Sex and the course of HIV infection in the pre- and highly active antiretroviral therapy eras

We reviewed the available literature on the potential effects of sex on the course of HIV infection and found that there is little evidence for sex differences in the rate of disease progression in the pre-highly active antiretroviral therapy (HAART) and HAART era. Compared to men, women appeared to have lower HIV RNA levels and higher CD4 cell counts shortly after infection with HIV, but studies were inconclusive regarding whether these differences diminish over time. Differences in viral load or CD4+ cell count might cause women to delay initiation of HAART. Nonetheless, we found no substantial sex difference in the benefit of antiretroviral therapy. The studies we reviewed failed to find any harmful effect of pregnancy on HIV disease progression. With the availability of effective antiretroviral agents, HIV-infected women have increasingly decided to have children. Conflicting results exist on the effect of HAART on regression of cervical intra-epithelial neoplasia (CIN). Unlike CIN, invasive cervical cancer has not been found to be much higher in HIV-infected women than in HIV-uninfected women. Although publication bias cannot be ruled out, published studies suggest higher rates of adverse events among HIV-infected women on therapy as compared to men. As more pharmacological agents are developed, it is especially important that potential sex differences in pharmacodynamics are assessed. The relationship between metabolic abnormalities, changes in body habitus, and endocrine perturbations has not been extensively studied. Whether sex differences are due to unalterable genetic factors or social and environmental conditions, it is imperative that all HIV-infected individuals have equal access to interventions that can slow disease progression.     

Factors predicting the persistence of genital human papillomavirus infections and PAP smear abnormality in HIV-positive and HIV-negative women during prospective follow-up

As part of an extensive multi-institutional DIANAIDS study focused on assessing the risk factors, natural history, diagnosis and follow-up of genital human papillomavirus (HPV) infections in HIV-infected women, the present communication reports a sub-cohort of 142 women (89 HIV+ and 48 HIV-), followed-up for a mean of 14.07 (+/-10.84) months to analyse the factors predicting the persistence and clearance of HPV infections (polymerase chain reaction [PCR] and sequencing) and cervical Papanicolaou (PAP) smear abnormalities, using both univariate (Kaplan-Meier) and multivariate (Cox) survival analysis. The appearance of new HPV infections during the follow-up was significantly more frequent in HIV-positive than in HIV-negative women, odds ratio (OR) 8.800 (95% confidence interval [CI]: 1.199-64.611), and also the clearance rate was significantly less frequent in HIV-positive than in HIV-negative women, 69.2% vs 22.8%, respectively (OR 0.330; 95% CI: 0.163-0.670). These two groups were also markedly different with respect to the clinical course of the cervical lesions, in the frequency of progressive disease (determined by PAP smear) was higher in HIV-positive group (12/89) than in HIV-negative women (2/52) (OR 3.506; 95% CI 0.816-15.055) (P = 0.055), in whom the disease regressed more frequently than in HIV-positive women (13.5% vs 7.9%) (OR 0.584; 95% CI 0.217-1.573). Using (1) HPV-positivity, (2) oncogenic HPV-type and (3) significant PAP smear abnormality at the end of follow-up as outcome measures, (1) was significantly (P < 0.001) predicted by the following variables in univariate analysis: age, mode of contraception, CD4 count, and HIV-positivity. The significant predictors of (2) were age and mode of contraception. The outcome measure (3) was significantly predicted by CD4 count, PAP smear abnormality and PCR status at entry. In the multivariate analysis, the significant independent predictive factors for HPV-positivity proved to be only the HIV status (P < 0.001), and PCR status at entry, p53 polymorphism at aa-72, oncogenic HPV type and significant PAP smear at entry remained independent predictors, with the significance level of P < 0.05. None of the significant predictors of oncogenic HPV type in univariate analysis retained their independent value in multivariate analysis. Oncogenic HPV type at entry proved to be an independent predictor of significant PAP smear (P < 0.05). The present results indicate that HIV-infected women, even on highly active antiretroviral therapy, demonstrate a more aggressive clinical course of cervical HPV infections, and fail to eradicate the disease more frequently than HIV-negative women. This persistence of HPV-positivity, oncogenic HPV type and significant PAP smear abnormality can be predicted by the results of PAP test and HPV typing in univariate analyses, and partly retain their independent predictive value also in multivariate analysis. Clearly, in addition to regular monitoring by PAP smear, HPV testing for the oncogenic HPV types seems to provide additional prognostic information in the management of cervical lesions in HIV-infected women.     

