Monitoring HPV type-specific prevalence over time through clinic-based surveillance: a perspective on vaccine effectiveness.

We investigated the feasibility of monitoring trends in prevalence of vaccine-preventable human papillomavirus (HPV) types in different clinic populations. We collected cervical specimens from women presenting to family planning, primary care, and sexually transmitted disease (STD) clinics for routine pap smears in five US cities during 2003-2005. We performed HPV genotyping and calculated annual type-specific prevalences; pre-vaccine era prevalence was highest for HPV 16 (6.0; 95% confidence interval [CI] 5.5-6.6%) and annual prevalences for vaccine-preventable types were stable, with few exceptions, after controlling for clinic type, age group, and city. With sufficient sample size and stable population characteristics, clinic-based surveillance systems can contribute to monitoring HPV vaccine impact in the cervical screening population.

Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons.

Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs raises public health concerns. Through surveillance of drug-resistant HIV-1 in 603 treatment-naive, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. These mutations included 215D/C/S and were found in 20 patients (3.3%). The 215D, 215C, and 215S mutations differ from 215Y by a 1-nt change compared with 2 nt for the WT T215 and likely represent revertants of 215Y. These viruses all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1(T215). However, differences in fitness among HIV-1(215D), HIV-1(215C), and HIV-1(215S) were seen when RT backgrounds were changed, demonstrating a role of the RT background in the selection of these revertants. In vitro selection with AZT showed that HIV-1(215D) and HIV-1(215C) acquired 215Y more rapidly than did WT HIV-1(T215), likely reflecting the need for only 1-nt change to evolve to 215Y. Our study demonstrates that HIV-1 with unusual mutations at codon 215 replicate efficiently, have WT susceptibility, and are commonly found in treatment-naive persons. The increased ability for selecting resistance mutations defines this class of WT HIV-1 and highlights the higher potential of these viruses to compromise the efficacy of antiretroviral therapy.

Substitution model of sequence evolution for the human immunodeficiency virus type 1 subtype B gp120 gene over the C2-V5 region.

Phylogenetic analyses frequently rely on models of sequence evolution that detail nucleotide substitution rates, nucleotide frequencies, and site-to-site rate heterogeneity. These models can influence hypothesis testing and can affect the accuracy of phylogenetic inferences. Maximum likelihood methods of simultaneously constructing phylogenetic tree topologies and estimating model parameters are computationally intensive, and are not feasible for sample sizes of 25 or greater using personal computers. Techniques that initially construct a tree topology and then use this non-maximized topology to estimate ML substitution rates, however, can quickly arrive at a model of sequence evolution. The accuracy of this two-step estimation technique was tested using simulated data sets with known model parameters. The results showed that for a star-like topology, as is often seen in human immunodeficiency virus type 1 (HIV-1) subtype B sequences, a random starting topology could produce nucleotide substitution rates that were not statistically different than the true rates. Samples were isolated from 100 HIV-1 subtype B infected individuals from the United States and a 620 nt region of the env gene was sequenced for each sample. The sequence data were used to obtain a substitution model of sequence evolution specific for HIV-1 subtype B env by estimating nucleotide substitution rates and the site-to-site heterogeneity in 100 individuals from the United States. The method of estimating the model should provide users of large data sets with a way to quickly compute a model of sequence evolution, while the nucleotide substitution model we identified should prove useful in the phylogenetic analysis of HIV-1 subtype B env sequences.

HIV incidence among repeat HIV testers at a county hospital, San Francisco, California, USA.

