(C2) Saliva, breast milk, and mucosal fluids in HIV transmission.

The oral environment has received various amounts of attention in association with HIV infection and pathogenesis. Since HIV infection occurs through mucosal tissue, oral factors-including tissue, fluids, and compartments-are of interest in furthering our understanding of the diagnosis, infectivity, transmission, and pathogenesis of disease. This report reviews: (1) HIV testing and diagnoses with oral fluids; (2) post-natal acquisition of HIV in association with breast-feeding from HIV-positive mothers; and (3) oral sex and HIV transmission. In the first, we examine how oral fluids are used to detect HIV infection and review current consensus on the role of salivary molecules as markers for immunosuppression. Second, lactation-associated HIV acquisition is reviewed, with special consideration of emerging issues associated with the impact of anti-retroviral therapies. Last, we consider current data on the risk of HIV infection in association with oral sex. Investigation of these diverse topics has a common goal: understanding how HIV presents in the oral environment, with an aim to rapid and accessible HIV diagnosis, and improved prevention and treatment of infection.

Evaluating national HIV prevention indicators: a case study in San Francisco.

OBJECTIVES: To field-test the availability, interpretability, and programmatic usefulness of 37 proposed national HIV prevention indicators (HPI) intended to evaluate community-level impact of HIV prevention efforts in San Francisco. METHODS: HPI were defined for four populations (high risk heterosexuals, injecting drug users, men who have sex with men, and childbearing women) and for four domains (biological, behavioral, service, and socio-political). HPI were obtained from existing data sources only. Trends in HPI were examined from 1990 to 1997. RESULTS: Existing data provided 29 (78%) of the 37 proposed HPI; eight HPI were not available because California does not have HIV case reporting. Interpretation was limited for several HPI due to small sample size, inconsistencies in data collection, or lack of contextual information. Data providing behavioral HPI were scarce. HPI were consistent with historical patterns of HIV transmission in San Francisco but also highlighted new and worrisome trends. Notably, HPI identified recent increases in risk for HIV transmission among men who have sex with men. CONCLUSIONS: Despite limitations, the proposed national HPI provided evidence of the aggregate effectiveness of prevention efforts in San Francisco. Supplemental or local HPI are needed to fill data gaps, add context, and increase the scope and programmatic usefulness of the national HPI.

Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters.

OBJECTIVE: To identify appropriate criteria for characterizing HIV-infected nonprogressors. DESIGN: Five definitions were compared as follows: (1) last CD4 count > 500 x 10(6)/l; (2) two most recent CD4 counts > 500 x 10(6)/l; (3) calculated CD4 count based on linear regression > 500 x 10(6)/l; (4) CD4 slope > or = 0 with no antiretroviral use; (5) all CD4 counts > 500 x 10(6)/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. PARTICIPANTS: Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. MAIN OUTCOME MEASURES: Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. RESULTS: Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1-3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1-3. None of the definitions classified the same subjects as nonprogressors at any timepoint. CONCLUSIONS: Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.

CDC HIV prevention indicators: monitoring and evaluating HIV prevention in the USA.

OBJECTIVE: This study selected and field tested indicators to track changes in HIV prevention effectiveness in the USA. METHODS: During 1996-1999, the Centers for Disease Control and Prevention held two 2 day expert consultations with more than 80 national, state and local experts. A consensus-driven, evidence-based approach was used to select 70 indicators, which had to be derived from existing data, available in more than 25 states, and meaningful to state health officials in monitoring HIV. A literature review was performed for each indicator to determine general relevance, validity, and reliability. Two field tests in five US sites determined accessibility, feasibility, and usefulness. RESULTS: The final 37 core indicators represent four categories: biological, behavioral, services, and socio-political. Specific indicators reflect the epidemic and associated risk factors for men who have sex with men, injection drug users, heterosexuals at high risk, and childbearing women. CONCLUSIONS: Despite limitations, the indicators sparked the regular, proactive integration and review of monitoring data, facilitating a more effective use of data in HIV prevention community planning.

Comorbidity and survival in HIV-infected men in the San Francisco Men's Health Survey.

