Pregnancies before and after HIV diagnosis in a european cohort of HIV-infected women. European Study on the Natural History of HIV Infection in Women.

OBJECTIVES: Because most HIV-infected women are of reproductive age, we investigated whether their reproduction planning was affected by their HIV diagnosis. DESIGN: The European women study is a prospective, multicentre cohort of 485 HIV-infected women with a known interval of seroconversion. METHODS: The incidence of pregnancy was measured with person-time methods. Generalized estimating equation analysis was used to determine risk factors for pregnancy and pregnancy outcomes. RESULTS: In 449 women, the age-adjusted incidence of pregnancies decreased from 8.6 before HIV diagnosis to 8.2 and 6.0 per 100 person-years in 0-4 and over 4 years after HIV diagnosis, respectively (P = 0.14). The proportion of induced abortions increased from 42% before to 53% after HIV diagnosis (P < 0.05). The risk of spontaneous abortion did not increase as a result of HIV infection. Since 1995, the proportion of births increased (P = 0.009), whereas that of induced abortions decreased (P = 0.01) compared with earlier years. An increased risk of pregnancy after HIV diagnosis was found in northern and central European women compared with southern European women; there was a lower risk in single women than in women with a steady partner. Of all pregnant women, single women, women between 15 and 25 years of age, and women with multiple partners were at increased risk for induced abortion both before and after HIV diagnosis. CONCLUSION: The incidence of pregnancy decreased with HIV disease progression. Pregnancies after HIV diagnosis appear to be related largely to social and cultural attitudes. The number of induced abortions was high before HIV diagnosis and it significantly increases thereafter.

Prevention of mother-to-child HIV transmission in resource-poor countries: translating research into policy and practice.

Each year, an estimated 590,000 infants acquire human immunodeficiency virus type 1 (HIV) infection from their mothers, mostly in developing countries that are unable to implement interventions now standard in the industrialized world. In resource-poor settings, the HIV pandemic has eroded hard-won gains in infant and child survival. Recent clinical trial results from international settings suggest that short-course antiretroviral regimens could significantly reduce perinatal HIV transmission worldwide if research findings could be translated into practice. This article reviews current knowledge of mother-to-child HIV transmission in developing countries, summarizes key findings from the trials, outlines future research requirements, and describes public health challenges of implementing perinatal HIV prevention interventions in resource-poor settings. Public health efforts must also emphasize primary prevention strategies to reduce incident HIV infections among adolescents and women of childbearing age. Successful implementation of available perinatal HIV interventions could substantially improve global child survival.

Comparative prevalence, incidence and short-term prognosis of cervical squamous intraepithelial lesions amongst HIV-positive and HIV-negative women.

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.

Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV.

Although individuals infected with human immunodeficiency virus (HIV) seem to be more infectious in the late stages of HIV infection and possibly also during the seroconversion period, most estimates of per-sexual-contact infectivity have been obtained without allowing for variability over the course of infection. In this analysis, a probabilistic model was fitted to data from a European study carried out between 1987 and 1992 that involved 499 (359 males and 140 females) HIV-infected subjects (index cases) and their regular heterosexual partners. The model used allowed infectivity (the per-sexual-contact HIV transmission probability, mu) to vary through three stages: the first 3 months following infection, the subsequent asymptomatic period, and the advanced stage (HIV-related clinical symptoms or a CD4-positive T lymphocyte count less than 200/mm3). Male-to-female infectivity through penile-anal sex was found to be higher in both the early and advanced stages of infection (mu=0.183) than in the longer intermediate period (mu=0.014) (p < 0.03). Failure to demonstrate significant differences between stages for other types of contact (male-to-female penile-vaginal contacts: mu=0.0007; female-to-male transmission: mu=0.0005) may reflect insufficient power rather than a true lack of variability. Indeed, the results for penile-anal sex suggest that persons who are in the process of seroconverting may be much more infectious than asymptomatic infected persons, whatever the type of contact. Prevention education should stress the risk of HIV transmission from subjects who may be unaware of their infection.

