGROUND: Human immunodeficiency virus (HIV) infection impacts not only upon the physical health of affected children, but also their psychosocial functions, family relationships and economical status. Caregivers are confronted with complex challenges related to the physical, emotional and financial demands of raising these children. The purpose of this study was to enhance our understanding of the impact of HIV disease on both children's and caregivers' well-being, using a qualitative inquiry approach. METHODS: A total of 35 primary caregivers of HIV-infected children participated in in-depth interviews. The issues discussed included the major negative impacts on children's daily functioning and well-being, and the perceived caregiver/parental burden. Participants included parents (40%), grandparents (22.8%), other relatives (e.g. uncles, aunts) (34.3%) and one foster parent (2.8%). RESULTS: Qualitative analysis revealed that the major negative impacts of HIV/AIDS included physical symptoms, school performance and relationship changes. The major negative impacts on caregivers' well-being included acceptance of the diagnosis, dealing with the financial burden and keeping the diagnosis private. CONCLUSIONS: Approaches are needed to address these challenges by enhancing families' coping skills and building supportive networks.

KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma.

A major controversy regarding Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) is whether or not it is a ubiquitous infection of humans. Immunoassays based on KSHV- and Epstein-Barr virus (EBV)-coinfected cell lines show that most US AIDS-KS patients have specific antibodies to KSHV-related antigens. We have developed a sensitive indirect immunofluorescence assay (IFA) based on an EBV-negative, KSHV-infected cell line, BCP-1. When we used this IFA assay, KSHV-related antibodies were found in 71-88% of serum samples from US, Italian and Ugandan AIDS-KS patients, as well as all serum samples examined from HIV-seronegative KS patients. Although none of the US blood donors examined were KSHV seropositive by IFA, intermediate and high seroprevalence rates were found in Italian and Ugandan control populations. Antibody kinetics showed that more than half of the AIDS-KS patients who were examined IgG-seroconverted before KS development, and antibody levels did not decline after seroconversion. For these patients, seropositivity rates increased linearly with time, suggesting that the rate of infection was constant and that the risk of developing KS once infected with KSHV is not highly dependent on the duration of infection. These data strongly suggest that KSHV is not ubiquitous in most populations and that the virus may be under strict immunologic control in healthy KSHV-infected persons.

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Family support, quality of life and concurrent substance use among methadone maintenance therapy clients in China.

OBJECTIVES: The methadone maintenance therapy (MMT) programme has been scaled up rapidly in China. This study explored the family support perceived by MMT clients and its association with their quality of life and concurrent illicit drug use. STUDY DESIGN: Cross-sectional study. METHODS: Five hundred and sixty MMT clients were selected at random from 28 MMT clinics and services in Zhejiang and Jiangxi Provinces, China for participation in a face-to-face interview study. The participants' perceived family support and quality of life were measured through face-to-face structured interviews conducted by trained interviewers. Self-reported information about illicit drug use was obtained from clients. Urine specimens were collected from the participants to test for heroin use. RESULTS: Among the 560 participants, 471 (84.1%) were male and 168 (30.0%) were unemployed at the time of the study. In total, 398 (71.1%) were injecting drug users and 309 (55.2%) had a history of drug use of more than 10 years. Around one-third (n = 211, 37.7%) of the participants reported concurrent illicit drug use or had a positive urine test. Perceived family support was associated with increased physical health, psychological health, environmental health and social health. In addition, perceived family support was negatively correlated with concurrent substance use. CONCLUSIONS: Drug use and MMT is a family issue in China. Based on the findings of this study, it is suggested that involving family members in recruitment and interventions of the MMT programme will achieve higher rates of participation and compliance.

Higher risk of AIDS or death in patients with lower CD4 cell counts after virally suppressive HAART.

BACKGROUND: The clinical implications of a failure to achieve high CD4 cell counts while receiving virally suppressive highly active antiretroviral therapy (HAART) are uncertain. METHODS: We analysed data from HIV-infected men participating in the Multicenter AIDS Cohort Study (MACS) to elucidate associations between CD4 cell counts achieved during virally suppressive HAART and risks of AIDS or death. Inclusion criteria were: CD4 cell count <200 cells/microL before HAART initiation; >or=2 viral load (VL) determinations after HAART initiation; and sustained viral suppression, defined as all VL <50 HIV-1 RNA copies/mL, but allowing a single VL of 50-1000 copies/mL. RESULTS: One hundred and twenty-one men were included; median age was 42 years. After first VL <50 copies/mL, six participants had a new AIDS diagnosis and seven died. The median CD4 cell count change/year (cells/microL) after first VL <50 copies/mL was zero among patients who either developed AIDS or died vs. 39 among those who did not meet either endpoint (P=0.119). After controlling for time from HAART initiation to first VL <50 copies/mL, age at first VL <50 copies/mL, history of AIDS and antiretroviral therapy (ART) experience before HAART, the hazard ratio for AIDS or death at CD4 cell count of 350 cells/microL was 10.7 (P=0.013), and at CD4 cell count of 201-350 vs. >350 cells/microL was 8.54 (P=0.014). CONCLUSION: In this cohort, lower CD4 cell count at the time of viral suppression was associated with increased risk of AIDS or death.