OBJECTIVES: To estimate HIV incidence, characterize correlates of HIV seroconversion, and monitor temporal trends in HIV transmission among patients repeatedly tested for HIV by a county hospital in San Francisco. DESIGN: Retrospective longitudinal study. METHODS: HIV incidence was retrospectively calculated among persons voluntarily tested for HIV antibody more than once at San Francisco's county hospital or one of its affiliated satellite community clinics between 1993 and 1999. Linkage of HIV test results in computerized databases identified "seroconverters" as individuals who had a negative antibody test followed by a positive test. The interval between tests was used as the person-time at risk. Cox proportional hazards analysis identified correlates of HIV seroconversion. RESULTS: A total of 84 HIV seroconversions were identified among 2893 eligible patients repeatedly tested for HIV antibody over a cumulative 5860 person-years (PYs) (incidence of 1.4 per 100 PYs, 95% confidence interval [CI]: 1.2-1.7). The majority of seroconversions (71 [84.5%]) were among injection drug users (IDUs) (incidence of 2.0 per 100 PYs, CI: 1.6-2.4). HIV incidence was highest among men who have sex with men (MSM) who were also IDUs (incidence of 3.8 per 100 PYs, CI: 2.7-5.1) and lowest among non-IDUs, heterosexual men, and non-IDU women (incidence of 0.3 per 100 PYs, CI: 0.1-0.6). In multivariate analysis, correlates of HIV seroconversion were age 25 to 29 years (hazard ratio [HR] = 3.9, CI: 2.4-6.3), MSM (HR = 2.9, CI: 1.9-4.4), and IDU (HR = 3.2, CI: 1.8-5.8). Overall, no temporal trend in annual HIV incidence was noted during the study period; however, HIV incidence among MSM IDUs increased from 2.9 per 100 PYs in 1996 to 4.7 per 100 PYs in 1998. CONCLUSIONS: The rate of seroconversion in this hospital and affiliated clinic population is unexpectedly high. Moreover, HIV transmission among IDU patients has not decreased over the last several years. The San Francisco county hospital provides a high-risk sentinel population to monitor emerging trends in HIV transmission, especially among IDUs, and presents multiple opportunities for prevention interventions, because these patients are being seen repeatedly by clinicians.

Analysis of dynamic cohort data.

Left-truncated and interval-censored data, termed dynamic cohort data, arise in longitudinal studies with rolling admissions and only occasional follow-up. The authors compared four approaches for analyzing such data: a constant hazard model; maximum likelihood estimation with flexible parametric models; the midpoint method, in which the midpoint of the last negative and first positive test result is used in a Cox proportional hazards model that accounts for left truncation; and a semiparametric method that uses imputed failure times in the Cox model. By using a simulation study, they assessed the performance of these approaches under conditions that can arise in observational studies: changes in disease incidence and changes in the underlying population. The simulation results indicated that the constant hazard model and midpoint method were inadequate and that the flexible parametric model was useful when enough parameters were used in modeling the baseline hazard. The semiparametric method ensured correct parameter (odds ratio) estimation when the baseline hazard was misspecified, but the trade-off increased computational complexity. In this paper, a study of the incidence of human immunodeficiency virus in patients repeatedly tested for the virus at a sexually transmitted disease clinic in New Orleans, Louisiana, illustrates the methods used.

Differences in the temporal trends of HIV seroincidence and seroprevalence among sexually transmitted disease clinic patients, 1989-1998: application of the serologic testing algorithm for recent HIV seroconversion.

The authors compared temporal trends in the prevalence and incidence of human immunodeficiency virus (HIV) infection based upon 34,866 specimens from patients who attended the San Francisco, California, municipal sexually transmitted disease clinic between 1989 and 1998. HIV infection data were collected during annual blinded HIV serologic surveys. Incidence was determined by applying a serologic testing algorithm for recent HIV seroconversion that uses both a sensitive and a less sensitive enzyme immunoassay to stored HIV positive sera. The HIV seroprevalence declined from 15.2% in 1989 to 7.2% in 1998 (odds ratio per year = 0.92, 95% confidence interval (CI): 0.91, 0.94). Among homosexual men, the HIV prevalence declined from 50.9% in 1989 to 19.9% in 1998 (odds ratio per year = 0.86, 95% CI: 0.85, 0.88). The pooled seroincidence was 1.6% and did not change significantly over time (odds ratio per year = 1.0, 95% CI: 0.98, 1.1). The pooled seroincidence among homosexual men was 6.6% per year and remained steady between 1989 and 1998 (odds ratio per year = 0.99, 95% CI: 0.92, 1.1). During a dramatic, 10-year decline in seroprevalence of HIV infection, the incidence of HIV infection remained remarkably stable.

Prevalence of mutations associated with reduced antiretroviral drug susceptibility among human immunodeficiency virus type 1 seroconverters in the United States, 1993-1998.

