Assessment of off-label use of denosumab 60 mg injection during the early postmarketing period using health insurance claims data.

UNLABELLED: Off-label use of denosumab 60 milligram (mg) injection was assessed within an administrative claims database. The completeness of claims to assess off-label use was investigated with medical record review. Potential denosumab 60 mg off-label use was observed based on claims, but many had evidence of on-label indications based on medical record review. INTRODUCTION: Denosumab 60 mg injection is approved in the USA to treat patients at high fracture risk due to postmenopausal osteoporosis, male osteoporosis, and hormone therapy for the treatment of prostate and breast cancers. Its RANK ligand-inhibiting effect makes it a candidate for the off-label treatment of other conditions mediated by the rate of bone resorption by osteoclasts. To better understand its utilization patterns, we assessed off-label use of denosumab 60 mg within an administrative claims database. METHODS: Definite, probable, and possible denosumab 60 mg users were identified during the early postmarketing period within a claims database of a US healthcare insurer. Medical record review confirmed a sample of these users. Off-label use among definite and probable users and all chart-confirmed users was classified using claims-derived age, dose interval, and diagnosis and treatment received relative to the administration date. Among chart-confirmed users classified as off-label, patient characteristics related to treatment indication were abstracted from medical records to investigate the completeness of claims to study off-label medication use. RESULTS: Off-label use was identified based on claims in approximately 25 % of definite and probable denosumab 60 mg users and 35 % of chart-confirmed users. Medical record review identified evidence of on-label indications in 81 % of chart-confirmed users classified as off-label in claims. CONCLUSIONS: Many of the off-label denosumab 60 mg users had diagnoses or treatment consistent with on-label indications based on medical record review, suggesting these are under-recorded in claims data. It is warranted to be cautious when using administrative databases to assess off-label medication use.

HIV prevalence, previous HIV testing, and condom use with clients and regular partners among Senegalese commercial sex workers.

OBJECTIVES: To assess HIV prevalence and risk factors for HIV infection, to investigate condom use among registered female commercial sex workers (CSWs) in Senegal, West Africa, and to examine the association between previous HIV testing, knowledge of HIV serostatus and condom use with both regular sex partners and clients within this population. METHODS: A cross-sectional study was conducted at three sexually transmitted disease clinics among 1052 Senegalese registered CSWs between 2000 and 2004. Inperson interviews soliciting information concerning demographic characteristics, medical history, sexual behaviour with clients and regular partners, and previous HIV testing history were performed. Blood samples were collected for determination of HIV-1 and/or HIV-2 serostatus. Multivariable, Poisson and log-binomial models were used to calculate prevalence ratios. RESULTS: The overall HIV prevalence was 19.8%. Over 95% of CSWs reported always using a condom with clients, but only 18% reported always using a condom with their regular partners. A history of previous HIV testing was not associated with condom use with clients (adjusted prevalence ratio (APR) = 0.98, 95% confidence intervals, CI: 0.90 to 1.06). However, prior HIV testing was associated with decreased condom use with their regular partners (APR = 0.44, 95% CI: 0.28 to 0.69), especially in women who tested HIV negative (APR = 0.17, 95% CI: 0.08 to 0.36). CONCLUSIONS: CSWs in Senegal have a high HIV prevalence; therefore preventing HIV transmission from this population to the general population is important. Condom use with regular partners is low among registered CSWs in Senegal, and a prior HIV negative test is associated with even less condom use with regular partners. Intervention efforts to increase condom use with regular sexual partners are needed.

Comparison of human immunodeficiency virus (HIV)-specific T-cell responses in HIV-1- and HIV-2-infected individuals in Senegal.

Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting T-cell responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients to determine if differences relate to more efficient HIV-2 control. Homologous HIV-specific T cells were detected in similar frequencies (79% versus 76%, P = 0.7) and magnitude (3.12 versus 3.08 log(10) spot-forming cells/10(6) peripheral blood mononuclear cells) in HIV-1 and HIV-2 infection, respectively. Gag-specific responses predominated in both groups (>/=64%), and significantly higher Nef-specific responses occurred in HIV-1-infected (54%) than HIV-2-infected patients (22%) (P < 0.001). Heterologous responses were more frequent in HIV-1 than in HIV-2 infection (46% versus 27%, P = 0.04), but the mean magnitude was similar. Total frequencies of HIV-specific responses in both groups did not correlate with plasma viral load and CD4(+) T-cell count in multivariate regression analyses. However, the magnitude of HIV-2 Gag-specific responses was significantly associated with lower plasma viremia in HIV-1-infected patients (P = 0.04). CD4(+) T-helper responses, primarily recognizing HIV-2 Gag, were detected in 48% of HIV-2-infected compared to only 8% of HIV-1-infected patients. These findings indicate that improved control of HIV-2 infection may relate to the contribution of T-helper cell responses. By contrast, the superior control of HIV-1 replication associated with HIV-2 Gag responses suggests that these may represent cross-reactive, higher-avidity T cells targeting epitopes within Gag regions of functional importance in HIV replication.

Risk factors for diagnostic subgroups of painful temporomandibular disorders (TMD).

Temporomandibular Disorders (TMD) encompass several entities, which may have differing etiologies. To test this hypothesis, we investigated risk factors for three diagnostic subgroups of painful TMD. Ninety-seven subjects with myofascial pain only, 20 with arthralgia only, 157 with both myofascial pain and arthralgia, and 195 controls without TMD pain met criteria for study eligibility. Investigated risk factors included both physical and psychological variables. Adjusted odds ratios were calculated by multiple logistic regression analyses. Myofascial pain occurring alone was significantly associated with trauma (Odds Ratio [OR] = 2.0), clenching (OR = 4.8), third molar removal (OR = 3.2), somatization (OR = 3.7), and female gender (OR = 4.2). Myofascial pain with arthralgia was significantly associated with trauma (OR = 2.1), clenching (OR = 3.3), third molar removal (OR = 4.0), somatization (OR = 5.1), and female gender (OR = 4.7). No significant associations were found for the small-arthralgia-only group.

HLA class II DR-DQ and increased risk of cervical cancer among Senegalese women.

To examine Senegalese women to confirm and extend associations between HLA class II types and cervical cancer previously observed among African-American, Caucasian, Hispanic, and Japanese ethnic populations, 55 Senegalese women with invasive cervical carcinoma were compared with age-matched (human papillomavirus) HPV-positive (n = 83) and HPV-negative (n = 107) control women. PCR-based HPV and HLA typing methods were used. Data were analyzed using a global randomization test and conditional logistic regression. Although this study failed to confirm a previously reported association between cervical cancer and DQB1*03 alleles, the DRB1*1101-DQB1*0301 haplotype was detected more frequently among cervical carcinoma cases than among controls (adjusted odds ratio, 2.6; 95% confidence interval, 1.0-7.1). Furthermore, as reported by others, we observed a negative association of borderline statistical significance between DRB1*13 and cervical carcinoma (adjusted odds ratio, 0.5; 95% confidence interval, 0.2-1.1). Observations from this study confirm earlier findings of a negative association between DRB1*13 and cervical cancer and suggest that specific DRB1-DQB1 haplotype combinations, rather than individual DQB1*03 alleles, increase the risk for cervical cancer.

Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix.

We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1-14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.

Maternal and neonatal outcomes after induction of labor without an identified indication.

