Biologic factors in the sexual transmission of human immunodeficiency virus

The probability that any single episode of genital-genital or anogenital sexual intercourse will result in transmission of HIV may be determined by multiple biologic factors of the infectious person, the virus itself, and the exposed susceptible person. Some of these factors are known or suspected (figure 1), and they may explain observed differences in the sexual transmission of HIV in different parts of the world, notably in Africa, where genital ulcerative disease is probably influencing the epidemiology of HIV. Several studies have shown that infection in partners of HIV-infected persons is not determined solely by numbers of sexual encounters; on the contrary, HIV-infected partners have usually had fewer sexual encounters with infectious mates than have noninfected partners. Thus, sexually active persons should be cautioned that, to our knowledge, there are no nonsusceptible persons and that any single unprotected sexual encounter may lead to HIV transmission. Research into biologic factors that modulate HIV transmission continues to be hampered by difficulties in identifying HIV transmitters and nontransmitters, infective and noninfective variants of HIV (if the latter exist in vivo), and persons relatively more or less susceptible to HIV infection. However, as the number of partner studies and the number of those enrolled in them increase, a progressively clearer idea of the biologic determinants of sexual transmission of HIV should emerge.     

Cofactors in male-female sexual transmission of human immunodeficiency virus type 1

In a study of human immunodeficiency virus type 1 (HIV-1)-uninfected African prostitutes, 83 (67%) of 124 seroconverted to HIV-1. Oral contraceptive use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.6; P less than .03), genital ulcers (mean annual episodes, 1.32 +/- 0.55 in seroconverting women vs. 0.48 +/- 0.21 in seronegative women; P less than .02) and Chlamydia trachomatis infections (OR, 3.6; CI, 1.3-11.0; P less than .02) were associated with increased risk of HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR, 0.11; CI, 0.05-0.27; P less than .0001). Stepwise logistic regression analysis confirmed independent associations between HIV-1 infection and oral contraceptive use, condom use, genital ulcers, and C. trachomatis. The presence of other sexually transmitted diseases may in part explain the heterosexual HIV-1 epidemic in Africa and may represent important targets for intervention to control HIV-1 infection.     

Heterosexual transmission of human immunodeficiency virus infection - Strategies for prevention

In Canada, over 90% of the acquired immune deficiency syndrome cases diagnosed so far have been acquired sexually, with an increasing proportion made up of heterosexual contacts of high risk individuals. In multiple studies, the transmission rate among steady heterosexual partners of infected individuals has been variable. It is likely that complex biological and epidemiological interactions exist between human immunodeficiency virus (HIV) and sexually transmitted diseases with respect to transmission and disease. Other important determinants in transmission of infection may relate to the virus itself. The importance of sexual practices other than vaginal intercourse (such as anal intercourse) in the heterosexual transmission of HIV has not been well studied. The major approach to the control of HIV-associated disease remains the control of primary infection. Sexual practices which are the major epidemiological determinants of HIV transmission can be successfully modified by appropriate educational interventions. The promotion of condom use must form a special part of these interventions. Results of ongoing trials should be available prior to the formulation of recommendations for the use of spermicides. Targeted education programs may allow us to make better use of our resources in a more efficient way. In Canada, groups that could be reached by such programs include: prostitutes and their clients; men and women attending sexually transmitted disease clinics; sexually active women attending family planning clinics; and children and adolescents who are becoming sexually active.     

Heterosexual transmission of human immunodeficiency virus infection �C Strategies for prevention