To assess the prevalence of mutations associated with decreased antiretroviral drug susceptibility, specimens were tested from persons infected with human immunodeficiency virus (HIV) during 1993-1998. Subjects were drug naive and were attending sexually transmitted disease clinics in 6 US cities. All were enrolled consecutively and had tested negative for HIV during the 2 years before enrollment. Plasma specimens from patients having >/=1 reverse transcriptase (RT) or primary protease mutation were tested phenotypically with a recombinant virus assay. Of 99 patients, 6 (6%) had mutations associated with zidovudine resistance, 2 (2%) had mutations associated with nonnucleoside RT inhibitor resistance, and 1 (1%) had a primary protease mutation. Overall, the prevalence of resistance-associated primary mutations was 5%, although high levels of decreased drug susceptibility (IC(50)s >/=10 times that of a reference virus) were observed in just 1%. These findings confirm the transmission of these mutations to drug-naive persons.

HIV seroincidence and risk factors among patients repeatedly tested for HIV attending sexually transmitted disease clinics in the United States, 1991 to 1996. STD Clinic HIV Seroincidence Study Group.

To assess the incidence of HIV infection and risk factors associated with HIV seroconversion among patients attending clinics for sexually transmitted diseases (STD), medical record reviews were conducted in 12 clinics in 7 U.S. cities. The records of all patients who initially tested negative for HIV from 1991 through 1996 and who received at least one additional HIV test during the study period were reviewed. In each of 7 cities, 5 to 112 patients seroconverted. Of the 286 seroconverters identified in total, 53% (152 of 286) were heterosexual men and 28% (81 of 286) were women. HIV incidence rates among men who have sex with men (MSM) ranged by city from 0.81 to 7.0 new infections/100 person-years. Rates among heterosexual men and women ranged from 0.018 to 1.2 infections/100 person-years. Multivariate analyses showed that drug use was associated with HIV seroconversion only among heterosexuals. Most new HIV infections in these clinics are being transmitted heterosexually and are associated with drug use. Nevertheless, MSM, particularly young MSM, are at greatest risk for HIV in this population: 1 of 47 seroconvert/year. The effective use of targeted prevention efforts depends upon the continued ability to monitor the incidence of HIV infection.

Neurosyphilis during the AIDS epidemic, San Francisco, 1985-1992.

To investigate the epidemiology and clinical spectrum of neurosyphilis in a population with high rates of coexisting syphilis and human immunodeficiency virus (HIV) infection, a retrospective analysis of cases in all San Francisco hospitals from 1985 to 1992 was conducted. Neurosyphilis was defined by a newly reactive cerebrospinal fluid VDRL; 117 patients with neurosyphilis were identified. The median age was 39 years, 91% were male, 74 (63%) were white, and 75 (64%) were HIV-infected. Thirty-eight (33%) presented with an early symptomatic neurosyphilis syndrome. Six (5%) had late neurosyphilis. Thirty-eight (32%) patients were asymptomatic, and 35 (30%) had findings attributable to coexisting neurologic diseases. Patients demonstrated high serum nontreponemal (VDRL) titers (median, 1:128) at neurosyphilis presentation. In contrast to the findings from the preantibiotic era, neurosyphilis was identified in young patients most often with HIV coinfection, and early symptomatic syndromes were identified more frequently than late neurosyphilis syndromes.

Trends in HIV seroprevalence among persons attending sexually transmitted disease clinics in the United States, 1988-1992.

Trends in seroprevalence of the human immunodeficiency virus (HIV) were examined among patients attending sentinel clinics for sexually transmitted diseases (STDs) throughout the United States. Cross-sectional, unlinked (blinded) surveys of HIV seroprevalence were conducted annually within clinics in 40 metropolitan areas. From 1988 to 1992, 552,665 specimens were tested in 80 STD clinics. The overall HIV seroprevalence was 33% (range among metropolitan areas: 5-52%) among gay and bisexual men, 3% (range: 0.3-11%) among heterosexual men, 2% (range: 0.1-11%) among women, and 10% (range: 0.5-45%) among heterosexual injecting drug users (IDUs). Controlling for clinic, age, and race/ethnicity, HIV seroprevalence decreased among all gay and bisexual men, but especially among white gay and bisexual men from 32% in 1989 to 22% in 1992. Among heterosexual men and women, HIV seroprevalence decreased among whites and, to a lesser degree, Hispanics, but remained essentially stable among African-Americans over time. Among heterosexual IDUs, seroprevalence was also unchanged. These results reflect changes in the HIV epidemic, which is becoming increasingly characterized by infected heterosexuals and IDUs, especially within minority populations.