Acceptability of voluntary HIV testing by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To evaluate acceptability of voluntary HIV counselling and testing (VCT) by pregnant women in the context of clinical trials assessing interventions to reduce mother-to-child transmission (MCT) of HIV in developing countries. METHODS: During September-October 1997, 13 studies located in West (Abidjan, Bobo Dioulasso), East (Nairobi, Mombasa, Dar Es Salaam, Blantyre, Lusaka, Harare) and South Africa (Soweto, Durban), and Thailand (Bangkok) were included in a cross-sectional mailing survey about the acceptability of VCT in antenatal clinics. Acceptance rate, return rate, overall acceptability of VCT (acceptance of both pre- and post-VCT sessions) were obtained using a standardized questionnaire. RESULTS: The median overall acceptability of VCT was 69% (range, 33-95%). Overall acceptability of VCT most frequently depended on return rates because acceptance rates were generally high. Where several studies were conducted in parallel in the same city or the same country, overall acceptability rates of HIV testing were generally comparable even if the intervention programmes differed. Overall acceptability rates of VCT were high in antenatal clinics where a particular effort in implementing VCT programmes had been made. CONCLUSIONS: This international survey shows that despite many obstacles, VCT is feasible and acceptable for pregnant women aiming to reduce their risk of transmitting HIV to their children.

HIV-1 detection in cervicovaginal secretions during pregnancy.

OBJECTIVE: To assess the reproducibility of and factors associated with HIV detection in cervicovaginal secretions (CVS). DESIGN: Longitudinal study of 43 HIV-1-infected pregnant women in Paris. METHODS: HIV DNA was detected in peripheral blood mononuclear cells (PBMC) by Amplicor and gag nested polymerase chain reaction (PCR) assays. The HIV genotype was determined by heteroduplex mobility assay. Amplicor and gag nested PCR assays were performed on serial CVS samples for HIV DNA detection, and the HIV Monitor test was used for HIV RNA detection in plasma and CVS. RESULTS: A total of 144 CVS samples were collected from the women included in the study. HIV-1 DNA was detected in 36 (25%) of the 144 samples, from 16 (37.2%) of the 43 women. Results of HIV-1 DNA detection were concordant in the first two samples in 27 (84.4%) of the 32 women with at least two CVS samples. The last CVS sample collected in each woman was HIV-1 DNA-positive in 13 (30.2%) of the 43 women. Three factors were found to be independently associated with HIV-1 DNA detection in CVS: HIV-1 subtype B, absence of zidovudine therapy, and microbial cervicovaginal infection. HIV RNA was detected in CVS from 10 (23.3%) out of 43 women and correlated with DNA detection in the same sample and HIV RNA detection in plasma. CONCLUSIONS: DNA and RNA PCR can be used to detect HIV in cells and supernatants of CVS. These techniques may be useful in cohort studies to investigate HIV transmission and to evaluate the efficacy of antiretroviral drugs to reduce HIV excretion.

Pregnancy and contraception in a French cohort of HIV-infected women. SEROCO Study Group.

OBJECTIVE: To describe the impact of HIV diagnosis on contraception, incidence of pregnancy and live-births among HIV-infected women in France. DESIGN: Follow-up of women included in a French cohort of HIV-infected adults (SEROCO). METHODS: In 17 hospital-based units and one private practitioners' network in the Paris area and south-east region of France, 412 HIV-infected women (volunteers) were enrolled from 1988 to 1993, shortly after HIV diagnosis (median, 3 months), and followed for a median of 3 years. The main outcome measures were incidence and outcome of pregnancy, proportions of women sexually active and methods of contraception. RESULTS: The incidence of pregnancy decreased significantly from 20.4 per 100 person-years in the year preceding HIV diagnosis to 7.9 per 100 person-years after HIV diagnosis (P < 0.001), whereas the proportion of pregnancies voluntarily interrupted doubled (63 versus 29%). The proportion of women who were sexually inactive increased from 5% before HIV diagnosis to 20% thereafter. During followup, 80% of sexually active women were using contraceptive methods. CONCLUSIONS: The study supports an association between the discovery of HIV infection and a decrease in the proportion of women who are sexually active, a decrease in the incidence of pregnancy in general and live-births in particular, and an increase in the proportion of pregnancies voluntarily interrupted. Nevertheless, 24% of the women became pregnant and around 20% of sexually active women were not using any contraception. The high rate of voluntary abortion may indicate that many of these pregnancies were unplanned and could have been prevented.