OBJECTIVE: This study was undertaken to examine associations between induction of labor and maternal and neonatal outcomes among women without an identified indication for induction. STUDY DESIGN: This was a population-based cohort study of 2886 women with induced labor and 9648 women with spontaneous labor who were delivered at 37 to 41 weeks' gestation, all without identified medical and obstetric indications for induction. RESULTS: Among nulliparous women 19% of women with induced labor versus 10% of those with spontaneous labor underwent cesarean delivery (adjusted relative risk, 1.77; 95% confidence interval, 1.50-2.08). No association was seen in multiparous women (relative risk, 1.07; 95% confidence interval, 0. 81-1.39). Among all women induction was associated with modest increases in instrumental delivery (19% vs 15%; relative risk, 1.20; 95% confidence interval, 1.09-1.32) and shoulder dystocia (3.0% vs 1. 7%; relative risk, 1.32; 95% confidence interval, 1.02-1.69). CONCLUSION: Among women who lacked an identified indication for induction of labor, induction was associated with increased likelihood of cesarean delivery for nulliparous but not multiparous women and with modest increases in the risk of instrumental delivery and shoulder dystocia for all women.

Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men.

OBJECTIVE: To determine whether combination antiretroviral therapy is associated with reduced detection of HIV-1 RNA and DNA in the anorectal mucosa of men who have sex with men (MSM). DESIGN: Cross-sectional study of 233 MSM recruited from community and clinic sites in Seattle, Washington between July 1996 and December 1997. METHODS: HIV-1 RNA and HIV-1 DNA were detected in anorectal swab specimens by polymerase chain reaction amplification assays. RESULTS: HIV-1 RNA was detected significantly less often in anorectal specimens from users of combination antiretroviral therapies, whether a protease inhibitor was received (15/89; 17%) or not (16/53; 30%), than in men not receiving therapy (43/88; 49%) (P < 0.001, P = 0.03, respectively). In contrast, HIV-1 DNA was detected only slightly less frequently in anorectal specimens obtained from men receiving protease inhibitors (35/81; 43%) or reverse transcriptase inhibitors alone (22/48; 46%) than in specimens from men not receiving therapy (45/78; 58%) (P = 0.07, P = 0.20, respectively). Among men with < 50 copies HIV-1 RNA/ml plasma, detection of HIV-1 RNA in anorectal specimens was rare (1/54; 2%) but detection of HIV-1 DNA was common (14/50; 28%). CONCLUSIONS: Combination antiretroviral therapy is associated with reductions in HIV-1 RNA, but HIV-1 DNA remains detectable in the anorectal canal of almost half of MSM receiving such therapy. Condom use during anal intercourse should be encouraged, regardless of plasma viral load response to potent antiretroviral therapy.

Secretor polymorphism and human immunodeficiency virus infection in Senegalese women.

The FUT2 gene encodes the enzyme alpha (1,2) fucosyltransferase, which determines expression of blood-group antigens on mucosal epithelial cell surfaces and in secretions. Homozygotes for a specific stop mutation in FUT2 (nonsecretors) cannot produce this enzyme and thus are unable to express blood group antigens. Nonsecretor status is associated with a decreased risk of several respiratory viral infections. By use of molecular genotyping, 2 populations of Senegalese women were examined for polymorphisms of the FUT2 gene. Among Senegalese commercial sex workers, absence of FUT2 (nonsecretor genotype) was associated with reduced risk of human immunodeficiency virus (HIV) type 1 infection (odds ratio [OR] adjusted for cervical and vaginal infection, 0.18; 95% confidence interval [CI], 0.04-0.90) and HIV-2 infection (adjusted OR, 0.43; 95% CI, 0.13-1.39), although the latter was not statistically significant. Modification of cell surface carbohydrates at mucosal surfaces determined by the FUT2 gene may underlie the protective association against heterosexual HIV infection.

Risk factors for urinary tract infection in the postpartum period.