The impact of HIV status and type on the clearance of human papillomavirus infection among Senegalese women

BACKGROUND: Persistent infection with human papillomavirus (HPV) is associated with the development and progression of HPV-related disease, including cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. METHODS: We examined the impact of human immunodeficiency virus (HIV) status and type on the clearance of HPV infection among 614 Senegalese women enrolled in a longitudinal study of HPV and CIN. Women were examined every 4 months for HPV DNA. Clearance was defined as 2 consecutive negative HPV DNA test results. RESULTS: Cox proportional hazard regression with time-dependent covariates indicated that HIV-positive women were less likely to clear HPV infection (adjusted hazard ratio [HR], 0.31 [95% confidence interval {CI}, 0.21-0.45]) than HIV-negative women. Among HIV-positive women, those with CD4 cell counts <200 or from 200 to 500 cells/microL showed a 71% (adjusted HR, 0.29 [95% CI, 0.11-0.76]) and 32% (adjusted HR, 0.68 [95% CI, 0.31-1.48]) reduction in the likelihood of HPV clearance, respectively, compared with those with CD4 cell counts >500 cells/microL. HIV-2 infection was associated with an increased likelihood of HPV clearance (adjusted HR, 2.46 [95% CI, 1.17-5.16]), compared with that for HIV-1 infection. CONCLUSIONS: HIV infection reduces the likelihood of HPV clearance. Among HIV-positive women, immunosuppression, as measured by CD4 cell count, reduces the likelihood of HPV clearance, and HIV type appears to be associated with HPV clearance.     

Evolution of cervical cytologic changes among HIV-infected women with normal cytology in the HAART era

The influence of HAART on the evolution to cervical squamous intraepithelial lesions (SIL) among HIV(+) women with a normal cytological test in the HAART era was studied. A retrospective cohort study (1997-2005) of HIV-infected women treated with HAART was conducted. Those with a normal cervical cytology (Papanicolaou test) and at least one subsequent test were included. Survival (time until diagnosis of SIL), univariate, and multivariate analyses were performed. A total of 133 HIV-infected patients treated with HAART were included. The incidence of SIL was 35% (47 patients). SIL was diagnosed in 36 of 110 (33%) patients with a baseline and final immunological status of >200 CD4 cells/microl and in 6 of 9 (67%) patients with a baseline and final immunological status of < or =200 CD4 (OR: 0.24, 95% CI: 0.06-1.03, p = 0.041). SIL was diagnosed in 10 of 60 (17%) patients with an undetectable baseline and final HIV viral load and in 36 of 70 (51%) patients with a detectable HIV viral load (OR: 0.19, 95% CI: 0.07-0.46, p < 0.001). A high incidence of SIL (cancer precursor lesions) was observed among HIV(+) women without a background of cervical pathology. The effect of HAART on the control of HIV replication and of immunological status (>200 CD4) through the follow-up was associated with a reduction of SIL.     

Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.     

Prevalence and risk factors for cervical intraepithelial neoplasia among HIV-infected women

ObjectivesTo evaluate the prevalence and the risk factors for cervical intraepithelial neoplasia (CIN) among HIV-infected women.MethodsCross-sectional study of 494 HIV-infected women in Brazil, between 1998 and 2008. Gynecologic exam was performed, and samples were collected for cervical cytology and for HPV DNA detection. Cervical biopsy was carried out when indicated. HPV infection, CD4 T-lymphocyte count and HIV viral load were compared with cervical histopathology. Univariate and multivariate statistical analyses were performed to evaluate the statistical association of several risk factors.ResultsCIN prevalence detected by histopathology was 23.4% (6% of CIN2/3 and 17.4% cases of CIN1). Multivariate analysis confirmed an independent association of CIN with CD4 T-lymphocyte count below 200 cells/mm³ (OR 5.0, 95% CI 2.5–10.1), with a positive detection of HPV DNA (OR 2.0, 95% CI 1.2–3.5), and with age ≤ 34 years old (OR 1.5, 95% CI 1.0–2.4). HIV viral load and antiretroviral use were not independent risk factors for CIN.ConclusionsSeverity of immunosupression, presence of HPV infection and younger age are strong predictors of CIN among HIV-infected women.     

