Probability Of HIV Transmission Research Articles

Cost-effectiveness of childbirth strategies for prevention of mother-to-child transmission of HIV among mothers receiving nevirapine in India

Background:Mother-to-child transmission of HIV is an important mode of spread of HIV in India. With strategies like caesarian section and nevirapine therapy, this spread has been reduced. However, they have costs attached. In this context, this paper attempts to compare the cost-effectiveness of alternative childbirth strategies among HIV-positive mothers receiving nevirapine.Materials and Methods:Using sentinel surveillance data from three districts in Tamil Nadu, a model was created to test the cost-effectiveness of vaginal delivery against elective caesarian section among mothers receiving nevirapine. Sensitivity analysis was applied to evaluate cost per HIV infection prevented.Results:Vaginal delivery is not only cheaper in HIV-infected mothers receiving nevirapine but also cost-effective as compared to elective caesarian section. The incremental cost for preventing an additional HIV infection through caesarian section was Rs. 76,000. Sensitivity analysis reveals that the findings are robust over a range of HIV transmission probabilities, 0.04-0.14 for vaginal delivery and 0.00-0.02 for caesarian section.Conclusions:From a clinical perspective, the findings suggest that pregnant HIV-infected women receiving nevirapine should consider the benefits of a cheaper and safer vaginal delivery. From an economic perspective, the findings support the strategy of vaginal delivery in mothers receiving nevirapine.

Theorizing “Big Events” as a potential risk environment for drug use, drug-related harm and HIV epidemic outbreaks

Political-economic transitions in the Soviet Union, Indonesia, and China, but not the Philippines, were followed by HIV epidemics among drug users. Wars also may sometimes increase HIV risk. Based on similarities in some of the causal pathways through which wars and transitions can affect HIV risk, we use the term “Big Events” to include both. We first critique several prior epidemiological models of Big Events as inadequately incorporating social agency and as somewhat imprecise and over-generalizing in their sociology. We then suggest a model using the following concepts: first, event-specific HIV transmission probabilities are functions of (a) the probability that partners are infection-discordant; (b) the infection-susceptibility of the uninfected partner; (c) the infectivity of the infected—as well as (d) the behaviours engaged in. These probabilities depend on the distributions of HIV and other variables in populations. Sexual or injection events incorporate risk behaviours and are embedded in sexual and injection partnership patterns and community networks, which in turn are shaped by the content of normative regulation in communities. Wars and transitions can change socio-economic variables that can sometimes precipitate increases in the numbers of people who engage in high-risk drug and sexual networks and behaviours and in the riskiness of what they do. These variables that Big Events affect may include population displacement; economic difficulties and policies; police corruption, repressiveness, and failure to preserve order; health services; migration; social movements; gender roles; and inter-communal violence—which, in turn, affect normative regulation, youth alienation, networks and behaviours. As part of these pathways, autonomous action by neighbourhood residents, teenagers, drug users and sex workers to maintain their economic welfare, health or happiness may affect many of these variables or otherwise mediate whether HIV epidemics follow transitions. We thus posit that research on whether and how these interacting causal pathways and autonomous actions are followed by drug-related harm and/or HIV or other epidemics can help us understand how to intervene to prevent or mitigate such harms.

Filipino Men’s Condom Use During Gay Sex: Findings from the 2003 National Demographic and Health Survey

Filipino Men’s Condom Use During Gay Sex: Findings from the 2003 National Demographic and Health Survey

No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa

To estimate the role of each of the HIV progression stages in fueling HIV transmission in sub-Saharan Africa by using the recent measurements of HIV transmission probability per coital per HIV stage in the Rakai study. A mathematical model, parameterized by empirical data from the Rakai, Masaka, and Four-City studies, was used to estimate the proportion of infections due to each of the HIV stages in two representative epidemics in sub-Saharan Africa. The first setting represents a hyperendemic HIV epidemic (Kisumu, Kenya) whereas the second setting represents a generalized but not hyperendemic HIV epidemic (Yaoundé, Cameroon). We estimate that 17, 51, and 32% of HIV transmissions in Kisumu were due to index cases in their acute, latent, and late stages, respectively. In Yaoundé, the fractions were 25, 44, and 31%. We found that the relative contribution of each stage varied with the epidemic evolution with the acute stage prevailing early on when the infection is concentrated in the high-risk groups with the late stage playing a major role as the epidemic matured and stabilized. The latent stage contribution remained largely stable throughout the epidemic and contributed about half of all transmissions. No HIV stage dominated the epidemical though the latent stage provided the largest contribution. The role of each stage depends on the phase of the epidemic and on the prevailing levels of sexual risk behavior in the populations in which HIV is spreading. These findings may influence the design and implementation of different HIV interventions.