OBJECTIVE: We sought to examine risk factors for urinary tract infection in postpartum women. STUDY DESIGN: Subjects (n = 931) with maternal urinary tract infections and control subjects (n = 1862) were identified by using a linked Washington State birth certificate and Birth Events Records Database for the years 1987-1993; stratified analysis was performed by using Mantel-Haenszel procedures. RESULTS: Increased risk for postpartum urinary tract infection was associated with black, Native American, or Hispanic race-ethnicity (odds ratio, 1.30; 95% confidence interval, 1.03-1.64) and unmarried status (odds ratio, 1.33; 95% confidence interval, 1.11-1.58). Cesarean delivery (odds ratio, 2.70; 95% confidence interval, 2.27-3.20) and tocolysis (odds ratio, 3.30; 95% confidence interval, 2.15-5.06) also contributed to maternal risk of acquiring a urinary tract infection. Maternal risk factors included renal disease (adjusted odds ratio, 3.89; 95% confidence interval, 1.80-8.41) and preeclampsia-eclampsia (adjusted odds ratio, 3.21; 95% confidence interval, 2.36-4.38). Among women undergoing vaginal delivery, renal disease (odds ratio, 5.47; 95% confidence interval, 2.04-14.64) and abruptio placentae (odds ratio, 5.02; 95% confidence interval, 1.84-13.64) were risk factors. Length of hospital stay was significantly associated with urinary tract infection. CONCLUSION: Maternal medical conditions and procedures that predispose to urinary tract infections are those that also are associated with urethral catheterization. In addition, maternal urinary tract infections may contribute significantly to duration of postpartum hospital stay.

Characterization of ciliary activity in distal Fallopian tube biopsies of women with obstructive tubal infertility.

Biopsy specimens were obtained from the distal end of the Fallopian tubes of 62 women with tubal infertility and examined by light and electron microscopy. Ciliary beat frequency (CBF) measurements were obtained using laser light spectroscopy. Neither demographic nor behavioural characteristics nor serological evidence of past chlamydial infection were associated with CBF measurements. In contrast, CBF were significantly lower (P < 0.05) in tissues with oedema compared to tissues without oedema (6.7 versus 12.9) and in tissues with erythema compared to tissues without erythema (9.2 versus 13.7). Furthermore, CBF measurements did vary by chlamydial serotype pattern, with lower values observed among the tissues of women with antibodies to serotype C or E (without D) as compared to the tissues of women with other serotypes (P < 0.04). However, these data must be interpreted with caution as the numbers of subjects with chlamydial antibodies to serotype C (n = 3) or E without D (n = 5) were few in number and serotyping of IgG antibodies in blood is not as accurate as it is in bacterial isolates. Confirmation of the suggested association between chlamydial serotype and risk of adverse sequelae could indicate potential new avenues for vaccine research.

Risk of anal carcinoma in situ in relation to human papillomavirus type 16 variants.

Infection with human papillomavirus (HPV), especially HPV16, is central to the development of squamous anogenital cancers and their precursor lesions, termed "squamous intraepithelial neoplasias." Men who have sex with men, particularly those who are infected with HIV, are at a high risk for anal infection with HPV16 and for low-grade anal neoplasia; however, only a subset of these men develop anal invasive cancer or its immediate precursor lesion, anal carcinoma in situ (CIS). To examine the hypothesis that certain variants of HPV16 are most strongly associated with development of anal CIS, we followed 589 men who have sex with men whose initial anal cytological smears did not show anal CIS. Anoscopy, anal cytology, and PCR-based assays for detection and classification of HPV types were performed every 4-6 months, with HPV16 further classified by single-stranded conformation polymorphism analysis as being a prototype-like (PL) or non-prototype-like (NPL) variant. Anal CIS was histologically confirmed in 6 of 384 (1.6%) consistently HPV16-negative men, in 12 of 183 (6.6%) men with HPV16 PL variants, and in 4 of 22 (18.2%) men with HPV16 NPL variants. After adjustment for anal cytological diagnoses at study entry, HIV status and CD4 count, and detection of HPV types other than type 16, men with HPV16 NPL variants were 3.2 times (95% confidence interval, 1.0-10.3) more likely to develop anal CIS than were those with PL variants. Neither detection of HPV16 DNA at high levels nor detection of HPV16 DNA for a prolonged period, factors that we previously demonstrated to be associated with risk of high-grade anal squamous intraepithelial neoplasia, was significantly associated with HPV16 NPL variants. The biological mechanism relating to Ihis excess risk remains undetermined.