Determinants and evolution of squamous intraepithelial lesions in HIV-infected women, 1991-2004

This study presents a case-control nested analysis of cervical squamous intraepithelial lesions (SIL) in a cohort of 423 HIV-infected women with registered Pap smears between 1991 and 2004. Data on Pap smear results, CDC HIV classification, CD4 cell count and antiretroviral therapy were prospectively collected. Pap smears were classified using the Bethesda classification. Women had a median of three Pap smears registered in the database. The first Pap smear was registered 相似文献   

Association of vitamin A deficiency with cervical squamous intraepithelial lesions in human immunodeficiency virus-infected women

To explore the relationship between vitamin A (retinol) deficiency and cervical squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women, we measured serum retinol concentrations in 1314 women enrolled in the Women's Interagency HIV Study and correlated the results with concurrent cervical cytology. At the baseline visit, 204 (15.5%) of the 1314 patients had retinol concentrations consistent with deficiency (<1.05 micromol/L). Analysis of Papanicolaou smears showed SILs in 216 (16.4%) of 1314 women. Cervical SILs were found to be associated with retinol concentrations <1.05 micromol/L (multivariate odds ratio [OR], 1.63; P=.04) in a multivariate model, which included human papillomavirus (HPV) status and markers of nutritional status and HIV disease stage. In the subset of women with genital HPV (n=774), a multivariate analysis again revealed a significant independent association between retinol <1.05 micromol/L and cervical SILs (multivariate OR, 1.75; P=.02). Our findings suggest that retinol deficiency may contribute to the development of cervical SILs in HIV-infected women.     

Short-term follow up of cervical squamous intraepithelial lesions associated with HIV and human papillomavirus infections in Africa.

A prospective study in gynaecology clinics was conducted in Abidjan, C?te d'Ivoire, to assess the short-term evolution of squamous intraepithelial lesions (SILs). Of 94 women with a cytological diagnosis of SIL, 38 were infected with HIV. The average follow-up period after the initial smear was 5 months. Detection of human papillomavirus (HPV) by polymerase chain reaction (PCR) was performed at both the time of enrolment and final follow-up smear. There were 39 cases of persistent SILs. HIV-positive women had a higher percentage of persistent SIL (76%) than HIV-negative women (18%, relative risk (RR)=4.3, 95% confidence interval (CI) = 2.4, 7.7). SILs were more frequent among women infected with HPV at the time of enrolment or with persistent HPV infection, but these associations disappeared after adjusting for HIV serostatus. Spontaneous regression of SILs commonly occurs in HIV-negative African women. HIV-infected women with cervical dyskaryosis require gynaecology follow-up.     

Change in patterns of HIV status disclosure in the HAART era and association of HIV status disclosure with depression level among women

Whether widespread use of HAART changed patterns of HIV status disclosure among women living with HIV is largely unknown. In addition, the association between time to first HIV disclosure and depression has not been fully explored among women. A retrospective cross-sectional survey was conducted among HIV-infected women from the Washington, DC site of the Women’s Interagency HIV Study to collect detailed information about their HIV status disclosure behavior. A sample of 202 HIV-positive women, 102 diagnosed prior to and 100 post-HAART era participated in this study. Relationships between treatment era when diagnosed (pre-HAART or HAART era) and patterns of HIV status disclosure, and associations between HIV status disclosure and depression level were examined using generalized linear regression models with generalized estimating equation to adjust for repeated measurements from the same individuals. Our analyses showed that treatment era was not associated with either comfort level of HIV status disclosure or time to first HIV disclosure to either family members or friends. However, women were less likely to disclose HIV status to their family members in the HAART era (P?=?0.006) after adjusting for social network type, comfort level of disclosure, time to first disclosure and length of follow-up time. In addition, longer time to first HIV disclosure, but not comfort level or extent of HIV status disclosure, was independently associated with depression levels as measured by CES-D score at study enrollment (“a few months after” vs “within a few days”: P?=?0.008). More definitive studies utilizing longitudinal designs should be conducted to further examine impact of HAART era on HIV status disclosure and effect of HIV status disclosure on mental health.     