The course of disease associated with infection with the human immunodeficiency virus varies widely. Some patients deteriorate rapidly, while others live for years, even after an illness that defines the acquired immunodeficiency syndrome (AIDS). In this study, comorbidity, or the presence of concurrent health problems, was investigated prospectively as a possible co-factor for different rates of decline in 395 homosexual/bisexual men in the San Francisco Men's Health Study (SFMHS) who were infected with the human immunodeficiency virus (HIV). Comorbidity data obtained from baseline interviews included both chronic and infectious diseases as well as depression. Smoking, alcohol, and drug use were also examined. The most prevalent comorbid conditions were sexually transmitted diseases (90%) and hepatitis B infection (76%). Most chronic and acute concurrent health conditions were not significant discrete predictors of survival to AIDS or death after controlling for immune status and markers of disease progression. Significantly, other risk factors (e.g., depression and smoking) were found to be associated with more rapid progression. Men with symptoms of depression had a higher risk of progression of AIDS diagnosis; the relative hazard (RH) was 1.4 (95% confidence interval [CI], 1.00-2.08); smoking was associated with higher risk of death (RH, 1.6; 95% CI, 1.20-2.17). Older age was marginally associated with poorer survival to death. No associations were found between survival and alcohol and drug use.

Correlates of heavy substance use among young gay and bisexual men: The San Francisco Young Men's Health Study.

Correlates of heavy substance use among a household-based sample of young gay and bisexual men (n=428) were identified and the odds ratio (OR) was calculated. A total of 13.6% reported frequent, heavy alcohol use and 43% reported polydrug use. Compared with men employed in professional occupations, men in service positions (OR=3.77) and sales positions (OR=2.51) were more likely to be heavy alcohol consumers. Frequent gay bar attendance and multiple sex partners were related to heavy alcohol use, as well as to polydrug use. Polydrug users were more likely to be HIV seropositive (OR=2.05) or of unknown HIV serostatus (OR=2.78). HIV serostatus was similarly related to frequent drug use. These correlates of heavier substance use among young gay and bisexual men could be used to identify and intervene early with members of this population who are at risk of substance misuse, as well as HIV/AIDS risk.

Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection.

Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes.

Correlates of HIV risk in a random sample of street youths in San Francisco.

In a random sample of 203 street youths recruited in the Haight-Ashbury neighborhood of San Francisco, the authors found significant differences between those who reported that they could go home if they wanted to compared to those who perceived that they could not go back home. Those who could not go home were significantly more likely to report having been away from home for more than 3 years, having run away before age 13, having been kicked out of their home, and not being in touch with their parents compared to the other group. Those who could not go home reported significantly more-injection drug use, which puts them at high risk for HIV. Health care providers can identify street youths at highest risk by asking the question "Could you go back home today if you wanted to do so?"

Absence of HCV viral recombination following superinfection.

We sought evidence of viral recombination in five recently hepatitis C virus (HCV) infected young injection drug users who became superinfected with a distinguishable strain of HCV. The entire open reading frame of plasma HCV genomes was reverse transcribed, polymerase chain reaction amplified in two fragments, and directly sequenced. In two cases of same subtype (1a > 1a) superinfections the initial and later strains were both sequenced and compared for evidence of recombination. In three cases of superinfection with strains of different genotype/subtype (3a > 1a, 1a > 3a, 1b > 1a), the later time point HCV genomes were sequenced and compared with representative genomes of the initial genotype/subtype. No evidence of intra- or inter-genotype/subtype recombination was detected using six different programs for detecting recombination. We conclude that the generation of viable recombinant HCV genomes able to dominate in the viral quasispecies is a rare event.

Health indicators among low income women who report a history of sex work: the population based Northern California Young Women's Survey.

OBJECTIVES: We examined differences in demographic characteristics, HIV related risk behaviour, prevalence of sexually transmitted infections (STI), and HIV and other health concerns among women with and without a history of sex work. METHODS: A secondary analysis of a population based, cross sectional survey of young, low income women in northern California. RESULTS: Of the 2543 women interviewed, 8.9% reported a history of sex work. These women reported more lifetime male sexual partners, were more likely to use drugs before sex, and were more likely to have a history of having sex with partners at high risk for HIV (that is, men who have sex with men, inject drugs, or were known to be HIV positive). They were significantly more likely to have positive serology for syphilis, herpes simplex virus type 2 (HSV-2), and hepatitis C regardless of their personal injecting drug use history; however, they were no more likely to have HIV, chlamydia, gonorrhoea, hepatitis A or hepatitis B infection compared to women without a history of sex work. Women with a history of sex work were significantly more likely to have a history of sexual coercion and tobacco use. CONCLUSIONS: These data measure the population prevalence of sex work among low income women and associated STI. Women with a history of sex work have health concerns beyond STI and HIV treatment and prevention.

Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco.

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross-sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti-HCV) among street-recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti-HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti-HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05-1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10-1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00-1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74-9.52), injected daily (OR, 3.85; 95% CI, 2.07-7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18-5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24-1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26-0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25-0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti-HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.

Sexual risk behavior and risk factors for HIV-1 seroconversion in homosexual men participating in the Tricontinental Seroconverter Study, 1982-1994.

