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Frerichs, R.R. Heterosexual HIV transmission and testing.

SEA-AIDS Network, April 24, 1996

Posted in response to:

SEA-AIDS, April 10, 1996

From Clive Wing

Below are excerpts from an article I wrote for The Act [not included], the magazine of Action for AIDS, Singapore, on the Chiang Mai AIDS conference. A previous posting offered some suggestions for the Manila conference. This expands some of them. The last paragraph is probably the most important. 

I believe the Manila conference should concentrate on the social, cultural and educational aspects of HIV infection in the region. Further, because one rarely sees scientists, sociologists and volunteers talking to each other on the same platform the conference presents an opportunity for them to integrate our existing knowledge for a blueprint which can guide and focus our efforts in the coming years. All we've been able to harvest from previous world and regional conferences are discrete proposals which may reflect the interests of the proponent rather than infected and uninfected citizens of Asia.

Thank you for your time.

Clive Wing

SEA-AIDS, April 22, 1996

From Alessio Panza, EC AIDS

Clive Wing in his e-mail (10 April 96) [containing the article he wrote for ACT] says that at the Chiang Mai Conference he did not notice studies on "keeping free from HIV, partners of HIV+ people". He maybe interested to know of two small such studies:

  1. Mindell Seidlin et al., "Heterosexual transmission of HIV in a cohort of couples in New York City", AIDS 1993, 71247-1254.

  2. Isabelle De Vincenzi, "A longitudinal study of human immunodeficiency virus transmission by heterosexual partners". The New England Journal of Medicine, Vol.331, No.6, August 11, 1994.

Dr. De Vincenzi found that 124 discordant couples, who consistently used condoms in about 15,000 episodes of intercourse, never transmitted HIV to partners (in spite of unprotected oral sex). Conversely, 121 couples, who did not use condoms consistently, had a seroconversion of 5% per 100 persons per year. Condoms do seem to protect discordant couples.

I hope somebody can give Clive Wing, and us all, references to more recent articles on this subject which is of relevance to the ever increasing number of discordant stable couples in countries, like Thailand, where heterosexual transmission is by far the main mode of HIV infection.

Dr. Alessio Panza

EC AIDS Coordination Unit, Bangkok

R.R. Frerichs Posting

Clive Wing (April 10, 1996) and Dr. Alessio Panza (April 22, 1996) have focused on the importance of programs to keep partners of HIV infected persons free of infection. If others are interested, I am including 10 articles and their abstracts that address this issue, to be included as a stored text file entitled, "Research on HIV transmission in heterosexual couples."

1. Dublin, S., Rosenberg, P.S., and Goedert, J.J. Patterns and predictors of high-risk sexual behavior in female partners of HIV-infected men with hemophilia. Aids 6(5):475-482, 1992.

OBJECTIVE: To characterize and quantify high-risk heterosexual activity in HIV-discordant couples. DESIGN: Analysis of cross- sectional and longitudinal questionnaire data from 217 HIV- negative female sexual partners of HIV-infected hemophilic men. METHODS: Comparison of prevalence rates of anal sex, oral sex, vaginal intercourse with or without condoms, and use of other contraceptives between 1985 and 1991. Logistic regression analysis of demographic, sexual and clinical variables to predict unprotected vaginal sex. Actuarial estimates of semi-annual relapse rates to unsafe sex. RESULTS: The proportion of women at low risk increased from 7 to 69% between 1985 and 1991, mainly because more women were condoms during all acts of vaginal intercourse. Other contraceptive practices did not change during this time. The proportion engaging in oral or anal sex decreased (from 26 to 13% and 13 to 4%, respectively). Unprotected vaginal sex was more common among women who enrolled earlier, had less education, engaged in oral or anal sex, and among those whose partners had not had AIDS. Unprotected vaginal sex before enrollment was the strongest predictor of this high-risk activity during follow-up. Two-year rates of relapse to high-risk behavior were significantly higher among women who enrolled at high risk compared with those who enrolled at low risk (39 versus 8%, P = 0.005). CONCLUSIONS: Although high-risk sexual behavior became much less prevalent in this population between 1985 and 1991, many continued to have unprotected vaginal sex occasionally. Counseling efforts should target couples who have been the most sexually active or have less education, and should emphasize not only initial risk reduction but also maintenance of low-risk.