In Canada, over 90% of the acquired immune deficiency syndrome cases diagnosed so far have been acquired sexually, with an increasing proportion made up of heterosexual contacts of high risk individuals. In multiple studies, the transmission rate among steady heterosexual partners of infected individuals has been variable. It is likely that complex biological and epidemiological interactions exist between human immunodeficiency virus (HIV) and sexually transmitted diseases with respect to transmission and disease. Other important determinants in transmission of infection may relate to the virus itself. The importance of sexual practices other than vaginal intercourse (such as anal intercourse) in the heterosexual transmission of HIV has not been well studied. The major approach to the control of HIV-associated disease remains the control of primary infection. Sexual practices which are the major epidemiological determinants of HIV transmission can be successfully modified by appropriate educational interventions. The promotion of condom use must form a special part of these interventions. Results of ongoing trials should be available prior to the formulation of recommendations for the use of spermicides. Targeted education programs may allow us to make better use of our resources in a more efficient way. In Canada, groups that could be reached by such programs include: prostitutes and their clients; men and women attending sexually transmitted disease clinics; sexually active women attending family planning clinics; and children and adolescents who are becoming sexually active.     

Mucosal transmission of human immunodeficiency virus

Since the beginning of the AIDS pandemic, and following the discovery of the human immunodeficiency virus (HIV) as the etiological agent of the disease, it was clear that the virus gains access to the human host predominantly through the mucosal tissue after sexual exposure. As a consequence, the female genital tract (vaginal and cervical), as well as the rectal, penile, and oral mucosae have been extensively studied over the last thirty years towards a better understanding of--and to develop strategies to prevent--sexual HIV transmission. This review seeks to describe the biology of the events leading to HIV infection through the human mucosa and introduce some of the approaches attempted to prevent the sexual transmission of HIV.     

The provision of safe blood--policy issues in the prevention of human immunodeficiency virus transmission.

The AIDS epidemic has focused attention on the constraints and deficiencies present in many blood transfusion services in the developing world. We discuss a variety of options for reducing transfusion-related HIV transmission, and suggest how new transfusion strategies may be implemented. We show that a transfusion service cannot rely solely on the screening of donor blood for anti-HIV antibodies and that a more comprehensive approach is needed. Important components of this approach include donor selection and improved clinical practice, in which blood and blood products are prescribed only when really necessary.     

Rectal transmission of human immunodeficiency virus type 1 to chimpanzees

Inoculation of chimpanzees with human immunodeficiency virus type 1 (HIV-1) has been used as a model system to define mechanisms of pathogenesis and to test protective efficacy of candidate HIV-1 vaccines. In most of these studies, the animals were inoculated intravenously. However, because HIV-1 is transmitted primarily across mucosal surfaces, future evaluations of vaccines should employ mucosal routes for administering infectious virus to immunized animals. To develop a model of rectal transmission of HIV-1, chimpanzees were exposed without trauma to 4 different HIV-1 strains at doses ranging from 200 to 10,000 TCIDs. Infection, characterized by seroconversion and repeated isolation of virus from lymphocytes, was established in 1 of 5 animals. This animal was sequentially inoculated with a subtype B and then an E strain and was infected with both strains. The results show that rectal exposure of adult chimpanzees to cell-free HIV-1 was not an efficient mode of transmission in this cohort.     

Heterosexual human immunodeficiency virus transmission among the middle class

Patterns of heterosexual human immunodeficiency virus (HIV) spread among the middle class have not been previously reported. Thirty-nine (35 women and four men) heterosexual contacts of HIV-infected individuals were evaluated by a private infectious diseases practice located in a predominantly white middle-class borough of New York City. Thirty-five of 39 patients were white. The mean household income of all patients was +41,200. Source cases (28 men and four women) were predominantly intravenous drug abusers (IVDAs). After excluding those contacts who were referred because of HIV or hepatitis B virus infection, six of 27 women and one of three men who agreed to be tested were seropositive for HIV. Heterosexual HIV spread is occurring among the middle class, with the predominant sources being IVDAs who do not fit the stereotype of being minorities and lower class. Condoms were not regularly utilized in these relationships even though (1) 23 of 32 contacts became aware of their partners' risk behaviors before the diagnosis of HIV infection, and (2) 23 of 32 IVDAs had attended a methadone program. Such programs could be better utilized to provide HIV-related education since they provide access to many of these IVDAs.     