Probability of heterosexual transmission of HIV: relationship to the number of unprotected sexual contacts. European Study Group in Heterosexual Transmission of HIV.

The objective of this study was to investigate the relationship between the number of unprotected heterosexual contacts with an HIV-infected person and the probability of HIV transmission. Data from a European study involving 563 heterosexual partners of HIV-infected subjects were analyzed. The number of unprotected contacts could be estimated for 525 couples (377 with male index case, 148 with female index case) from the reported frequency of unprotected contacts and an estimate of the length of the period during which transmission could have occurred. Nonparametric (isotonic regression) and parametric (Bernoulli model) analyses were performed on data at study entry and on follow-up data (121 couples). The nonparametric analysis resulted in several exposure groups, with the proportion of infected partners increasing with the number of contacts. For example, the percentage of female partners infected ranged from 10%, among those with < 10 unprotected contacts with an infected male, to 23% after 2,000 unprotected contacts. The parametric estimates of (assumed constant) per-contact infectivity were higher for male-to-female than for female-to-male transmission, but not significantly so. However, in comparison with nonparametric estimates, the model assuming constant infectivity appears to seriously underestimate the risk after very few contacts and to seriously overestimate the risk associated with a large number of contacts. Our results suggest that the association between the number of unprotected sexual contacts and the probability of infection is weak and highly inconsistent with constant per-contact infectivity. Probable explanations for these findings include large variability in infectivity between couples and within individuals over time. Estimates based on partner study data under the hypothesis of constant infectivity can, therefore, be highly misleading at a public health level, particularly when extrapolated to multiple casual contacts.

A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV.

BACKGROUND: Worldwide, the predominant mode of human immunodeficiency virus (HIV) transmission is heterosexual intercourse, but the risk of heterosexual transmission and the effectiveness of measures to prevent it are not well defined. METHODS: We conducted a prospective study of HIV-negative subjects whose only risk of HIV infection was a stable heterosexual relationship with an HIV-infected partner. Every six months the subjects were interviewed, tested for HIV, and counseled about safe sexual practices. RESULTS: A total of 304 HIV-negative subjects (196 women and 108 men) were followed for an average of 20 months. During the study, 130 couples (42.8 percent) ended their sexual relationships, most often because of the HIV-infected partner's illness or death. Of the 256 couples who continued to have sexual relations for more than three months after enrollment in the study, only 124 (48.4 percent) used condoms consistently for vaginal and anal intercourse. Among these couples, none of the seronegative partners became infected with HIV, despite a total of about 15,000 episodes of intercourse. Among the 121 couples who used condoms inconsistently, the rate of seroconversion was 4.8 per 100 person-years (95 percent confidence interval, 2.5 to 8.4). Eleven couples refused to answer questions about condom use. The risk of transmission increased with advanced stages of HIV infection in the index partners (P < 0.02) and with genital infection in the HIV-negative partners (P < 0.04). Withdrawal to avoid ejaculation in the vagina had a protective effect in uninfected women (P < 0.02). CONCLUSIONS: Consistent use of condoms for heterosexual intercourse is highly effective in preventing the transmission of HIV. Among couples not using condoms regularly, the risk of HIV transmission varies widely.

Importance of the familial factor in varicose disease. Clinical study of 134 families.