Probability of HIV Transmission During Acute Infection in Rakai, Uganda

Accurate estimates of the probability of HIV transmission during various stages of infection are needed to inform epidemiological models. Very limited information is available about the probability of transmission during acute HIV infection. We conducted a secondary analysis of published data from the Rakai, Uganda seroconversion study. Mathematical and computer-based models were used to quantify the per-act and per-partnership transmission probabilities during acute and chronic HIV infection, and to estimate how many of the transmission events reported in the Rakai study were due to acute-phase HIV transmission. The average per-act transmission probability during acute infection equaled 0.03604 vs. 0.00084 for chronic HIV infection. Overall, HIV was transmitted during acute infection in 46.5% of 23 "incident index partner couples." Acute-phase transmission accounted for 89.1% of all transmission events in the first 20 months of follow-up. These results highlight the substantial risk of transmission during acute HIV infection.

Highly efficient HIV transmission to young women in South Africa

Young women in sub-Saharan Africa are at very high risk of HIV acquisition, and high prevalence levels have been observed among women reporting one lifetime partner and few sexual contacts. Such findings have led to hypotheses that the probability of HIV transmission from men to women must be far higher than previously appreciated. We used the data from a cross-sectional national household survey of HIV among South African women aged 15-24 years to estimate the per-partnership transmission probability from men to women. Estimates were obtained using maximum likelihood methods and a transmission probability model allowing for random error in the self-reported number of lifetime partners. Sensitivity analyses were employed to assess the robustness of the per-partnership transmission probability estimates to the assumed HIV prevalence in male partners. HIV prevalence in women was 21.2% (95% confidence interval 17.9-24.5). The mean reported number of lifetime partners was 2.3. A significant increase in prevalence was observed with increasing lifetime partner numbers (P = 0.02). For a range of plausible values of the partner prevalence, the estimated per-partnership transmission probability varied from 0.74 to 1.00 with 95% confidence intervals ranging from 0.56 to 1.00. The per-partnership probability of HIV transmission from men to women in this population was very high. Before this, the majority of studies examining per-partnership transmission probabilities estimated values below 50%. Identifying the factors that may drive the efficient spread of HIV in sub-Saharan Africa is essential for the development of effective prevention interventions.

Male circumcision as a preventive measure limiting HIV transmission

From population based studies and couple studies, the probability of HIV transmission and acquisition has been associated with the blood and genital viral load, male circumcision, STDs, stage of disease, genetic haplotype, viral subtype, and levels of mucosal immune response. This presentation will review the relationship between male circumcision and HIV transmission and discuss policy implications in promoting circumcision as a prevention modality. A systematic meta-analysis of 38 studies, mostly in Africa, found that circumcised men appear to have a 50% or more reduction in HIV infection as uncircumcised men. A sub-analysis of 16 of these studies found a 70% reduction in HIV infection among higher-risk men. Mapping of the HIV epidemic has demonstrated a strong correlation between regions with higher rates of HIV infection and those with lower circumcision rates. A two-year cohort study of male partners of HIV-positive women in Rakai, Uganda, found that 40 of 137 uncircumcised men became infected compared to 0 of 50 circumcised men over 2.1 years(p = 0.0004). Biological explanations include greater ability of the internal foreskin to absorb HIV more efficiently due to the greater presence of Langerhans and other HIV target cells and its greater susceptibility to tears, abrasions, and consequently infection by STDs and HIV. One RCT in South Africa demonstrated that circumcision afforded a 61% (95% CI: 34%–77%) reduction in HIV incidence even after controlling for behavioral factors (Auvert et al., PLoS Medicine 2005;298). Two other RCT trials of male circumcision in Uganda and Kenya are in progress. In summary, these epidemiologic, biological, and clinical trial results provide very strong evidence that male circumcision significantly lowers the risk of HIV acquisition. Mathematical models of implementing male circumcision in countries with high incident rates suggest marked reductions in HIV incidence in men with subsequent decreased transmission rates to women. Policy implications of recommending male circumcision to populations in high-risk countries need to take into consideration cultural norms, religious traditions, national and local laws. Circumcision may represent one important biological intervention to decreasing the acquisition of HIV, but will need to be carefully integrated into other HIV prevention and STD control programs in order to prevent subsequent behavioral disinhibition among circumcised men.