Routine hepatitis B vaccination in a clinic for sexually transmitted diseases.

Patients were assigned to one of two vaccine schedules to assess the feasibility of vaccinating a sexually transmitted disease clinic population against hepatitis B virus. Of 1386 patients entering an inner-city clinic between June and July 1990, 611 (44%) accepted a first dose of vaccine. Twenty-one percent of all susceptible patients received at least two doses of vaccine. Annualizing these findings shows that an ongoing program could prevent 636 hepatitis B virus infections per year. Although a significant proportion of sexually transmitted disease clinic patients can be successfully vaccinated, strategies for preventing hepatitis B virus infections in this high-risk population must consider patient behavior as well as vaccine efficacy.

Chlamydia trachomatis infections.

Chlamydia trachomatis infections are the most common bacterial cause of sexually transmitted disease in the United States. Although precise incidence of infection is not known, it has been calculated that more than 4 million chlamydial infections occur each year. This article discusses the epidemiology of sexually transmitted chlamydial infections, the spectrum of clinical manifestations and their sequelae, the laboratory diagnosis of genital infections, and antibiotic treatment, emphasizing the significance of these issues for control efforts in the United States.

Factors associated with condom use in a high-risk heterosexual population.

The use of condoms has been advocated as a means of preventing the transmission of the human immunodeficiency virus and other sexually transmitted agents. To better understand factors that may influence condom use, 300 heterosexuals were enrolled in a cross-sectional study of patients attending San Francisco's only public sexually transmitted disease clinic. Interviewer-administered questionnaires were conducted. Condom use at last sexual intercourse was examined by logistic regression analysis. Men who used drugs or alcohol at last intercourse and whose partners did not want to use condoms were less likely to have used them; women who were black or Hispanic, who reported difficulty getting their partners to use condoms, or who reported that condoms decrease sexual pleasure also were less likely to have used them. Efforts to increase condom use in this population should target minorities, assist women to negotiate their use, emphasize the dangers of using alcohol and other drugs with sex, and address the perception that condoms interfere with sexual pleasure.

PIP: Better information is needed to understand sexual behavior and other variables that may influence condom use in order to develop successful education campaigns promoting their use. To this end, this study examined the AIDS Risk Reduction Model among an equal number of men and women (300) attending the public sexually transmitted disease (STD) clinic in San Francisco in 1989. The population is indicative of the population diagnosed with syphilis and gonorrhea. Clinical data from medical charts were linked with questionnaire data. Variables that were identified as affecting condom use at last intercourse were perceived susceptibility to HIV infection, knowledge of HIV transmission, and perception of the seriousness of HIV infection. Also included were condom use factors such as ill fit of condoms or decreased sexual spontaneity, and sexual communication. Attitudes and beliefs were scaled items which had to have alpha coefficients greater than .60 in order to be included. Evaluation of significant factors was accomplished with the Mantel-Haenzel chi-square and student's t-test. Gender specific multivariate logistic regression was used to control for confounding factors such as age, stability of the relationship, and total number of sex partners in a year. Condom breakage was reported. The population was 57% (78) male and black or Hispanic and 51% (84) female and black or Hispanic. 46% (138) had incomes of $5000. 47% were newly diagnosed with an STD on the interview day. 64% had prior STDs. 2 reported having HIV infection and 2 reported having a sex partner with HIV infection. 51% stated that their steady partner had at least one STD during the prior sexual encounters. Sexual behavior was reported for partner's sexual involvement with others in the past 2 months, condom use among steady and casual partners, knowledge of HIV transmission, past condom usage, and use of condoms at last intercourse. In the multivariate analysis, black or Hispanic men who used drugs or alcohol at last sexual encounter and black or Hispanic men whose partners did not want to use condoms were less likely to use condoms at last intercourse. Less condom use for women was associated with blacks or Hispanics, the belief that condoms reduce sexual pleasure, the difficulty in exercising control over their use, and involvement with a steady partner.