人类免疫缺陷病毒在夫妻间传播的调查

目的了解AIDS高发区HIV在夫妻间的传播情况及相关因素，为预防HIV传播提供依据。方法对某AIDS高发区一方HIV抗体阳性的346对夫妻逐户进行流行病学横断面调查，采集其配偶的静脉血检测HIv抗体，对70例HIV感染者进行HIV前病毒DNA序列测定。结果346对夫妻中，发生夫妻间传播99对，传播率为28．6％。其中，一方因有偿供血感染的夫妻125对，发生夫妻间传播18对，传播率为14．4％；一方因受血感染的夫妻135对，发生夫妻间传播32对，传播率为23．7％；婚外性接触而感染的夫妻86对，发生夫妻间传播49对，传播率为57．0％。其中．丈夫传给妻子37对，传播率为69．8％；妻子传给丈夫12对，传播率为36．4％，男传女概率高于女传男（P〈0．01）。婚外性接触的感染者比血源性感染者有更高的夫妻传播率（P〈0．01）。检测30例血源性感染者均为B’亚型，9例发生夫妻传播，其配偶也均为B’亚型；31例婚外性接触感染者．AE亚型20例，07BC重组亚型8例，B亚型2例，B’亚型1例，检测其中发生夫妻传播8对，双方同属一个亚型（5对夫妻均为AE亚型，3对均为07BC重组亚型）；基因树显示夫妻的病毒同属一支。结论HIV感染正由高危人群向一般人群扩散，加强相关措施预防HIV在家庭内进一步传播很有必要。性传播疾病及HIV亚型可能在HIV的夫妻传播及男传女的传播中发挥作用。     

Cost-effectiveness of postexposure prophylaxis after sexual or injection-drug exposure to human immunodeficiency virus

BACKGROUND: The cost-effectiveness of interventions that provide human immunodeficiency virus (HIV) postexposure prophylaxis (PEP) to individuals after sexual or injection-drug use exposures depends on the distribution of exposure routes, prevalence of infection among source partners, adherence to PEP regimens, medical care costs, and prevailing epidemiologic contexts, among other factors. OBJECTIVE: To determine the cost-effectiveness of a comprehensive program to prevent HIV infection after sexual or injection-drug use exposure for 401 persons seeking PEP in an urban community. METHODS: We conducted a retrospective cost analysis to evaluate the cost of the PEP intervention, then combined this information with model-based effectiveness estimates to determine the PEP program's "cost-utility ratio," which is the ratio of net program costs to the total number of quality-adjusted life-years (QALYs) saved by the program. RESULTS: The average cost of the PEP regimen was $1222, and the total cost of the program was $450 970. The PEP program prevented an estimated 1.26 HIV infections, saved 11.74 QALYs, and averted $281 323 in future HIV-related medical care costs. The overall cost-utility ratio was $14 449 per QALY saved. When analysis was restricted to men reporting receptive anal intercourse, the savings in averted HIV-related medical care costs exceeded the cost of the program. The results were generally robust to changes in key parameter values but were sensitive to assumptions about the HIV transmission probability for receptive anal intercourse. CONCLUSIONS: For this study population, HIV PEP was cost-effective by conventional standards and cost-saving for persons seeking PEP after male-male receptive anal intercourse.     

Effect of immediate neonatal zidovudine on prevention of vertical transmission of human immunodeficiency virus type 1.

