A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993).

One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. Twenty-six patients had received prior adjuvant chemotherapy (including an anthracycline in 10). Sixteen had received non-anthracycline-based first-line chemotherapy for advanced disease. One hundred and eleven patients were evaluable for toxicity and 106 for response. The delivered dose intensity (DI) was 9.8 mg/m2 (95% CI, 7.2-10.4) with 37 (69%) achieving a DI of >90% on ARM A and 11.9 mg/m2 (95% CI, 7.5-12.8) with 37 (65%) achieving a DI of >90% on ARM B. The adverse event profiles of the two schedules were distinctly different. Mucositis was more common with the every 6 weeks regimen (35% CTC grade 3/4 in ARM A, 14% in ARM B) but palmar plantar erythrodysesthesia (PPE) was more frequent with the every 4 weeks regimen (2% CTC grade 3/4 in ARM A, 16% in ARM B). Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.

An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.

Regional differences in HIV testing among European patients with sexually transmitted diseases: trends in the history of HIV testing and knowledge of current serostatus.

OBJECTIVES: To determine trends in (1) HIV testing and knowledge of current serostatus and (2) clinic-visits of aware HIV-infected patients and (3) to determine associates of incident HIV infection among patients with sexually transmitted disease (STD) in 15 countries participating in a European Community anonymous HIV seroprevalence survey. METHODS: Demographics, STD diagnosis, self-reported history of HIV tests and current HIV test results were collected for patients diagnosed with one of 12 pre-selected STDs. Incident HIV infections were determined among patients who reported prior HIV-negative test results. RESULTS: Between June 1990 and December 1996, 66560 STD patients were tested for HIV. Of these, 1581 (2.4%) reported a prior HIV-positive test. Of 41727 (62%) patients who reported no previous HIV test, 611 (1.4%) were HIV infected. Of 20785 (31%) patients who reported a prior HIV-negative test, 213 (1.0%) were HIV infected. Of 2467 (4%) patients without prior HIV test data available 123 (4.9%) were HIV infected. Overall, 63% of HIV-seropositive patients was aware of their HIV infection. Over time, the proportion of aware HIV-seropositive patients increased in some exposure categories in south and central Europe. Among the 11684 patients who reported dates of prior HIV-negative tests, 108 HIV infections were found. Compared with the north, HIV incidence was higher in the central region [odds ratio (OR), 1.23; 95% confidence interval (CI), 0.71-2.12] and in the south (OR, 4,39; 95% CI, 2.80-6.88) in all exposure categories except homosexual men. CONCLUSIONS: Two-thirds of patients with an STD had never been tested for HIV. Of all HIV infections found, 32% were undiagnosed, indicating missed opportunities for counselling, safe sex education and referral for treatment. HIV testing should be routinely offered to all STD patients.

Effect of HIV-1 infection on tuberculosis and fertility in a large workforce in Kinshasa, Democratic Republic of the Congo.

To determine the effect of an HIV counseling service on the incidence of HIV and tuberculosis infection and on the fertility rate in a large workforce cohort of adult men and women from Kinshasa, Democratic Republic of Congo (formerly Zaire), we conducted a 2-year prospective longitudinal cohort study, two large Kinshasa businesses (a commercial bank and a textile factory). We determined baseline HIV-1 seroprevalence, HIV-1 and tuberculosis mortality/morbidity, and fertility rates during 24 months of follow-up on 8866 employees and 6411 wives of male employees. The baseline HIV-1 seroprevalence was 2.8% in male employees (n = 6657), 8.4% in female employees (n = 417), and 2.4% in the wives of male employees (n = 4692). The HIV-1 seroincidence per 100 person-years of follow-up in these three groups was 0.9, 0.5 and 0.8, respectively. The incidence of tuberculosis was 2.4/100 person years in persistently seropositive individuals compared with a 0.38 rate in persistently seronegative individuals (p < 0.01). The annual fertility rate in persistently seronegative women was 250.0/1000 women compared with a rate of 140/1000 in persistently seropositive women (p < 0.001). Forty-eight (44%) of 105 male employees and 17 (26%) of 60 wives of male workers who died during follow-up were HIV-1 seropositive. HIV infection was responsible for nearly one half of all deaths in this large workforce. Tuberculosis incidence was six times higher in HIV-1-infected compared with uninfected individuals. Counseling of HIV-infected women and their husbands appeared to be effective as their cumulative fertility rate was 44% lower than the rate in similarly aged uninfected women.