BACKGROUND: The role of heredity in the development of varicose veins of the lower limbs has been raised many times in the literature. When evaluating this role, most authors only question the patients, without examining their relatives. As shown in other papers, the subjectivity of this type of data throws doubt on the results. OBJECTIVE: This problem was evaluated by means of a prospective study based on clinical examination of all immediate family members. METHODS: In the case-control study, the female or male patients had to satisfy the following criteria: 1. Varicose veins in their legs. 2. Age between 30 and 40 years (meaning that, in most cases, their parents were still alive). 3. No history of deep vein thrombosis. To limit the influence of certain confusing factors (diet, life-style), the control group was composed of the patients' spouses, who were not suffering from varicose veins. The parents of the cases and the parents of the controls were also examined. For each case-control couple and for the four parents, we recorded the history of venous disease, the life-style, and the results of clinical examination, including the results of palpation and percussion of the various varicose vein territories. RESULTS: One hundred and thirty-four families were examined: 67 patients and their parents and 67 controls and their parents. A total of 402 subjects were examined. The results demonstrated a prominent role of heredity in the development of varicose veins (P < .001). The risk of developing varicose veins for the children was 90% when both parents suffered from this disease, 25% for males and 62% for females when one parent was affected, and 20% when neither parent was affected.

Male circumcision: a role in HIV prevention?

PIP: Speculation has existed for decades on the association between the lack of male circumcision and the sexual transmission of disease. It has been suggested that the surface epithelium of the glans develops a protective keratin layer following circumcision which functions like a natural condom against contracting disease. Circumcised males may therefore be less susceptible to contracting sexually transmitted diseases (STD), including HIV. The identification of simian immunodeficiency virus-infected mononuclear cells in the dermis and epidermis of the penile foreskin of macaques also suggests that male circumcision may reduce the infectivity of men with HIV. The authors review the evidence in support of the association between the lack of circumcision and STDs, and the possible biological explanations. They also discuss the implications for public health interventions and suggest areas and methods for further research. Twenty-three published study reports linking circumcision status to HIV infection are identified and include retrospective studies including partner studies, cross-sectional serosurveys, a longitudinal study, and ecological correlations. Five studies linked the lack of circumcision to STDs other than HIV infection. In interpreting the data, the authors consider susceptibility versus infectivity, assessment of behaviors and adjustment for confounding, selection bias, misclassification of exposure, measure of association, and publication bias. It is ultimately concluded that more studies are needed to quantify the relative risk associated with the lack of male circumcision. Observational designs could be employed to that end along with laboratory and primate research.^ieng

Evaluation of different systems for clinical quantification of varicose veins.

One hundred twenty-five lower limbs with varicose veins were studied clinically, essentially by palpation. Two specialists in venous pathology scored the severity of the varicose veins from 0 to 20. Comparison between the different clinical parameters and the scores of the specialists showed that two systems of clinical quantification gave good results and were easy to use. One system is the maximum diameter of the largest varicose vein; the other system is the sum of maximum diameters over 7 sections (3 for thigh, 3 for leg, 1 for foot). This latter system gives a more precise evaluation of the clinical severity of the varicose veins.

Alcohol consumption in a case-control study of breast cancer in southern France.

The effect of alcohol consumption on breast cancer risk was investigated in a hospital-based, case-control study of 808 patients (349 cases and 459 controls) in Montpellier (France). Semi-quantified diet history including beverage consumption as well as relevant medical and personal characteristics were assessed by interview. A dose-rate relationship for total alcohol consumption was found with unadjusted odds ratios ranging from 1.8 (95% CI 1.2-2.8) for 1 to 2 drinks per week to 3.5 (95% CI 2.0-6.1) for more than 17 drinks per week, in comparison with less than 1 drink per week. Confounding by known or suspected determinants of breast cancer, smoking, use of oral contraceptives, lipid and vitamin consumption was looked into. Significant interactions were found with level of education and lipid consumption, with a higher risk for alcohol in women having had less schooling or consuming less fat. Adjustment with respect to the other risk factors did not modify the relationship. There was a significant risk increase both for wine and stronger drinks. Along with several other studies, our results give support to the hypothesis that alcohol is a risk factor in breast carcinogenesis.