OBJECTIVE: To describe the effects of various short zidovudine (ZDV) prophylactic regimens on vertical transmission of human immunodeficiency virus type 1 (HIV-I) infection, especially the effect of immediate neonatal ZDV prophylaxis. MATERIALS AND METHODS: The study included children of HIV-1-infected mothers who were born at a teaching hospital in Bangkok. The ZDV prophylaxis regimens varied by time periods that included: (1) no ZDV (1991-1996); (2) antenatal oral ZDV, 250 mg given twice a day starting at 34 to 36 weeks gestation and continued until labor (1995-1998); (3) antenatal oral ZDV plus immediate neonatal oral ZDV, 6 mg/0.6 mL/dose started within the first 2 hours after birth and continued at 6-hour intervals for 4 to 6 weeks (1997-1998); and (4) intrapartum intravenous ZDV given in addition to regimen 3 (1998-1999). Neonatal ZDV was administered within 2 hours after birth in 95% of the neonates. RESULTS: In a cohort of 136 children born at least 9 months before the analysis date, the HIV-1 vertical infection rates were: (1) no ZDV, 11 of 48 (22.9%, 95% confidence interval [CI] = 12.0-37.3); (2) late antenatal ZDV, 10 of 47 (21.3%, 95% CI = 10.7-35.7); (3) late antenatal ZDV plus immediate neonatal ZDV, 0 of 28 (0%, 95% CI = 0-12.3); (4) late antenatal, intrapartum intravenous ZDV, plus immediate neonatal ZDV, 0 of 13 (0%, 95% CI = 0-24.7). An estimated 0% (95% CI = 0-8.6) of the infants who received immediate neonatal ZDV with or without intrapartum ZDV were infected, as compared with 22.1% (95% CI = 14.2-31.8 ) of those who received no ZDV or only late antenatal ZDV (P < 0.001). CONCLUSIONS: The results of this study suggests high protective effect of immediate administration of neonatal ZDV. Perinatal components of antiretroviral prophylaxis provided the best results for protecting against vertical HIV-1 transmission.     

Adaptive changes after human immunodeficiency virus type 1 transmission

Primary HIV-1 infection (PHI) is associated with a period of viremia, the resolution of which generally coincides with the development of both humoral and cellular immune responses. In this study replication-competent quasispecies were derived from virus isolated from an individual before and after seroconversion. Virus was also isolated from the presumed donor. Phenotypic and genotypic analysis of biological clones identified transmission of an R5/M-tropic phenotype. However, the ability of clones derived from the recipient to replicate in primary macrophages and PBMCs was restricted after transmission. This apparent selection process was supported by analysis of molecular clones derived from the isolated virus. Analysis of the ratio of synonymous and nonsynonymous substitutions predicted the existence of selective pressure soon after transmission, coincident with the development of HIV-1-specific antibodies. An Env trans-complementation assay demonstrated that the infectivity of a clone derived from the recipient after seroconversion was enhanced in the presence of a selected neutralizing antibody, indicating that the developing humoral immune response may have at least in part contributed to the selective pressure identified.     

Heterosexual transmission of human immunodeficiency virus among intravenous drug users

To examine sexual transmission of human immunodeficiency virus (HIV) among heterosexual intravenous drug users (IVDUs), HIV antibody status of IVDUs with intravenous drug-using sexual partners (IVSPs) was compared with that of IVDUs with no IVSPs. Initial bivariate analyses indicated IVDUs with IVSPs were more likely to be HIV antibody-positive than those with no IVSPs. Analyses by gender indicated that this relationship held for men but not women. IVDUs with IVSPs also differed from those without IVSPs demographically, in drug use, and in other sexual behaviors. When effects of other variables were controlled, no statistically significant relationship was found between injection history of sex partners and HIV status for the total sample or separately for men or women.     

Human genital epithelial cells capture cell-free human immunodeficiency virus type 1 and transmit the virus to CD4+ Cells: implications for mechanisms of sexual transmission

Sexual transmission of human immunodeficiency virus (HIV) accounts for the majority of new infections worldwide. However, the mechanism of viral transmission across the mucosal barrier is poorly understood. By use of an ectocervical epithelium-derived cell line, we found that the cells are capable of sequestering large amounts of HIV particles but are refractory to cell-free viral infection. The sequestered virus particles remained infectious for >/=6 days and resisted treatment with trypsin. Upon coculture with CD4(+)-susceptible cells, epithelial cells can effectively transmit the virus to these cells, which can result in robust infection of the target cells. Inhibitory studies have shown that heparan sulfate moiety of cell-surface proteoglycans is involved in the viral attachment to these CD4-negative epithelial cells. Genital epithelial cells may play active roles in sequestering, protecting, and transferring virus during sexual transmission of HIV.