Trends in HIV seroprevalence among patients with sexually transmitted diseases in 17 European sentinel networks, 1990-1996. European Study Group.

OBJECTIVE: To monitor trends in HIV seroprevalence among sentinel populations of patients with new sexually transmitted disease episodes in 17 networks of 15 European countries. METHODS: Time trends were estimated by logistic regression for homo-/bisexual men, injecting drug users (IDU) and non-IDU heterosexuals. The networks were included as independent variables to account for different prevalence levels across Europe. Socio-demographic and behavioural data were also included in the model. The interactions of time and each factor in the model were evaluated to determine whether trends differed across networks or population subgroups. RESULTS: Overall, more than 150,000 sexually transmitted disease episodes were registered in this study. In the European network as a whole, the prevalence decreased significantly among IDU [n = 2619; odds ratio (OR) for annual change, 0.86; 95% confidence interval (CI), 0.80-0.93]. It also decreased among homo-/bisexual men (n = 11,809; OR, 0.92; 95% CI, 0.89-0.94). In both groups, trends did not differ statistically between networks. Among non-IDU heterosexuals (n = 114,024) the prevalence increased significantly (OR, 1.08; 95% CI, 1.04-1.13), especially among women (OR, 1.13) and the time trends differed statistically across networks. A significant increase was observed in four networks, whereas no specific change was detected in the others. CONCLUSIONS: By applying a standardized protocol, trends in HIV prevalence could be compared across networks and estimated at a more global level. For the validity of HIV trends in such surveys, it is essential to minimize the number of patients not being tested in networks where voluntary testing is required.

The Swiss Network of Dermatology Policlinics HIV prevalence study: rationale, characteristics and results (1990-1996).

The Swiss Network of Dermatology Policlinics (SNDP) has monitored the prevalence of HIV among patients treated for a sexually transmitted disease (STD) since January 1990. A questionnaire was sent to each policlinic in the network (Basel, Bern, Geneva, Lausanne, and two in Zurich) to collect information on their participation in this study and the characteristics of the network. The responses reveal that the six policlinics followed the HIV prevalence study protocol in a uniform manner and had similar logistical and organisational characteristics HIV prevalences in this population were high (1.6% among heterosexuals, 24.0% among male homo/bisexuals, and 35.7% among injecting drug users), have remained stable, and vary considerably by policlinic. In conclusion, we found that the policlinics have correctly implemented the HIV prevalence study and that the SNDP is a homogeneous sentinel surveillance system. Knowledge of the organisation and characteristics of the SNDP has allowed us to better interpret and present our data, and we recommend that other sentinel surveillance systems of this type collect this sort of information.

The HIV epidemic associated with injecting drug use in Europe: geographic and time trends.

OBJECTIVES: To evaluate the magnitude and trends of the HIV epidemic associated with injecting drug use in Europe. METHODS: AIDS cases associated with injecting drug users (IDU) diagnosed through 1995 were analysed, including IDU, homo-/bisexual IDU, heterosexual partners of IDU and children whose mothers were IDU. HIV seroprevalence studies among IDU were reviewed. RESULTS: Of the 171,932 cumulative AIDS cases, 73,119 (43%) were IDU-associated (IDU, 89.0%; homo-/bisexual IDU, 3.5%: heterosexual partners of IDU, 6.2%; children with IDU mothers, 1.4%). Over 90% of IDU-associated cases were concentrated in south-western European countries with considerably higher rates in Spain (124 cases per million in 1995) than elsewhere (Italy, 68 per million; Portugal, 42 per million; France, 38 per million). During 1990-1995, incidence increased at an average annual rate of 11% overall and > 23% in central and eastern Europe; overall, incidence increased in older persons (12%) while decreasing in those aged 13-24 years (by 6%). HIV prevalence in IDU showed considerable geographic variation across and within countries. In several countries of western Europe, prevalence decreased. In the former Soviet Union, large HIV outbreaks have recently been detected among IDU through systematic HIV testing (e.g., in Ukraine, 6750 HIV infections were diagnosed in IDU tested during 1995-1996). CONCLUSIONS: IDU have played a major role in the spread of HIV in Europe. In several western European countries, the incidence of HIV acquired through drug use has declined following high rates in mid-1980s. Studies to assess current transmission are needed and prevention efforts must be maintained. In eastern Europe, emerging epidemics reinforce the urgency for prevention.