The Surgeon and AIDS

Since the first reports on indications and outcome for abdominal procedures in the HIV/AIDS patient were published 20 years ago, the epidemiology and presentation of surgical illness have changed remarkably with the advent of new antiviral regimens. A review of the now occasional, but still important, role of the surgeon in contemporary treatment of HIV/AIDS is presented. Information was obtained by PubMed searches of medical journals, examination of reference lists, and Web resources. Articles on operative indications, outcomes, precautions, source of transmission, and pathophysiology of HIV/AIDS were selected. Data was obtained from peer-reviewed articles and references. The last 2 decades have seen a decrease in operative mortality from as high as 85% to approximately 15% with a corresponding improvement in morbidity. Surgical emergencies such as appendicitis occur in HIV patients with the same frequency as non-HIV patients and are treated with equivalent results. Concern about transmission of HIV in the operating room has lessened somewhat. Although still a hazard, the probability of HIV transmission with accidental exposure is low, with risks below 0.5% for percutaneous hollow-bore needles and less than 0.1% risk for mucus membrane exposure. Improved surgical outcomes together with of accurate data on the modes and likelihood of accidental transmission of HIV to members of the surgery team have resulted in the treatment of HIV/AIDS patients becoming an accepted part of routine surgical practice.

Preclinical Assessment of HIV Vaccines and Microbicides by Repeated Low-Dose Virus Challenges

BackgroundTrials in macaque models play an essential role in the evaluation of biomedical interventions that aim to prevent HIV infection, such as vaccines, microbicides, and systemic chemoprophylaxis. These trials are usually conducted with very high virus challenge doses that result in infection with certainty. However, these high challenge doses do not realistically reflect the low probability of HIV transmission in humans, and thus may rule out preventive interventions that could protect against “real life” exposures. The belief that experiments involving realistically low challenge doses require large numbers of animals has so far prevented the development of alternatives to using high challenge doses.Methods and FindingsUsing statistical power analysis, we investigate how many animals would be needed to conduct preclinical trials using low virus challenge doses. We show that experimental designs in which animals are repeatedly challenged with low doses do not require unfeasibly large numbers of animals to assess vaccine or microbicide success.ConclusionPreclinical trials using repeated low-dose challenges represent a promising alternative approach to identify potential preventive interventions.

GB virus C coinfection and vertical transmission in HIV‐infected mothers before the introduction of antiretroviral prophylaxis

To investigate the prevalence of GB virus C (GBV-C) viraemia and GBV-C antibodies in a cohort of HIV-infected mothers and their infants between 1987 and 1994. GBV-C viraemia and antibodies were determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in 52 HIV-infected mothers and their 53 infants, who were born before antiretroviral prophylaxis for reduction of HIV transmission was introduced at the end of 1994. Ten of these children acquired HIV. Mothers of three children had GBV-C viraemia and mothers of another 14 children carried antibodies against GBV-C. No mother had GBV-C antibodies and GBV-C viraemia simultaneously. GBV-C viraemia was detected in only one infant. This child was delivered by the vaginal route to a mother with GBV-C viraemia, and was not HIV-infected. No vertical transmission of GBV-C occurred from mothers with GBV-C antibodies. However, four of 10 children who were infected with HIV had a mother with past or ongoing GBV-C infection. Our findings suggest that the risk of vertical transmission of GBV-C is not elevated in HIV-infected mothers. Furthermore, although the number of HIV-1-infected children was low, we saw no evidence that the presence of ongoing or past GBV-C infection influenced the probability of vertical HIV transmission.

Stochastic simulation of the impact of antiretroviral therapy and HIV vaccines on HIV transmission; Rakai, Uganda.

To model the effects of antiretroviral therapy (ART) and HIV vaccines on HIV transmission using empirical data from studies in Rakai, Uganda. A stochastic simulation model estimated HIV incidence, probabilities of transmission per coital act and the reproductive number (R0) with ART and HIV vaccines. Model inputs included Rakai data on HIV transmission probabilities per coital act by HIV viral load, age and gender, and sexual behaviors. The impacts of therapy were derived from US programs, and vaccine assumptions included preventive efficacies ranging from 25 to 75%. Component projection models estimated the numbers of HIV-infected persons over 20 years. The model incidence [1.57/100 person years (PY)] closely fitted empirical data (1.5/100 PY). Simulations of ART using DHHS treatment guidelines, predicted declines in HIV incidence, but R0 remained > 1.0, and the numbers of HIV-positive persons did not change substantially over 20 years. Preventive vaccines with > 50% efficacy and > 50% population coverage could reduce R0 to < 1.0, and substantially reduce the number of HIV-infected persons over 20 years. Concurrent ART and a preventive vaccine can have substantial impact at lower levels of population coverage and would markedly reduce the HIV infected population over 20 years. However, behavioral disinhibition with increased numbers of sexual partners in either ART or vaccine recipients, increased HIV incidence and diminished intervention impact. ART alone cannot control the HIV epidemic in mature epidemics such as Rakai, and persons in need of therapy will increase over time. ART in combination with a low efficacy vaccine could control the epidemic, if behavioral disinhibition is prevented.