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC)

Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.

Herpes simplex virus-2 infection in male rural migrants in Shanghai, China.

The overall herpes simplex virus (HSV)-2 seroprevalence was 5.5% among male rural migrants working in construction sites, markets and factories, 5.4% among those reporting having had sexual intercourse and 5.8% among those reporting no sexual intercourse. Multiple logistic regression analyses indicate that migrants having higher income were more likely to have HSV-2 infection. None of the HSV-2-positives realized their infection status. Future sexually transmitted disease (STD) intervention programmes should target migrants with higher income and migrant market vendors and should not exclude those who self-report no STDs or no history of sexual intercourse.

Human immunodeficiency virus-1 (HIV-1) gp120 superantigen-binding serum antibodies. A host factor in homosexual HIV-1 transmission.

HIV-1 gp120 is an immunoglobulin superantigen which can bind to preimmune serum Ig. We hypothesize that levels of such preimmune antibodies vary in the population and might affect host resistance or susceptibility to viral transmission. This study tests two predictions: (a) levels of preimmune anti-gpl20 Igs are a polymorphic trait; and, (b) these levels are correlated with resistance or susceptibility to HIV-1 transmission. The first prediction was confirmed in a longitudinal study of a low-risk seronegative population. In this group, levels of both endogenous anti-gpl20 IgM and IgG varied widely, but were characteristic and stable for each individual. The second prediction was addressed in a study of participants of the Multicenter AIDS Cohort Study, in which men "susceptible" and "resistant" to HIV infection were identified based on numbers of sexual partners and eventual seroconversion. Specimens consisted of archival sera obtained > 2 yr before seroconversion. Men in the susceptible population (low-risk seroconverters) were distinguished by low levels of anti-gpl20 IgG. We conclude that the level of preimmune anti-gpl20 IgG is a polymorphic population trait, and low levels are a potentially specific and significant factor in homosexual transmission of HIV infection.

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

Timing of antiretroviral therapy initiation after diagnosis of recent human immunodeficiency virus infection and CD4(+) T-cell recovery.

We retrospectively examined the timing of antiretroviral therapy (ART) initiation and CD4(+) T-cell recovery over 36 months among recent human immunodeficiency virus (HIV) infections using BED (HIV-1 subtypes B, E and D) immunoglobulin G capture enzyme immunoassay (BED-CEIA). Regardless of baseline CD4(+) counts, individuals (n = 393) who initiated ART >2 months after diagnosis had significantly decreased probability and rate of achieving CD4(+) counts ≥900 cells/µL or ≥600 cells/µL than those individuals (n = 135) who started ART earlier (≤2 months). But the mean CD4(+) counts in two groups converged after 30 months of treatment. Early ART initiation leads to accelerated CD4(+) recovery, but does not offer a long-term advantage in CD4(+) counts.

Applications of a computer simulation model of the natural history of CD4 T-cell number in HIV-infected individuals.

Data from the Multicenter AIDS Cohort Study (MACS) of 1637 gay men, recruited in 1984 and 1985 in Los Angeles and followed at 6-monthly intervals, are used to develop a computer simulation model of the typical pattern of CD4 T-cell number changes in HIV-infected AIDS-free subjects. The empirical model incorporates the following features: (1) within-person and between-person variability in CD4 measurements; (2) variation in the rates of decline of CD4 values; (3) variation in the level of CD4 at which clinical AIDS is diagnosed, and (4) greater absolute variation in CD4 values in men with high CD4 levels compared with men with low CD4 values. Three applications of the model to assist in the design and interpretation of clinical trials are given. Further applications to clinical trials and to estimate the current and future spectrum of HIV-mediated immunological disease in the USA, as measured by the CD4 values, are discussed.

Serum soluble CD8 molecule is a marker of CD8 T-cell activation in HIV-1 disease.

To characterize CD8 T-cell activation during HIV-1 infection we measured serum soluble CD8 (sCD8) levels longitudinally in seroconverters and in individuals with established HIV infection who were in different stages of illness. CD8 T-cell activation occurs very early in HIV infection. Serum sCD8 levels were elevated in 91.5% of the first seropositive samples in seroconverters. Furthermore, CD8 T-cell activation persists throughout HIV infection. sCD8 predicted the occurrence of AIDS in HIV-seropositive individuals and so the addition of serum sCD8 levels to CD4 T-cell measurements increased the power in predicting the onset of AIDS. The serum level of sCD8 was particularly relevant to the prediction of subsequent CD4 T-cell fall relatively early in infection, for example, in the 3 years after seroconversion. However, later in HIV infection, for example within 2 years prior to development of AIDS, sCD8 levels were less predictive. sCD8 correlated with levels of beta 2-microglobulin and neopterin, which reflect activation of cell types other than CD8. Thus, serum sCD8 level can be a useful marker of specific CD8 T-cell activation, and is an independent predictor of prognosis in HIV infection.