HIV status of female sex partners of men reactive to HIV-1, HIV-2 or both viruses in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare rates of serologic concordance in the female sex partners of men with HIV-1 and HIV-2 infections, and to determine the serologic status of sex partners of men who reacted serologically to both viruses. DESIGN: Cross-sectional study. SETTING: Infectious diseases service in a University Hospital in Abidjan, Côte d'Ivoire (West Africa). PARTICIPANTS: Hospitalized men reactive on synthetic peptide-based tests to HIV-1, HIV-2 or both viruses (dually reactive), and their spouses visiting them in hospital. OUTCOME MEASURES: Serologic status of female spouses of seropositive men. RESULTS: The serologic status of 540 spouses of 490 HIV-1- and/or HIV-2-positive, hospitalized men was studied. Similar proportions of spouses of HIV-1-infected men (49%) and HIV-2-infected men (44%) were concordantly seropositive. The overall prevalence of infection in spouses of dually reactive men (72%) was significantly higher than in spouses of other men; 44% of these spouses were infected with HIV-1, 8% with HIV-2, and 20% were themselves dually reactive. Considering only the seropositive female spouses of men monotypically reactive to HIV-1 or HIV-2, and the male spouses of women monotypically infected, rates of serologic discordance were significantly greater in men (24%) than women (7%). CONCLUSIONS: Men were likely to have been infected earlier than women because of their HIV-associated illness; also, men more frequently had serologic profiles indicative of infection outside of the union. Rates of serologic concordance in spouses of men with advanced HIV-1 or HIV-2 infection were similar (44-49%). Dually reactive hospitalized men frequently (72%) had seropositive sex partners, most of whom were HIV-1-positive. Dual reactivity was also frequent in these spouses, suggesting transmission of both HIV-1 and HIV-2, or of a cross-reactive strain, and a minority of partners were infected with HIV-2 alone. Prospective studies of discordant couples using quantitative molecular diagnostic techniques are required for better understanding of dual reactivity and transmission of HIV-1 and HIV-2.

High HIV-1 incidence in young women masked by stable overall seroprevalence among childbearing women in Kinshasa, Zaïre: estimating incidence from serial seroprevalence data.

OBJECTIVE: To describe the dynamics of the HIV-1 epidemic in childbearing women in Kinshasa, Zaïre, by estimating incidence from serial seroprevalence studies. METHODS: In 1986 and 1989, 5937 and 4623 pregnant women, respectively, were screened for HIV-1 in Kinshasa. We estimated age-specific incidence from two seroprevalence surveys by using a birth-year cohort analysis and adjusting for differences in mortality and fertility between HIV-1-infected and uninfected women. Mortality and fertility data were measured in a cohort of women recruited from the survey in 1986 and followed until 1989. RESULTS: While the overall HIV-1 seroprevalence changed little (5.8% in 1986 and 6.5% in 1989; P = 0.17), the prevalence increased in birth-year cohorts of women under 25 years of age in 1989 from 3.2 to 6.2% (P < 0.001), but decreased for women above 25 years of age from 6.9 to 6.7% (P = 0.7). In addition, new HIV infections between 1986 and 1989 were balanced by a higher mortality and lower fertility observed in HIV-infected women. After adjusting for these effects, we estimated an overall 3-year cumulative HIV-1 incidence of 2.8 per 100 uninfected women [95% confidence interval (CI), 1.4-4.2]. The highest incidence, 5.7 per 100 (95% CI, 3.5-8.0), was in women aged 20-24 years in 1989. CONCLUSION: Despite an overall relatively stable HIV-1 prevalence in childbearing women in Kinshasa between 1986 and 1989, approximately 40% of all HIV-1 infections detected in the 1989 survey occurred between 1986 and 1989, and 60% occurred in women under 25 years of age in 1989.