2. Allen, S., Tice, J., Van de Perre, P., Serufilira, A., Hudes, E., Nsengumuremyi, F., Bogaerts, J., Lindan, C., and Hulley, S. Effect of serotesting with counselling on condom use and seroconversion among HIV discordant couples in Africa. British Medical Journal 304:1605-1609, 1992.

OBJECTIVE -- To determine whether HIV testing and counselling increased condom use and decreased heterosexual transmission of HIV in discordant couples. DESIGN -- Prospective study. SETTING -- Kigali, the capital of Rwanda. SUBJECTS -- Cohabiting couples with discordant HIV serology results. MAIN OUTCOME MEASURES--Condom use in the couple and HIV seroconversion in the negative partners. RESULTS -- 60 HIV discordant couples were identified, of whom 53 were followed for an average of 2.2 years. The proportion ofdiscordant couples using condoms increased from 4% to 57% after one year of follow up. During follow up two of the 23 HIV negative men and six of the 30 HIV negative women seroconverted (seroconversion rates of 4 and 9 per100 person years). The rate among women was less than half that estimated for similar women in discordant couples whose partners had not been serotested. Condom use was less common among those who seroconverted (100%v 5%, p = 0.01 in men; 67% v 25%, p = 0.14 in women). CONCLUSIONS - - Roughly one in seven cohabiting couples in Kigali have discordant HIV serological results. Confidential HIV serotesting with counselling caused a large increase in condom use and was associated with a lower rate of new HIV infections. HIV testing is a promising intervention for preventing the spread of HIV in African cities.

3. Kennedy, C.A., Skurnick, J., Wan, J.Y., Quattrone, G., Sheffet, A., Quinones, M., Wang, W., and Louria, D.B. Psychological distress, drug and alcohol use as correlates of condom use in HIV-serodiscordant heterosexual couples. Aids 7(11):1493-1499, 1993.

OBJECTIVE: To investigate the relationship between psychological distress, alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. METHODS: Structured interviews were conducted to collect demographic information, detailed data on psychological distress, drug and alcohol use and sexual behavior. RESULTS: Analyses were based on 106 pairs of sexually active discordant couples. Significant differences among heterosexual condom users and non-users varied according to gender and HIV serostatus. Affect domains of interpersonal sensitivity and hostility were significant, as were the variables of regular drug or alcohol use combining sex with drugs or alcohol. Employment was strongly associated with condom use in HIV-negative women whose regular sexual partners were HIV-positive men. CONCLUSION: The risk of vaginal sex without condoms in HIV-serodiscordant heterosexual couples may be reduced by specific psychological counseling and attention to drug and alcohol use as risk factors. Further research on the effect of employment of HIV-negative women is required.

4. Padian, N.S., O'Brien, T.R., Chang, Y., Glass, S., and Francis, D.P. Prevention of heterosexual transmission of human immunodeficiency virus through couple counseling. Journal of Acquired Immune Deficiency Syndromes 6(9):1043-1048, 1993.

In the absence of an effective vaccine, behavior change remains the most effective means to prevent the spread of HIV. We examined behavior change over time and rates of HIV seroconversion in a cohort of HIV individuals and their heterosexual partners recruited since 1985. Participants were recruited from various HIV counseling and testing sources throughout California and were usually interviewed and tested in their own homes. Couple counseling and risk assessments were conducted at average intervals of six months. Data from 144 couples who were discordant for HIV serostatus are reported. Of the index cases, 78% were men. Most male index cases were bisexuals, and most female index cases were infected through heterosexual intercourse with a previous sexual partner. The mean duration of the relationship for the couple at intake was 5.6 years. Both condom use and sexual abstinence increased over time (p < 0.001 for both), and most behavior change occurred between intake and first follow-up visit. We observed no seroconversion after 193 couple-years of follow-up. Couple counseling in combination with social support appears to be an effective means to promote and sustain behavior change among HIV-infected individuals and their heterosexual partners.