Prevalence of unprotected sex among men with AIDS in Los Angeles County, California 1995-1997.

OBJECTIVE: To determine the prevalence of unprotected sex among men with AIDS in Los Angeles County. DESIGN: Cross-sectional study. METHODS: All men aged > or = 18 years who were newly reported to the local health department with AIDS and completed a standardized interview between January 1995 and June 1997 were included in the study. Men were classified as having unprotected sex if they reported one or more sex partners during the past year with whom they had vaginal or anal sex and did not always use a condom. RESULTS: Of 617 men interviewed, 29% reported unprotected sex in the past year. The prevalence of unprotected sex was highest among men < 30 years of age (43%) and those who had first learned of their HIV-positive status < 12 months prior to interview (44%). In all, 323 (52%) men reported one or more male sex partners in the past year. Of these, 22% reported unprotected insertive anal sex and 27% unprotected receptive anal sex. One or more female partners in the past year was reported by 131 (21%) men. Of these, 53% reported unprotected vaginal sex and 18% unprotected anal sex. CONCLUSIONS: The findings highlight the importance of early HIV detection efforts, coupled with targeted and sustained HIV prevention services for those who test positive, to prevent ongoing transmission of the virus.

Immunologic effects of combined protease inhibitor and reverse transcriptase inhibitor therapy in previously treated chronic HIV-1 infection.

OBJECTIVE: To evaluate the efficacy of combination protease and reverse transcriptase inhibitor therapy in correcting HIV-1-induced lymphocyte subset abnormalities in previously treated adults. DESIGN: A 48-week observational study of lymphocyte subsets in 12 participants in the Multicenter AIDS Cohort Study who were already taking at least one reverse transcriptase inhibitor and added a protease inhibitor to their treatment regimen. Comparison groups were HIV-seronegative homosexual men, HIV-seronegative heterosexual men, and homosexual HIV-1-infected men who were long-term non-progressors. METHODS: Three-color immunofluorescence and monoclonal antibodies were used to assess HIV-1-induced lymphocyte subset alterations related to immune deficiency and immune activation. Plasma HIV-1 RNA levels were monitored to assess suppression of viral replication. RESULTS: CD4+ cell counts significantly increased and lymphocyte activation measured as CD38 and HLA-DR expression on CD8+ T cells significantly decreased by 48 weeks. CD4+ cell values remained abnormal even in those who were fully suppressed. Some T-cell activation markers decreased to levels observed in long-term non-progressors. The increase in CD4+ T-cell numbers reached a plateau by week 24, but the increase in resting HLA-DR- CD38-T cells was sustained through week 48. Proportions of CD45RA+ CD62L-selectin+ and CD28+ CD4+ T-cell subsets and Fas expression were not abnormal at baseline compared with seronegative homosexual controls. CONCLUSIONS: The most significant impact of suppression of viral replication was reversal of T-cell activation. However, normalization of lymphocyte subset perturbations associated with chronic HIV-1 infection was not achieved after 1 year of treatment with current combination antiretroviral regimens. More profound viral suppression, therapy for longer than 1 year, or immunologic augmentation may be needed to fully reverse the abnormalities.

Effectiveness of potent antiretroviral therapies on the incidence of opportunistic infections before and after AIDS diagnosis.

OBJECTIVES: To determine the effectiveness of potent antiretroviral therapy in reducing opportunistic infections (OI) as both a presenting event and subsequent to an AIDS-defining event. DESIGN AND METHODS: A total of 543 seroconverters and 1470 men with AIDS were compared for the time to development of OI as the presenting AIDS event and as a subsequent event in the 1984-1989, 1990-1992, 1993-1995, and 1996-1998 periods, when the major treatments were no therapy, monotherapy, combination therapy, and potent antiretroviral therapy, respectively. RESULTS: The seroconverters suffered 132 OI and the participants with AIDS had 717 OI. The relative hazard (RH) of OI as the presenting AIDS event declined by 81% in the calendar period when potent antiretroviral therapy was available compared with the monotherapy period. Declines were observed for Mycobacterium avium complex, cytomegalovirus disease, and esophageal candidiasis, but were statistically significant only for Pneumocystis carinii pneumonia. The RH of OI as a secondary infection dropped by 77% in the last calendar period compared with the monotherapy period. A significant decline was observed for all four OI. Prophylactic drug use did not increase in the era of potent antiretroviral therapy. CONCLUSION: The hazard of OI in the era of potent antiretroviral therapy has declined dramatically compared with the era of monotherapy, despite the concurrent decrease in the use of prophylactic drugs. Physicians should consider whether it is necessary to include prophylactic drugs as part of the complex drug regimen for patients on potent antiretroviral therapy.