AIDS orphans in Kinshasa, Zaïre: incidence and socioeconomic consequences.

OBJECTIVE: To determine the incidence, morbidity, mortality, and socioeconomic consequences of becoming an AIDS orphan (a child with an HIV-1-seropositive mother who has died) in Kinshasa, Zaïre. DESIGN: A longitudinal cohort study was undertaken between 1986 and 1990. Within this cohort, a nested case-control study of AIDS orphans was performed. AIDS orphan cases were children with an HIV-1-seropositive mother who had died. Two groups of control children were identified. The first group of control children were age-matched children with HIV-1-seropositive mothers who were alive at the time of death of the AIDS orphan case mother. The second group of control children were children with HIV-1-seronegative mothers who were also alive at the time of death of the AIDS orphan case mother. SETTING: Obstetric ward and follow-up clinic at two large municipal hospitals in Kinshasa, Zaïre. PARTICIPANTS: A total of 466 HIV-1-seropositive women, their children, and the fathers of these children; 606 HIV-1-seronegative women, their children, and the fathers of these children. MAIN OUTCOME MEASURES: AIDS orphan incidence, HIV-1 vertical transmission rate, morbidity, mortality and socioeconomic indicators of the consequences of becoming an AIDS orphan. RESULTS: The AIDS orphan incidence rate was 8.2 per 100 HIV-1-seropositive women-years of follow-up. Vertical transmission of HIV-1 was higher in AIDS orphan cases (41%) than in control children with HIV-1-seropositive mothers (26%; P < 0.05). Among children without vertically acquired HIV-1 infection, morbidity rates and indices of social and economic well-being were similar in AIDS orphans and control children. Five out of 26 (19%) AIDS orphan cases died during follow-up, compared with three out of 52 (6%) control children (P < 0.05). CONCLUSION: During a 3-year follow-up period, children with HIV-1-seropositive mothers had a considerable risk of becoming an AIDS orphan. However, the presence of a concerned extended family appeared to minimize any adverse health and socioeconomic effects experienced by orphan children.

Retrospective study of maternal HIV-1 and HIV-2 infections and child survival in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the effects of maternal HIV-1 and HIV-2 infections on outcome of pregnancy, infant mortality, and child survival, and to measure serological concordance between mothers and children. DESIGN: Retrospective cohort study with cross sectional study of concordance for HIV antibodies. SETTING: Hospital, tuberculosis clinic, and maternal and child health centre in Abidjan, Côte d'Ivoire, west Africa. SUBJECTS: 986 women who had had a total of 2758 pregnancies since 1980. The last born children of 194 of these women. MAIN OUTCOME MEASURES: Pregnancy outcomes; mortality for all children born since 1980; and outcome for last born children. Serological concordance between mothers and last born children. RESULTS: Women with HIV-1 and HIV-2 infections had higher rates of spontaneous abortion and stillbirth than uninfected women (86/769 in HIV-1 positive women, 48/421 in HIV-2 positive, 31/234 in dually reactive, and 96/1131 in uninfected). Compared with children born to uninfected mothers (mortality 10.3%), greater proportions of children of HIV-1 positive (20.6%) and dually reactive (20.3%) mothers had died; mortality in children of HIV-2 infected women (13.1%) was not significantly increased. Infant mortalities for the last born children of HIV-1 positive, dually reactive, HIV-2 positive, and seronegative women were, respectively, 133, 82, 32, and 40 per 1000 live births. Nine of 77 last born children of HIV-1 positive mothers were concordantly seropositive compared with none of 21 children of HIV-2 infected mothers. CONCLUSIONS: Maternal HIV-2 infection has less influence on child survival than infection with HIV-1, probably because of a lower vertical transmission rate.