5. Saracco, A., Musicco, M., Nicolosi, A., Angarano, G., Arici, C., Gavazzeni, G., Costigliola, P., Gafa, S., Gervasoni, C., Luzzati, R., Peccinino, F., Puppo, F., Salassa, B., Sinicco, A., Stellini, R., Terelli, U., Turbessi, G., Vigevani, G.M., Visco, G., Zerboni, R., and Lazzarin, A. Man-to-woman sexual transmission of HIV: longitudinal study of 343 steady partners of infected men. Journal of Acquired Immune Deficiency Syndromes 6(5):497-502, 1993.

To study incidence and risk factors of heterosexually transmitted HIV infection, we followed a cohort of 343 seronegative women, stable, monogamous partners of infected men whose only risk of acquiring HIV was sexual exposure to the infected partner. Nineteen seroconversions occurred in 529.6 person years (py) of observation, yielding an incidence rate of 3.6 per 100 py. The incidence rate was 7.2 per 100 py among women who did not always use or never used condoms and 1.1 among those who always used them [relative risk (RR) 6.6, 95% confidence interval (CI) 1.9-21.9]. Anal sex was associated with a risk increase in only those women not always using condoms (RR 1.4, 95% CI 0.4-4.8). No seroconversions were observed among 22 women using oral contraceptives. One of the women using intrauterine devices seroconverted. In couples who did not always use condoms, seroconversions occurred more frequently in partners of men with symptomatic diseases, with a low CD4+ cell number (< 400 per mm3) or with a detectable p24 antigen. In couples not always using condoms and where the man had a low CD4+ cell count, the joint presence of blood viral antigens and AIDS symptoms conditioned a fivefold increased risk of seroconversion of the woman (RR 5.4, CI 1.4-20.3). At multivariate analysis, women with longer relationships (> or = 1 year) showed a lower risk of seroconversion (RR 0.3, CI 0.1-0.8), and those partners of men positive for p24 antigen in serum had an increased risk of seroconversion (RR = 4.0, CI 0.1-0.8).

6. Seidlin, M., Vogler, M., Lee, E., Lee, Y.S., and Dubin, N. Heterosexual transmission of HIV in a cohort of couples in New York City [published erratum appears in AIDS 1993 Nov;7(11): following 1541]. Aids 7:1247-1254, 1993.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

7. Foley, M., Skurnick, J.H., Kennedy, C.A., Valentin, R., and Louria, D.B. Family support for heterosexual partners in HIV-serodiscordant couples. Aids 8(10):1483-1487, 1994.

OBJECTIVE: To ascertain the extent of family member support to heterosexual HIV-serodiscordant couples, and to identify associated sociodemographic and clinical characteristics. DESIGN: Discordant couples enrolled in a cohort study of heterosexual HIV transmission were interviewed with structured questionnaires to obtain sociodemographic data,family member awareness of HIV and perceived support from family members. Clinical characteristics were established by medical history, physical examination and laboratory tests. RESULTS: Awareness and support of family members were associated with sex of family member and HIV seropositivity, sex, education, and race of the partner. HIV- seropositive partners were more likely to have a sister aware than were HIV-negative partners (P = 0.01). More educated HIV- positive partners had fewer aware family members than less educated HIV-positive individuals (P = 0.02). Mothers ofHIV- positive women were more often aware than mothers of all other partners (P = 0.04). Black HIV-negative partners had fewer aware family members than whites or Hispanics (P = 0.02). CONCLUSION: This research shows both encouraging and disturbing patterns of family awareness of HIV and support to serodiscordant partners.

8. Nicolosi, A., Correa Leite, M.L., Musicco, M., Arici, C., Gavazzeni, G., and Lazzarin, A. The efficiency of male-to-female and female-to-male sexual transmission of the human immunodeficiency virus: a study of 730 stable couples. Italian Study Group on HIV Heterosexual Transmission [see comments]. Epidemiology. 5:570-575, 1994.