Effect of HIV infection on the natural history of anal human papillomavirus infection.

OBJECTIVE: To identify risk factors for the detection of prevalent and incident anal human papillomavirus (HPV) infection, and HPV persistence among HIV-seropositive and seronegative homosexual men. DESIGN: Longitudinal study of 287 HIV-seronegative and 322 HIV-seropositive men attending a community-based clinic. METHODS: Subjects underwent an interview and examination; specimens were collected for HIV serology and assessment of anal HPV and HIV DNA. RESULTS: Anal HPV DNA was detected at study entry in 91.6% of HIV-infected men, and 65.9% of men not infected with HIV. HPV detection was associated with lifetime number of sexual partners and recent receptive anal intercourse (HIV-seronegative men), decreased CD4+ lymphocyte count (HIV-seropositive men), and anal warts (all men). Among men negative for HPV at study entry, subsequent detection of HPV was associated with HIV, unprotected receptive anal intercourse, and any sexual contact since the last visit. Among men positive for HPV at study entry, subsequent detection of additional HPV types was more common among HIV-seropositive men. Becoming HPV negative during follow-up was less common among men with HIV or high HPV levels at study entry. Among those with HIV, HPV persistence was associated with presence of anal HIV DNA, but not with CD4+ lymphocyte count. CONCLUSIONS: Risk of anal HPV infection appears to increase with sexual exposure, epithelial trauma, HIV infection and immune deficiency. Incident infection may result from recent sexual exposure or reactivation of latent infection. Further studies are needed to elucidate the mechanism by which HIV DNA in the anal canal increases the risk of HPV persistence.

Determinants of human immunodeficiency virus DNA and RNA shedding in the anal-rectal canal of homosexual men.

To define the determinants of anal-rectal shedding of human immunodeficiency virus (HIV) DNA and RNA, 374 HIV-seropositive homosexual men were tested. Factors independently associated with detection of anal-rectal HIV DNA included anal-rectal inflammation and detection of anal human papillomavirus DNA; predictors of HIV RNA included detection of anal-rectal HIV DNA, anal-rectal inflammation, and high plasma HIV RNA levels. The latter (>10,000 copies/mL) was the main determinant of anal-rectal HIV RNA shedding when HIV DNA (e.g., HIV-infected cells) was not detected in the anal-rectal sample. The local presence of HIV-infected cells and local inflammation were the principal determinants of HIV RNA among those with low (<10,000 copies/mL) plasma HIV RNA load. Among those with anal-rectal HIV DNA present, increased HIV RNA plasma load did not increase the risk of shedding of HIV RNA into the anal-rectal canal.

The effect of health maintenance organization vs commercial insurance status on obstetrical management and outcome.