Risk factors, diagnosis and prognosis of cervical intraepithelial neoplasia among HIV-infected women

The prevalence of cervical intraepithelial neoplasia (CIN) is high among HIV-infected women. Decreased CD4 lymphocytes, high human immunodeficiency viral load (HIVL) and human papillomavirus (HPV) infection are risk factors for CIN. We characterized the prevalence, risk factors and prognosis of histologically-verified CIN among systematically followed HIV-infected women enrolled from a low HIV-prevalence population. The study population comprised 153 HIV-infected women followed between 1989 and 2006. The mean +/- SD duration of follow-up was 5.6 +/- 3.8 years. Demographic as well as treatment-related data were derived from medical reports. During the follow-up, 51 subjects (33%) displayed CIN (16% CIN 1 and 18% CIN 2 +), whereas 102 subjects had Pap smear results of normal cells, atypical squamous cells of uncertain significance, or signs of low-grade squamous intraepithelial lesion (LSIL) but no CIN in histological specimens from the cervix. Only one case of cancer of the uterine cervix was detected. Pap smears were reliable in screening for CIN; 75% of patients with CIN had high-grade squamous intraepithelial lesion (HSIL) or LSIL in Pap smears taken at the time of dysplasia. The incidence of CIN decreased from 12.7 to 3.5 (per 100 subjects) between 2000 and 2005 (P = 0.07). The risk of CIN was not associated with decreased levels of CD4 lymphocytes, duration of HIV infection, use of antiretroviral medication or plasma HIVL. In univariate analysis, bacterial vaginosis (BV) was associated with a significantly increased risk of CIN, whereas parity was associated with lower risk of CIN. Each delivery lowered the risk of CIN by 30% (P = 0.02). The significantly lower risk of CIN among parous women (P = 0.04) persisted in multivariate analysis. CIN was treated by means of loop electrosurgical excision procedure (LEEP), (n = 34). The recurrence rate was low; seven subjects (14%) had a recurrence of CIN during follow-up. The nadir of CD4 lymphocytes was lower (P = 0.04) and the HIVL higher (P = 0.03) among subjects with recurrence of CIN. Duration of HIV infection, use of antiretroviral medication and positive margins in LEEP specimens were indistinguishable among subjects with vs. without recurrence of CIN. The prevalence of CIN is high among systematically managed HIV-infected women. However, the incidence of CIN decreased during the 21st century. BV was associated with an increased risk of CIN whereas parous women had lower risk of CIN. However, the patients with and without CIN could not be distinguished on the basis of previously described risk factors. Regular follow-up by means of Pap smears is warranted in all HIV-infected women.     

Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality

BACKGROUND: Kidney disease is an increasingly important complication of HIV. OBJECTIVES: To examine the incidence and predictors of acute renal failure before and after the introduction of HAART, and the impact of acute renal failure on in-hospital mortality in the post-HAART era. METHODS: Adults hospitalized in acute care hospitals in New York State during 1995 (pre-HAART) or 2003 (post-HAART) were identified from the state Planning and Research Cooperative System database. HIV status was defined by primary or secondary diagnosis code. The impact of HIV and HAART on the incidence of acute renal failure and mortality, and the impact of acute renal failure on mortality, was assessed using chi analysis and multivariate regression. RESULTS: There were 52,580 HIV-infected patients discharged from hospital in 1995 and 25,114 in 2003. Compared with uninfected patients, HIV-infected patients had an increased incidence of acute renal failure in both the pre-HAART [adjusted odds ratio (OR), 4.62; 95% confidence interval (CI), 4.30-4.95] and post-HAART eras (adjusted OR, 2.82; 95% CI, 2.66-2.99). In the post-HAART cohort, acute renal failure was associated with traditional predictors such as age, diabetes mellitus, and chronic kidney disease, as well as acute or chronic liver failure or hepatitis coinfection (P < 0.001 for all comparisons). Acute renal failure was associated with mortality among HIV-infected patients in the post-HAART era (OR, 5.83; 95% CI, 5.11-6.65). CONCLUSIONS: Acute renal failure remains common among hospitalized patients with HIV and is associated with chronic kidney disease, liver disease, and increased mortality.     