Trends in sexual behavior associated with incident infection with human immunodeficiency virus (HIV) type 1 are described and a case-control study was conducted to examine risk factors for HIV seroconversion in homosexual men who became infected with HIV between 1982 and 1994 from four geographic sites: Amsterdam, the Netherlands; San Francisco, California; Vancouver, Canada; and Sydney, Australia. Changes in sexual behaviors were evaluated from cohort visits in the preseroconversion, seroconversion, and postseroconversion intervals and were further examined over three time periods: 1982-1984, 1985-1987, and 1988-1994. In a case-control study, sexual behaviors, substance use, and presence of sexually transmitted disease were compared between 345 HIV-positive cases and 345 seronegative controls matched by visit date and site. Receptive anal intercourse was the sexual behavior most highly associated with seroconversion. The odds ratio (OR) per receptive anal intercourse partner increase was 1.05 (95% confidence interval (CI) 1.02-1.09). To more carefully examine risk associated with receptive oral intercourse, analyses were done in a subgroup of men who reported no or one receptive anal intercourse partner. The risk (OR) associated with receptive oral intercourse partner increase was 1.05 (95% CI 1.0-1.11). In multivariate conditional logistic regression analyses, presence of sexually transmitted disease (OR = 3.39, 95% CI 1.95-5.91) and amphetamine use (OR = 2.55, 95% CI 1.26-5.15) were independently associated with seroconversion. Although the prevalence of major risk factors has decreased over time, the associations of these behaviors and HIV infection persist, suggesting that these risk behaviors remain important avenues for public health interventions.

Sexual transmission and the natural history of human herpesvirus 8 infection.

BACKGROUND: Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history. METHODS: The San Francisco Men's Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposi's sarcoma. RESULTS: Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposi's sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners. CONCLUSIONS: The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposi's sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually transmitted among men.

Transmission of HIV in the dental clinic and elsewhere.

This review focuses on the risk of transmission of HIV in dental practice in developed and developing countries; and as a result of oral sex, perinatal transmission and breast feeding. Postexposure prophylaxis (PEP) and practical measures to control cross-infection with TB are also discussed. There are few data from resource-poor countries where prevalence of HIV and risk of infection are higher--issues that deserve priority. Available information indicates that the risk of HIV transmission in the dental office is very low. Transmission of HIV from three healthcare workers to patients has been confirmed, including a dentist who infected six patients. There are >300 reports (102 confirmed) of occupational transmission to healthcare workers, including nine dental workers (unconfirmed). Exposure to HIV has been reported by 0.5% dentists/year. The risk of HIV infection after percutaneous exposure (0.3%) can be reduced by 81% with zidovudine PEP. However, risk assessment is required to assess the need and appropriate regimen. The risk of HIV transmission associated with orogenital sex exists, but is considered extremely low: barrier protection is recommended. Conversely, the proportion of babies who acquire HIV from untreated HIV-seropositive mothers is 15-25% in developed countries and 25-45% in developing countries. The frequency of HIV transmission attributable to breastfeeding is 16%. Airborne transmission of TB can be avoided by the prompt referral of known/suspected cases of active TB for chemotherapy, deferral of elective procedures until patients are not infectious, and the use of appropriate standard/isolation precautions including adequate ventilation of treatment areas.

Saliva and inhibition of HIV-1 infection: molecular mechanisms.

Oral fluids are rarely a vehicle for HIV-1 infection in vivo, unlike other mucosal secretions. This unique property raises questions regarding (1) the molecular mechanisms responsible for the lack of salivary transmission, (2) the extent to which oral immunological responses mirror responses at other mucosal sites, (3) the use of promising salivary markers of HIV-1 disease progression, (4) the relationship between oral and blood viral loads, (5) cofactors that influence oro-genital transmission, and (6) the feasibility of oral-based antibody testing for HIV-1 diagnosis in the home. This paper discusses these questions and provides background summaries, findings from new studies, consensus opinions, practical relevance to developing countries, and suggestions for future research agenda on each of the key topics.

Prevalence of HIV infection, sexually transmitted diseases, and hepatitis and related risk behavior in young women living in low-income neighborhoods of northern California.