OBJECTIVE: To compare obstetrical management and birth outcomes between patients with health maintenance organization (HMO) insurance and those with private commercial insurance. DESIGN: Retrospective population-based cohort study. SETTING: King County, Washington. PATIENTS: Among newborns delivered in 1992 and 1993, a random sample of 4000 birth records listing HMO insurance for prenatal care was compared with a random sample of 4000 birth records listing private commercial insurance as the primary coverage. MAIN OUTCOME MEASURES: Use of ultrasonography and amniocentesis; rate of primary cesarean section performed; adequacy of prenatal care; incidence of maternal medical complications, low birth weight, and congenital malformations; and length of hospital stay. RESULTS: Women covered by HMO compared with commercial insurance were more likely to undergo ultrasonography (relative risk [RR], 1.4; 95% confidence interval [CI], 1.3-1.4). Inadequate prenatal care was less frequent among HMO-insured patients (RR, 0.6; 95% CI, 0.5-0.7), as was the incidence of birth weight below 2500 g (RR, 0.7; 95% CI, 0.6-0.9). No differences in rates of cesarean section and congenital anomalies were observed. Among women without obstetrical risk factors, HMO-insured mothers were at an increased risk of labor and delivery complications (RR, 1.4; 95% CI, 1.3-1.5); their infants were at an increased risk of infant distress (RR, 1.8; 95% CI, 1.5-2.2). CONCLUSIONS: Patients with HMO insurance have improved access to prenatal care and screening when compared with privately insured patients. The reasons for increased risks of abnormal maternal and infant outcomes observed among a subset of HMO-insured patients are unclear. A study with more detailed prospective data collection is warranted.

Periodontal status of HIV-1 and HIV-2 seropositive and HIV seronegative female commercial sex workers in Senegal.

Comprehensive studies of 92 commercial sex workers in Senegal, Africa included an oral examination in which we obtained measurements of decayed, missing, and filled (DMF) teeth; plaque index; gingival index; recession; probing depth (PD); clinical attachment loss (CAL); and the presence of HIV-associated periodontal lesions, under conditions wherein the examiner was unaware of the subject's HIV status. Twenty-seven subjects (29%) were HIV seropositive, 19 of whom were positive for HIV-1, 7 positive for HIV-2, and 1 positive for both. Most subjects were not taking any medications and previous dental care was limited. HIV-seronegative and HIV-seropositive subjects were similar in mean age, number of DMF teeth, percentage of sites with visible plaque, and number of sites with recession. However, the frequency of sites with gingival bleeding, with PD > or = 6 mm, and with CAL > or = 6 mm was significantly greater in seropositive than seronegative subjects. No differences were observed between HIV-1 and HIV-2 positive subjects. About 26% of HIV-seropositive subjects and about 5% of the seronegative subjects exhibited at least one site with concurrent PD > or = 6 mm and CAL > or = 6 mm. HIV-associated periodontal lesions were seen in 3 HIV-seropositive subjects (2 linear gingival erythema, 1 necrotizing periodontitis). One HIV-seronegative subject exhibited necrotizing gingivitis. In this population with multiple risks to oral health, both HIV-1 and HIV-2 infections were associated with a significantly increased prevalence of periodontal disease.

Seroprevalence of human papillomavirus types 6 and 16 capsid antibodies in homosexual men.

Human papillomavirus (HPV) has been implicated in the pathogenesis of anal carcinoma, which is increased in homosexual men. Little is known about the serologic response to HPV in normal or immunosuppressed men; therefore, HIV-infected and -uninfected homosexual men were screened for HPV-6 and -16 capsid antibodies. HIV-infected men had increased HPV DNA detection but did not significantly differ in the prevalence of serum HPV antibodies. HPV-6 DNA detection and the presence of anal warts were significantly correlated with serum antibody overall and in the HIV-infected subgroup. HPV-16 DNA detection was not significantly correlated with serum antibody overall or in either subgroup; however, HIV-infected men with high-grade anal squamous intraepithelial lesions were significantly more likely to have HPV-16 antibodies. HIV-infected men are able to generate an antibody response to HPV, and a lack of serum HPV antibodies cannot explain the increased HPV-associated disease seen in HIV-infected men.

Detection of human immunodeficiency virus type 1 and type 2 in the female genital tract: implications for the understanding of virus transmission.

Risk of perinatal or female to male sexual transmission of HIV is likely to be associated with whether, and at what concentration, the virus is present in the cervical and vaginal secretions of the HIV-infected woman. Examining correlates of cervical and vaginal HIV shedding is, therefore, essential for the development of strategies to interrupt HIV transmission. This article presents the rationale for using detection of HIV in the female genital tract as a marker of infectivity, and briefly describes methods for detecting HIV-1 and HIV-2 in cervical or vaginal fluids. Findings from studies incorporating the measurement of HIV in the female genital tract are reviewed, placing particular emphasis on issues relevant to epidemiological studies of HIV transmission.