Highly active antiretroviral therapy and cervical intraepithelial neoplasia

Highly active antiretroviral therapy (HAART) has improved HIV prognosis, but its effect on cervical intraepithelial neoplasia (CIN), which is associated with HIV, is uncertain. Among 71 HAART-treated women the prevalence of CIN before HAART was 55%. After a median of 10 months after starting HAART the prevalence had increased to 62% (P = 0.20); 13% of patients experienced regression of a CIN lesion, and this was most strongly associated with a greater increase in CD4 cell count. Such studies will provide the basis for guidelines for monitoring CIN in HIV-positive women in the HAART era.     

The social epidemiology of HIV transmission among African American women who use drugs and their social network members

Despite 15 years of prevention efforts, recent increases in HIV infection have been documented for Black women in the US. Little is known about the role played by HIV status disclosure in high HIV prevalence communities. 180 Black women who used drugs in the past 30 days were recruited between May 2002 and May 2004 in New York City. Women were administered a structured network questionnaire and HIV serotested. Risk practices, HIV status disclosure within networks and mixing patterns by known HIV status are examined. Most (85%) women had used crack in the past 30 days; 48 (27%) had injected drugs, 65 (36%) reported anal sex, and 99 (55%) reported sex work at some time. Forty (22%) women were HIV-seropositive; 29 (16%) knew their seropositive status. Of high risk individual behaviours, only a history of sex work was associated with an HIV-seropositive status [(aOR=3.0; 95%CI: 1.3-7.3), p=.01]. Few (7%) of 600 network members disclosed an HIV positive status, although 73% were sex or drug use partners. Women who knew themselves to be HIV-infected were more likely than other women to report HIV-infected network members [(OR=1.5; 95%CI: 1.1-6.4), p=.03]. However, only 51% of network members disclosed an HIV status and women disclosed to 50% of their network members. In a context of high background HIV prevalence and low levels of HIV status disclosure, serodiscordant mixing patterns likely facilitate transmission.     

Sexually transmitted infections among women living with HIV in a Brazilian city

BackgroundClinical improvements following highly active antiretroviral therapy (HAART) may increase high-risk behaviors resulting in sexually transmitted infections (STI). Optimism related to the success of HAART in slowing disease progression, reducing viral load, and improving health status might be important factors for increasing sexual risk behaviors such as less use of condoms.ObjectiveTo determine the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, syphilis, hepatitis B and C, high-risk HPV, and cervical cytological abnormalities among women living with HIV (WLHIV) who attended a Reference Center for STI/AIDS in Brazil.MethodsA cross-sectional study was conducted among 151 WLHIV attending an STI Clinic in Vitória city, Brazil. A structured questionnaire, including demographic, behavioral, and clinical information, was used for data collection. Serological tests for HIV, syphilis, hepatitis C and B, CD4 counts, and viral load determination were performed. Cervical samples were collected for cytology and real-time PCR for HPV,Chlamydia, and Neisseria gonorrhoeae.ResultsIn this study, 59% of women had at least one diagnosed STI at the time of the first clinic visit; 31% had clinical forms of anogenital HPV, 10% syphilis, 8%Neisseria gonorrhoeae, 5.0% trichomoniasis, 3% Chlamydia trachomatis, 1% hepatitis B, and 1% hepatitis C; 6.7% of the women presented with cervical cytological abnormalities. Furthermore, 46.3% of women had HR-HPV, and 17.6% had HPV 16/18. Only 5% of the women had a CD4 count <200 cells/mm³, 61.6% had undetectable HIV viral load, and 81.3% were currently on HAART.ConclusionA high prevalence of STI and HR-HPV infections were observed among HIV-infected women in this investigation. Prevention programs need to focus on counseling WLHIV and their regular partners with focused interventions such as couples counseling and education programs.     