To compare the efficiency of male-to-female and female-to- male sexual transmission of human immunodeficiency virus (HIV), we studied 524 female partners of HIV-infected men and 206 male partners of HIV-infected women in 16 Italian clinical centers. All of the partners had had a sexual relationship with the index case lasting for at least 6 months and presented no other risk factor than sexual exposure to the HIV-infected partner. Among the 730 couples, 24% of the female partners were HIV positive, in comparison with 10% of the male partners. Using logistic regression analysis, including gender and controlling for condom use, frequency of intercourse, anal sex, partner's CD4+ cell count and clinical stage, sexually transmitted diseases, genital infections, and contraceptive use, we found that the efficiency of male-to-female transmission was 2.3 (95% confidence interval = 1.1-4.8) times greater than that of female-to-male transmission. Between-gender differences in the contact surfaces and the intensity of exposure to HIV during sexual intercourse are possible reasons for the difference in efficiency of transmission.

9. Nicolosi, A., Musicco, M., Saracco, A., and Lazzarin, A. Risk factors for woman-to-man sexual transmission of the human immunodeficiency virus. Italian Study Group on HIV Heterosexual Transmission. Journal of Acquired Immune Deficiency Syndromes 7(3):296-300, 1994.

A cross-sectional study of stable monogamous couples, recruited from16 clinical and surveillance centers in Italy between 1987 and 1992, was carried out to investigate the risk factors of woman-to-man sexual transmission of human immunodeficiency virus (HIV). The male partners of all HIV-infected women attending the centers were invited to participate in the study. Of the 275 male partners who were tested for HIV and interviewed with use of a structured questionnaire, 51 were excluded because they had other possible risk factor for HIV infection, no established risk factor was found in the index case, or they had stopped engaging in sexual intercourse. Fourteen of the 224 men (6.3%) were seropositive for HIV. At logistic regression, the highest risks of transmission were for men practicing peno-anal intercourse [odds ratio (OR), 4.6; 95% confidence interval (CI), 1.0-22.2] and for men whose partner had acquired immune deficiency syndrome (AIDS) or a CD4+ lymphocyte count of < or = 400/mm3. No seropositive men were observed among those who were aware of the woman's HIV seropositivity since the beginning of the relationship or were partners of a zidovudine-treated woman. The results suggest that the risk factors described in man-to-woman and man-to-man HIV sexual transmission also operate in woman-to- man transmission.

10. Guimaraes, M.D., Munoz, A., Boschi-Pinto, C., and Castilho, E.A. HIV infection among female partners of seropositive men in Brazil. Rio de Janeiro Heterosexual Study Group. American Journal of Epidemiology 142:538-547, 1995.

A heterosexual partner study was carried out in Rio de Janeiro, Brazil, from August 1990 to December 1991. The main objectives were to determine the rate of male-to-female transmission of human immunodeficiency virus (HIV) and to determine risk factors. Male index cases were recruited according to the following criteria: 1) confirmed HIV positivity, 2) 18 years old or older; 3) heterosexual contact within the past year. Only female partners who reported not to have other risk factors but to have had sexual contact with the index case were invited to participate. Couples were interviewed for risk factors and had blood collected for laboratory studies. The overall prevalence of HIV infection was 45 percent among 204 female partners in the study. Using logistic regression, the authors found the following factors to be independently (p < 0.05) associated with HIV infection: 1) anal sex (odds ratio (OR) = 3.74, 95% confidence interval (CI) 1.87-7.45); 2) condom use during vaginal sex sometimes (OR = 1.45, 95% CI 1.07-1.96), rarely (OR = 2.10, 95% CI 1.15-3.83), or never (OR = 3.04, 95% CI 1.23-7.50) as compared with always; 3) frequency of sexual contacts in the year prior to interview (100+) (OR = 2.00, 95% CI 1.03-3.91); and 4) oral contraceptive use (OR = 2.04, 95% CI 0.97-4.29). In addition to a borderline significance of oral contraceptive use, there was a strong suggestion of an interaction with history of sexually transmitted diseases.

Once married couples learn from HIV antibody testing that one partner is infected and the other is not, there is much that they can do to avoid transmission. The problems facing officials in developing countries are how to make such tests more widely available, how to educate discordant couples (i.e., one is a carrier and the other is not) on ways to prevent the virus from infecting the susceptible partner, and how to get communities to be more accepting of those found to be infected. 

The studies I have cited on heterosexual discordant couples offer many insights, including the importance of knowing your HIV status, always using condoms, practicing withdrawal before ejaculation, and avoiding anal sex. They do not, however, address how HIV testing should best be offered, or how HIV infected persons can appropriately be accepted and integrated into the community.