Excluding blood donors at high risk of HIV infection in a west African city.

OBJECTIVE: To examine the potential impact of deferral of blood donors at high risk of HIV infection in a west African city where blood is screened for HIV antibodies but no other special measures are taken to protect the blood supply. DESIGN: Cross sectional study. SETTING: National Blood Transfusion Centre and Project RETRO-CI, an international collaborative AIDS research project, Abidjan, Côte d'Ivoire. SUBJECTS: 1257 male first time blood donors. INTERVENTIONS: Blood donors were interviewed about demographic and behavioural characteristics and tested for HIV antibodies by enzyme immunoassay and, if positive, synthetic peptide based tests. MAIN OUTCOME MEASURES: HIV antibody status in relation to presence of behavioural risk factors; calculation of sensitivity, specificity, and predictive values of specific criteria for excluding HIV infected donors. RESULTS: The overall prevalence of HIV infection was 11.4%. The most important risk factors for HIV positivity were prostitute contact and being aged 30-39 years. For identifying seropositive donors individual criteria had sensitivity, specificity, and positive predictive values ranging from 15% to 98%, 38% to 91%, and 17% to 30% respectively. Prostitute contact in the past five years would have excluded 31% of all donors and 73% of HIV infected donors. 27% of those excluded would have been HIV positive. CONCLUSIONS: The widespread assumption that donor deferral is not feasible in sub-Saharan Africa needs reassessment. In Abidjan this approach was well accepted and potentially effective. Donor deferral requires evaluation as a strategy for improving blood safety in resource poor areas with high rates of HIV infection.

PIP: During February-November 1991 in Abidjan, the Ivory Coast, interviews with 1257 male first-time blood donors and screening of their blood for antibodies to HIV-1 and HIV-2 were conducted at the National Blood Transfusion Center to determine whether it is feasible to exclude or defer donors at high risk of HIV infection. 143 (11.4%) men had antibodies to HIV. The multivariate analysis showed that the strongest risk factor for HIV infection was sex with prostitutes in the last 5 years without regular condom use (odds ratio [OR] = 10, confidence interval [CI] = 6.6-15) followed by prostitute contact in the last 5 years regardless of condom use (OR = 8.4, CI = 5.6-12.6), and an age of 30-39 years (OR = 6.9, CI = 18). 27% of all donors with prostitute contact in the last 5 years were infected (positive predictive value). If the center had used prostitute contact in the last 5 years as a criterion, it would have discarded 31% of all units of blood. Thus, more than 75% of all potentially excluded units would have been from donors infected with HIV. The sensitivity, specificity, and positive predictive values ranged from 15% to 98%, 38% to 91%, and 17% to 30%, respectively. These findings suggest that it is feasible in Abidjan to exclude donors based on behavioral characteristics of those most at risk of HIV infection. Donor deferral should be evaluated as a strategy to improve blood safety in resource-poor areas with high rates of HIV infection.

Impact of HIV counseling and testing among child-bearing women in Kinshasa, Zaïre.