OBJECTIVE: To estimate the prevalence of human immunodeficiency virus (HIV) infection, sexually transmitted diseases, and hepatitis and the associated sexual and drug-using behavior among women residing in low-income neighborhoods in 5 northern California counties. METHODS: From April 4, 1996, to January 6, 1998, women aged 18 to 29 years were recruited door-to-door from randomly selected street blocks within 1990 census block groups below the 10th percentile for median household income for each county. RESULTS: Of 24,223 dwellings enumerated, contact was made with residents from 19,546 (80.7%). Within contacted dwellings, 3,560 eligible women were identified and 2,545 enrolled (71.5%). Weighted estimates for disease prevalence were HIV infection, 0.3% (95% confidence interval, 0.1%-0.4%); syphilis, 0.7% (0.3%-1.1%); gonorrhea, 0.8% (0.3%-1.3%); chlamydia, 3.3% (2.4%-4.8%); herpes simplex virus, type 1, 73.7% (71.6%-76.9%); herpes simplex virus, type 2, 34.4% (29.9%-39.0%); hepatitis A, 33.5% (28.3%-38.7%); chronic hepatitis B, 0.8% (0.3%-1.2%); and hepatitis C, 2.5% (1.4%-3. 6%). Condom use at last sexual intercourse with a new partner was reported by 44.0% (33.9%-54.1%). Injection drug use in the last 6 months was reported by 1.8% (1.0%-2.7%). CONCLUSIONS: The Young Women's Survey provided population-based estimates of the prevalence of 8 infectious diseases and related risk behavior within a population for whom data are often difficult to collect. Population-based data are needed for appropriate targeting and planning of primary and secondary disease prevention.

Use of epidemiologically well-defined subjects and existing immunofluorescence assays to calibrate a new enzyme immunoassay for human herpesvirus 8 antibodies.

Agreement between assays for the detection of human herpesvirus 8 (HHV-8) antibodies has been limited. In part, this disagreement has been because assay calibration (i.e., differentiating positive from negative results) has not been done in a standardized fashion with reference to a wide spectrum of HHV-8-infected (true-positive) and HHV-8-uninfected (true-negative) persons. To describe the performance of an assay for HHV-8 antibodies more accurately, we used epidemiologically well-characterized subjects in conjunction with testing on two existing immunofluorescence assays for HHV-8 antibodies to define two groups: a group of 135 HHV-8-infected individuals (true positives), including Kaposi's sarcoma patients and those asymptomatically infected, and a group of 234 individuals with a high likelihood of being HHV-8 uninfected (true negatives). A new enzyme immunoassay (EIA), using lysed HHV-8 virion as the antigen target, was then developed. With the above true positives and true negatives as references, the sensitivity and specificity of the EIA associated with different cutoff values were determined. At the cutoff that maximized both sensitivity and specificity, sensitivity was 94% and specificity was 93%. When the EIA was used to test a separate validation group, a distribution of seropositivity that matched that predicted for the agent of Kaposi's sarcoma was observed: 55% of homosexual men were seropositive, versus 6% seropositivity in a group of children, women, and heterosexual men. It is proposed that the EIA has utility for large-scale use in a number of settings and that the calibration method described can be used for other assays, both to more accurately describe the performance of these assays and to permit more-valid interassay comparison.

Prevalence and correlates of herpes simplex virus type 2 infection in a population-based survey of young women in low-income neighborhoods of Northern California. The Young Women's Survey Team.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections and may enhance transmission of HIV. However, population-based estimates of HSV-2 prevalence and correlates of infection are rare. GOALS: To obtain population-based estimates of HSV-2 prevalence and to identify demographic and sexual behavioral correlates of infection among women in low-income communities of Northern California. STUDY DESIGN: A randomized, single-stage, cluster sample, cross-sectional survey of women age 18 to 29 years who reside in 1990 US Census block groups at the lowest tenth percentile for household income. RESULTS: The survey-weighted prevalence of HSV-2 infection was 34.8% (95% CI, 30.4-39.2). Factors independently associated with HSV-2 seropositivity were black race, older age, lower income, parity, greater number of lifetime male sexual partners, earlier onset of sexual intercourse, sex work, history of sexually transmitted disease (STD), and cocaine use. CONCLUSION: The high prevalence of HSV-2 and the strong correlation with sexual risk underscores the potential for further spread of STD, including HIV, in this young population.

Incidence and prognostic significance of symptomatic primary human immunodeficiency virus type 1 infection in homosexual men.

To investigate the incidence of symptomatic primary human immunodeficiency virus type 1 (HIV-1) infection and its prognostic significance for HIV-1 disease progression, data for 328 homosexual men from four cohort studies were evaluated. Rates of diarrhea, fever, night sweats, cough, and fatigue prior to, during, and after seroconversion were compared by use of Poisson regression, and the prognostic significance of these symptoms was evaluated with survival methods. The incidence of all symptoms was elevated during seroconversion; however, only fever was associated with faster disease progression. Seven or more days of fever was reported by 13.8% of subjects; half of them developed AIDS within 6 years, whereas only one-fourth of the men without fever developed AIDS within 6 years. In addition, fever was the only symptom associated with shortened survival and increased CD4 cell loss. Persons experiencing prolonged periods of fever during seroconversion should therefore be considered for early treatment, including prophylaxis against opportunistic infections and combinations of antiretroviral drugs.