Uniform risk of clinical progression despite differences in utilization of highly active antiretroviral therapy: Swiss HIV Cohort Study

OBJECTIVE: To compare the initiation of highly active antiretroviral therapy (HAART) in HIV-infected patients according to sex, route of HIV acquisition and education, and to assess the impact of differences in utilization on the probability of progression to AIDS. DESIGN AND SETTING: Swiss HIV Cohort Study, a national prospective multi-centre study. PARTICIPANTS: A total of 3342 patients, including 1007 (30%) women. HIV was acquired through injection drug use in 1155 (35%) cases and through sex between men in 1172 (35%). Twenty-eight per cent (957) of participants had attained only the minimum level of schooling. At baseline, the median CD4 cell count was 269x10(6)/l cells, median HIV-1 RNA was 4.3 log10 copies/ml and 2917 (87%) were free of AIDS. METHODS: Kaplan-Meier life tables and Cox proportional hazards regression. RESULTS: During 7007 person-years of follow-up 2285 (69%) patients started HAART and 318 (10%) developed a new AIDS event. In multivariable analysis controlling for CD4 cell count, viral load and disease stage at baseline, the probability of starting HAART was lower in injection drug users compared with men who have sex with men, hazard ratio 0.63 (95% confidence intervals 0.56-0.70) and in patients with minimum schooling compared with those with vocational training, hazard ratio 0.82 (0.75-0.91). The risk of progression to AIDS was similar among men and women, patients with a history of injecting drug use, and patients with lower educational attainment in both univariable and multivariable analysis. CONCLUSION: HIV-infected injecting drug users and those with lower levels of educational attainment start HAART later than other patient groups. The deferred initiation of therapy in these patients does not, however, appear to translate into an increased risk of clinical disease progression. This observation has important implications for treatment policy and the design of future clinical trials.     

Alcohol Consumption and HIV Disease Progression: Are They Related?

BACKGROUND: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.     

Linear array genotyping and hybrid capture II assay in detecting human papillomavirus genotypes in women referred for colposcopy due to abnormal Papanicolaou smear

The main objective of this study was to assess the feasibility of human papillomavirus (HPV) genotyping in women referred for colposcopy due to abnormal Papanicolaou (Pap) smear. A series of 248 women referred for colposcopy due to an abnormal Pap smear were analysed with the Roche Linear Array HPV genotyping test detecting 37 most frequent HPV types, and compared with hybrid capture II (HCII) assay for oncogenic (high-risk [HR] HPV) types as well as for p16INK4a expression using immunocytochemistry. All tests were performed in cervical samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep), and colposcopic biopsy and/or loop electro excision procedure cone biopsy was used as the gold standard. HPV16 was the single most frequent genotype (29/258; 11.7%), followed by HPV51 (4.4%), HPV66 (3.6%), HPV42, 52 and 56 (3.2% for all). Linear array genotyping test significantly predicts both abnormal colposcopy (odds ratio [OR] = 9.0; 3.12-25.93), high-grade squamous intraepithelial lesions (OR = 9.6; 1.26-74.17) and cervical intraepithelial neoplasia (CIN) 3+ (OR = 29.3; 3.95-218.06). In detecting CIN3, linear array was equivalent (97.6%) to colposcopy in sensitivity (SE), both being superior to HCII (92.7%). Concordance between linear array and HCII was moderate (Cohen's kappa kappa = 0.547; 95% confidence interval [CI]: 0.435-659). Specificity (SP) and positive predictive value (PPV) of linear array were significantly improved, if only HPV16 genotype was considered. Performance in the best balance is obtained, when linear array and colposcopy are combined, giving 82.9% SE, 93.9% SP, 73.9% PPV and 96.3% negative predictive value (NPV) as predictor of CIN3+ (OR 74.5; 95% CI: 27.36-202.72). In conclusion, linear array for HR-HPV is a highly sensitive test (97.6%) with high NPV (98.9%) in detecting CIN3+ lesions. HPV16 genotyping alone significantly improves SP and PPV of this test in management of women with abnormal cytology.