OBJECTIVE: To determine the impact of HIV counseling and testing among child-bearing women. STUDY SETTING: Mama Yemo Hospital in Kinshasa, Zaïre. PARTICIPANTS AND INTERVENTIONS: After informed consent, 187 HIV-seropositive and 177 HIV-seronegative child-bearing women received pre- and post-test counseling for HIV infection. MAIN OUTCOME MEASURES: Participant knowledge of HIV/AIDS and plans for notifying partners of serologic status and contraceptive use at the time of counseling, and actual partner involvement and contraception use 12 months later. RESULTS: During pre-test counseling, participant knowledge of HIV infection was high, although 30% of women were unaware of perinatal HIV transmission, and 50% did not know that HIV infection could be asymptomatic. At post-test counseling, 70% of mothers (47% of HIV-seropositive, 94% of HIV-seronegative) intended to notify their partners and have joint counseling and testing, although after 12 months, only 2.2% of all women and 7.9% of those who desired assistance to notify their partner returned with their partners for joint counseling and testing. Similarly, 86% planned to use birth control (61% condoms), with HIV-seropositive women more likely to prefer condoms than HIV-seronegative women (71 versus 53%; P < 0.001). After 12-months, however, only 20% of HIV-seropositive women reported condom use, and the frequency of pregnancy in both groups was approximately equal. CONCLUSIONS: HIV counseling and testing led to higher rates of contraceptive and condom use, although the actual level was lower than the intended use. To further reduce the risk of heterosexual and perinatal HIV transmission in families with an HIV-infected woman, counseling should also include their male partners.

Risk for perinatal HIV-1 transmission according to maternal immunologic, virologic, and placental factors.

OBJECTIVE: To evaluate how maternal and obstetric factors interact to influence mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission. DESIGN: Prospective, observational cohort study of children born to HIV-infected women to determine child's HIV infection status. The analysis then compared peripartum maternal, placental, and obstetric variables between HIV-1 transmitter and nontransmitter women. SETTING: Two large maternity wards in Kinshasa, Zaire. PARTICIPANTS: Consecutive sample of 324 HIV-1-infected women at delivery, with 254 HIV-seronegative women followed up as control subjects. PRINCIPAL OUTCOME MEASURES: HIV infection status of children, to classify each woman as an HIV-1 transmitter or nontransmitter. RESULTS: The highest transmission risk (TR) was associated with maternal p24 antigenemia (TR, 71%; relative risk [RR], 3.0; 95% confidence interval [CI], 1.7 to 5.2) and maternal CD8+ lymphocyte counts of at least 1.80 x 10(9)/L (1800/microL) (TR, 50%; RR, 2.2; 95% CI, 1.2 to 4.2). Among women with CD8+ lymphocyte counts of less than 1.80 x 10(9)/L, CD4+ lymphocyte counts of less than 0.60 x 10(9)/L were a risk factor (TR, 29%; RR, 2.2; 95% CI, 1.2 to 4.2). In women with neither high CD8+ nor low CD4+ lymphocyte counts, placental membrane inflammation was associated with perinatal transmission (TR, 40%; RR, 4.2; 95% CI, 1.3 to 13.7). In women with neither p24 antigenemia, high CD8+ or low CD4+ lymphocyte counts, nor placental membrane inflammation, the transmission risk was only 7%. Additional correlates of transmission included maternal anemia and fever, but not maternal sexually transmitted diseases. CONCLUSIONS: Identifiable subgroups of HIV-1-infected women based on maternal and placental characteristics had between a 7% and 71% risk of perinatal HIV-1 transmission. Not only the overall rate of transmission but the impact of different risk factors for transmission appear to vary over the course of HIV infection.

Safety and immunogenicity of bacille Calmette-Guérin, diphtheria-tetanus-pertussis, and oral polio vaccines in newborn children in Zaire infected with human immunodeficiency virus type 1.

OBJECTIVE: To determine the safety and immunogenicity of childhood vaccines in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection. DESIGN: Nonrandomized, prospective cohort study; 12-month follow-up period. SETTING: Obstetric wards and outpatient pediatric clinics at two large hospitals in Kinshasa, Zaire. PATIENTS: A total of 8108 pregnant women were screened for HIV-1 antibodies. The 474 children born to 466 seropositive women identified during screening and the 616 children born to 606 seronegative, age- and parity-matched women were vaccinated. INTERVENTION: The following vaccines were administered at the stated ages: bacille Calmette-Guérin (BCG) vaccine (2 days); trivalent oral Sabin poliomyelitis vaccine (2 days and 6, 10, and 14 weeks); and adsorbed diphtheria-tetanus-pertussis (DTP) vaccine (6, 10, and 14 weeks). MEASUREMENTS AND MAIN RESULTS: Protective antibody titers to tetanus and poliovirus types 1, 2, and 3 were achieved in 95% of all children. Among children with HIV-1 infection, 70.8% had protective antibody titers to diphtheria compared with 98.5% of uninfected children (p < 0.05). Geometric mean antibody titers to diphtheria and poliovirus types 1, 2, and 3 were significantly lower in children with HIV-1 infection than in uninfected children. Vaccine-associated side effects were similarly low in all children. CONCLUSIONS: The low incidence of side effects and the high proportion of children with HIV-1 infection who achieved protective postimmunization antibody titers support the continuing use of BCG, DTP, and oral polio vaccines in childhood immunization programs in HIV-1 endemic areas.

Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study.

OBJECTIVES: The heterosexual spread of HIV-1 is occurring at different rates in different parts of the world. The transmission probability of HIV-1 per sexual contact is low, but may be greatly enhanced by several cofactors. Sexually transmitted diseases (STD), especially genital ulcers, may be such factors. So far, epidemiological evidence that other STD facilitate HIV-1 transmission is weak. The objective of this study was to determine whether treatable STD enhanced sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. METHODS: We conducted a nested case-control study of 431 initially HIV-1-negative women followed prospectively for a mean duration of 2 years (with monthly STD check-ups and 3-monthly HIV-1 serology). Cases (seroconverters, n = 68) were compared with controls (women who remained HIV-1-negative, n = 126) for incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. RESULTS: The annual incidence of HIV-1 in this cohort was 9.8%. Seroconverters were younger than HIV-1-negative women (mean age, 24.6 versus 26.8 years; P = 0.04). During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhoea, chlamydial infection and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratios for seroconversion were 4.8 [95% confidence interval (CI), 2.4-9.8] for gonorrhoea, 3.6 (95% CI, 1.4-9.1) for chlamydial infection and 1.9 (95% CI, 0.9-4.1) for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. CONCLUSION: Non-ulcerative STD were risk factors for sexual transmission of HIV-1 in women, after controlling for sexual exposure. Because of their high prevalence in some populations, non-ulcerative STD may represent a considerable population-attributable risk in the transmission of HIV-1 worldwide. The identification of treatable STD as risk factors for HIV-1 transmission offers an important additional strategy for the prevention of HIV/AIDS.

PIP: There is only a small probability that HIV-1 will be transmitted via any single sexual contact. The risk of transmission, however, during such an act may be greatly increased by the presence of ulcerative genital sexually transmitted disease (STD). Little evidence is published on whether infection with non-ulcerative STD facilitates the transmission of HIV-1. The authors therefore investigated whether treatable STD enhanced the sexual transmission of HIV-1 in a cohort of female prostitutes in Kinshasa, Zaire. 431 initially HIV-1-seronegative women were followed prospectively in this nested case-control study for a mean duration of two years in monthly STD check-ups and three-monthly HIV-1 serology. The 68 women who seroconverted were compared against the 126 women who remained HIV-1-seronegative for the incidence of STD and sexual exposure during the presumed period of HIV-1 acquisition. There was a 9.8% annual incidence of HIV-1 in this cohort of subjects. Seroconverters were of mean age 24.6 years compared to 26.8 years for the HIV-seronegative women. During the period of HIV-1 acquisition, cases had a much higher incidence of gonorrhea, chlamydial infection, and trichomoniasis, and engaged in unprotected sex with clients and partners more frequently than controls. After controlling for sexual exposure by multivariate analysis, adjusted odds ratio for seroconversion were 4.8 for gonorrhea, 3.6 for chlamydial infection, and 1.9 for trichomoniasis. Genital ulcers were more frequent in cases than controls, but much less common than other STD. These findings therefore suggest that non-ulcerative STDs were risk factors for the sexual transmission of HIV-1 in these women. Such STD may be a considerable population-attributable risk in the transmission of HIV-1 worldwide given the high prevalence of non-ulcerative STDs in some populations.