HIV-1, HIV-2, human papillomavirus infection and cervical neoplasia in high-risk African women.

OBJECTIVE: To determine the effect of HIV-1 and HIV-2 infection on the prevalence of cervical human papillomavirus (HPV) and squamous intraepithelial lesions (SIL) in a population of high-risk women in Senegal. DESIGN AND PARTICIPANTS: Cross-sectional study among 759 female commercial sex workers, including 68 with HIV-1, 58 with HIV-2, 14 with HIV-1 and 2, and 619 without HIV infection. RESULTS: Overall, HPV was detected in 43% of women by polymerase chain reaction (PCR), and in 7% by Southern transfer hybridization, with 7.4% of all women having SIL. The mean CD4 count was 820, 1205, and 727 x 10(6)/l for those with HIV-1, HIV-2, and dual HIV-1 and 2 infections, respectively, and 1447 x 10(6)/l for those without HIV infection. Both HIV-1 and HIV-2 were associated with HPV, as detected by PCR [HIV-1 odds ratio (OR), 2.9; 95% confidence interval (Cl), 1.7-4.9; HIV-2 OR, 1.7; 95% Cl, 1.0-2.9]. HIV-2 was also associated with cervical SIL, and although the association between HIV-1 and SIL did not attain statistical significance, a trend was apparent (HIV-1 OR, 1.8; 95% Cl, 0.7-4.7; HIV-2 OR, 2.9; 95% Cl, 1.2-7.2). CONCLUSIONS: Despite less immunosuppression with HIV-2, both HIV-1 and HIV-2 were associated with detection of HPV. HIV-2 was also associated with SIL. Further studies are needed to examine the risks of high-grade SIL and invasive cervical cancer with HIV-1 versus HIV-2 infection.

PIP: Between February 1990 and March 1993, 759 female commercial sex workers who attended sexually transmitted disease (STD) clinics in Dakar, Thies, and Mbour, Senegal, were interviewed and underwent a general physical and detailed gynecologic examination so researchers could ascertain the influence of HIV-1 and HIV-2 infection on the prevalence of cervical human papillomavirus (HPV) and squamous intraepithelial lesions (SIL) in this high-risk population. Most lesions were low-grade SIL. 619 had neither HIV-1 nor HIV-2 infection. 9%, 8%, and 2% had HIV-1, HIV-2, and concurrent HIV-1 and HIV-2 infection, respectively. Polymerase chain reaction revealed that 43% had HPV infection, while Southern transfer hybridization found only 7%. HIV-1 infected women faced a significant increased risk for HPV (adjusted odds ratio [AOR] = 2.9) as also did HIV-2 infected women (AOR = 1.7). Both these groups also faced an increased risk for SIL (AOR = 1.8 and 2.9, respectively), but the increased risk was not significant. Similarly, women infected with both HIV-1 and HIV-2 faced an increased risk of HPV and SIL (AOR = 4.9 and 5.2, respectively). Among women with HIV infection, women with HPV had a lower CD4 count and CD4/CD8 ratio (854 vs. 1033 million/l, p = 0.08, and 0.88 vs. 1.17, p = 0.05, respectively) than women with no detectable HPV. HIV-positive women with SIL had a lower CD4/CD8 ratio than HIV-positive women without SIL (0.65 vs. 1.03; p = 0.003). HIV-2 women exhibited lower immunosuppression than HIV-1 women. These findings show that both HIV-1 and HIV-2 infection were associated with HPV and SIL. The researchers expressed interest in longitudinal studies designed to examine the risk of high-grade SIL, the direct precursor of invasive cervical cancer, among HIV-infected women.