Hepatitis C virus infection among patients attending a clinic for sexually transmitted diseases.

OBJECTIVE: To evaluate the association between hepatitis C virus (HCV) infection and sexual behavior in a sexually active population. DESIGN: Cross-sectional study. SETTING: Inner-city clinic for sexually transmitted diseases. SUBJECTS: The study included 1292 patients attending the clinic for care during a 1-month period and having syphilis serologic tests performed. OUTCOME MEASURES: Antibody to HCV (anti-HCV) positivity as defined by a repeatedly-reactive enzyme immunoassay and a positive neutralization enzyme immunoassay (Abbott Laboratories, Chicago, Ill). RESULTS: Of 1292 patients screened for anti-HCV, 99 (7.7%) were positive. Logistic regression analysis found that patients who reported intravenous drug use, were positive for antibody to hepatitis B core antigen, reported a history of a blood transfusion, were black, or reported crack cocaine use were more likely to be anti-HCV-positive. Forty-five percent of patients who were anti-HCV-positive reported intravenous drug use. Sex with an intravenous drug user and a history of gonorrhea and syphilis were associated with anti-HCV positivity in a univariate analysis, but after controlling for confounding variables, no such associations remained. While having multiple sexual partners in the previous 3 months, being homosexual or bisexual, and engaging in receptive anal intercourse were associated with being positive for antibody to hepatitis B core antigen, those behaviors were not associated with anti-HCV positivity. CONCLUSIONS: While these results cannot exclude a role for the sexual transmission of HCV, they do suggest that, in this sexually active population, the sexual transmission of HCV occurs infrequently and that HCV is largely associated with intravenous drug use.

Chlamydia trachomatis infection in women: a need for universal screening in high prevalence populations?

Chlamydia trachomatis is the most prevalent sexually transmitted bacterial pathogen. Nevertheless, selective, rather than universal, screening for chlamydia has been recommended, largely because testing is expensive and requires considerable technical expertise. A total of 1,348 women in four family planning clinics in San Francisco, California, were screened from March 1987 to January 1988 to identify criteria for selective screening. Of these, 9.2% had a positive chlamydia test using direct fluorescence. Logistic regression analysis identified five factors associated with infection: age less than 25 years, cervical friability, single marital status, a new sexual partner within the past 3 months, and lack of barrier contraceptive use. No single risk factor or combination of risk factors had both a high sensitivity and a high positive predictive value for infection. While screening all women who were unmarried would detect 93% of those with chlamydia, the positive predictive value of 10.7% was not much higher than the overall prevalence. Conversely, screening all women with cervical friability, which had a positive predictive value of 23.2%, would only detect 11% of those with chlamydia. On the basis of the authors' findings, selective screening should not be used in high prevalence populations in which all women are at risk and should be screened for chlamydia.

Bancroftian filariasis in Puerto Limón, Costa Rica.

In four neighborhoods of Puerto Limón, a Caribbean coastal city in a tropical rainforest area of Costa Rica, examination of 1-ml samples of night blood from 1,142 randomly selected, and 1,196 associated, persons by the Knott and filter-chamber techniques revealed microfilariae of Wuchereria bancrofti in about 3% of the 2,338 samples. The frequency of infection was higher in males (3.9%) than in females (1.9%), higher in persons of black (4.1%) than of white (1.0%) race, and highest in persons aged 10-19 (4.0%) and over 50 years (4.8%), lowest in those under 10 years (1.1%). The median microfilaria density was 3.5, the highest 45, per 20 lambdas of blood. Microfilaremia was distinctly periodic. Dissection of 663 female Culex pipiens fatigans from 42 houses of infected persons revealed filarial larvae in 25; only 1 larva was third (infective) stage. Of 64 infected persons, 11 had clinical findings suggestive of filariasis. Elephantiasis was seen in 21 others. Other forms of symptomatic filariasis without microfilaremia, though presumed to be present, were not assessed specifically.