Stability of human immunodeficiency virus type 1 antibodies in whole blood dried on filter paper and stored under various tropical conditions in Kinshasa, Zaire.

The use of whole-blood spots on filter paper for the detection of antibody to human immunodeficiency virus type 1 (HIV-1) was evaluated during a 20-week period under a variety of storage environments simulating the harsh tropical field conditions in Kinshasa, Zaire. During the first 6 weeks of storage, all replicates of high- and low-titer HIV-1-positive reference samples remained positive by enzyme immunoassay and Western blotting (immunoblotting), and all replicates of HIV-1-negative samples remained negative under all storage conditions. However, hot and humid storage conditions for up to 20 weeks caused a progressive decline in enzyme immunoassay optical density ratio values, which was particularly noticeable in samples with a low HIV-1 antibody titer. Harsh tropical operational conditions did not cause any repeatedly false-positive results during the 20-week storage period. The use of gas-impermeable bags with desiccant for the storage of blood spots on filter paper improved the stability of HIV-1 antibody detection over time and is recommended for the storage of whole-blood spots on filter paper in harsh tropical field settings.

Fertility rates in 238 HIV-1-seropositive women in Zaire followed for 3 years post-partum.

Birth-control use and fertility rates were prospectively determined in 238 HIV-1-seropositive and 315 HIV-1-seronegative women in Kinshasa, Zaire, during the 36-month period following the delivery of their last live-born child. No women delivered children during the first follow-up year. Birth-control utilization rates (percentage use during total observation time) and fertility rates (annual number of live births per 1000 women of child-bearing age) in the second year of follow-up were 19% (107.4 per 1000) for HIV-1-seropositive women and 16% (144.7 per 1000) for HIV-1-seronegative women. In the third year of follow-up these rates were 26 (271.0 per 1000) and 16% (38.6 per 1000) for HIV-1-seropositive and HIV-1-seronegative women, respectively (P less than 0.05 for the difference in birth-control utilization and fertility rates between seropositive and seronegative women in the third year of follow-up). Seven (2.9%) of the 238 HIV-1-seropositive women initially included in the study brought their sex partners in for HIV-1 testing; three (43%) of these men were found to be HIV-1-seropositive. New HIV-1 infection did not have a dramatic effect on the fertility of seropositive women. The nearly uniform unwillingness of HIV-1-seropositive women to inform husbands or sexual partners of their HIV-1 serostatus accounted in large part for the disappointingly high fertility rates in seropositive women who had been provided with a comprehensive program of HIV counseling and birth control. Counseling services for seropositive women of child-bearing age which do not also include these women's sexual partners are unlikely to have an important impact on their high fertility rates.

Evidence from Zaire that breast-feeding by HIV-1-seropositive mothers is not a major route for perinatal HIV-1 transmission but does decrease morbidity.

Breast-feeding as a route of HIV-1 transmission during infancy but also as a protective measure against early childhood morbidity has been investigated prospectively in children born to HIV-1-seropositive mothers and control children born to age- and parity-matched HIV-1-seronegative women. The mothers of all study children had been enrolled antenatally at a maternity hospital in Kinshasa, Zaire, which served a relatively affluent group of women who sometimes chose not to breast-feed their infants. In 106 children born to HIV-1-seropositive women, the rate of HIV-1 transmission was 21% in 28 infants exclusively breast-fed, 19% in 68 infants both breast- and bottle-fed and 0% in 10 infants who were bottle-fed only (P = 0.35). In contrast, non-HIV-1-infected children of both HIV-1-seropositive and HIV-1-seronegative mothers who were exclusively breast-fed compared with uninfected children who were not exclusively breast-fed had significantly lower incidence rates of acute diarrhea, fever and lower respiratory tract infection. The lack of a dose-response effect between breast-feeding and perinatal HIV-1 transmission and the presence of a protective effect of breast-feeding against common causes of early childhood morbidity and mortality support the current World Health Organization recommendation that breast-feeding should continue to be promoted in all developing countries, including those with high HIV-1 prevalence rates in women of childbearing age.