Improving safer sex measures through the inclusion of relationship and partner characteristics

This article describes the development of a safer sex algorithm, which considers the characteristics of a woman's relationship and the HIV risk profile of herself and her primary partner. A sample of 306 low-income, predominantly African American women was recruited to participate in a study of the effectiveness of a sexual health seminar. These women were interviewed three times, at one month prior to seminar administration, three months after the seminar and again nine months after the seminar. Data from these women indicate that using an algorithm that considers the probability of HIV transmission between partners decreases the measured prevalence of unsafe sex in this population by about 17% and lowers the estimate of the average number of unsafe incidents by about four incidents in three months. The algorithm results in measures with adequate levels of temporal stability, which are similar to the more commonly used measure, vaginal or anal intercourse without a condom.

The epidemiological and control implications of HIV transmission probabilities within partnerships.

The spread of HIV is in part determined by the probability of transmission within a sexual partnership. The goal of the study was to examine the relationship between the per-partnership and per-act transmission probability and explore how different assumptions influence the measurement of cofactors and interventions. We defined the mathematical relationship between the transmission probability of HIV per sex act and per partnership for the proposed biologic mechanisms. For completeness we included the original assumption of a per-partnership transmission probability and also the simple binomial model, which cannot be ruled out completely because of potential measurement error in discordant partner studies. A constant per-act or per-partnership transmission probability provides unsatisfactory models of the observed relationship between the number of sex acts and the likelihood of transmission. Either there is extreme heterogeneity in the transmission likelihood between partnerships or the transmission likelihood within a partnership decreases over time. These models cause the relative risk for a partnership in which a cofactor STD is present to decrease more rapidly than would be expected. The transmission probability per-partnership is substantially reduced only when there is a dramatic reduction in unprotected acts (e.g., condom use) or the transmission probability per act (e.g., due to antiretrovirals or STD treatment). Combining interventions can sometimes generate a more-than-additive impact, particularly with extreme heterogeneity. More empirical studies are needed to develop realistic models of transmission providing quantitative understanding of the HIV transmission process.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection.

The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

The multicentre study on factors determining the differential spread of HIV in four African cities: summary and conclusions.

In all regions of sub-Saharan Africa the predominant mode of transmission of HIV is through heterosexual intercourse however there are large variations in the rate and extent of the spread of HIV in different populations. This study was conducted to identify the factors that influence the rapid spread of HIV in four African cities namely Cotonou (Benin) Yaounde (Cameroon) Kisumu (Kenya) and Ndola (Zambia). Results demonstrated that high rates of partner change and being married are risk factors for HIV infection in men in at least one city but are risk factors for women in all four cities. In addition condom use among sex workers did not show a difference between the low and high prevalence cities. Furthermore no evidence of changes towards safer sexual behavior was identified in the high HIV prevalence cities. The only factors that were more common in the two high HIV prevalence cities than in the two low HIV prevalence cities were young age at first intercourse for women young age at first marriage and large age difference between the spouses. It was also noted that the high levels of HIV infection among young people especially among female adolescents in Kisumu and Ndola highlight the importance of interventions targeted at young people and their partners.

Modeling HIV risk.

To provide HIV risk estimates for specific local population subgroups using an HIV risk index combining HIV risk behaviors, prevalence rates, and transmission probabilities. A sample of 270 individuals was studied. Respondents described sexual and injection risk behaviors and partners in the previous 30 days. An HIV risk index was computed for each individual, combining reported sexual and injecting risk behaviors, HIV prevalence estimates for partners and HIV transmission probabilities for each of the risk behaviors. Partner HIV prevalence rates were estimated from a national sample, and HIV transmission probabilities were obtained from previously published studies. Projected risk estimates were found to differ a great deal within major demographic categories. Highest 10-year risk was found among African-American male gay injectors (72%) and the lowest among white male heterosexual noninjectors (<.01%). The method used here for estimating HIV risk can be calculated for specific at-risk population subgroups of any size and composition, including individuals. By understanding which specific subpopulations are at risk, specific interventions and public health campaigns may be better targeted.

Emerging HIV Infections With Distinct Subtypes of HIV-1 Infection Among Injection Drug Users From Geographically Separate Locations in Guangxi Province, China

Summary: Heroin users from Guangxi province, a southern province of China that borders Vietnam in the south and Yunnan province in China in the west, were studied for prevalence and risk factors for HIV-1 infection. Viral env sequences from HIV-1-positive individuals were also determined for subtypes of HIV-1. The overall HIV prevalence among 227 heroin users was 40%. Most had used drugs for ≤3 years. Sharing of injection equipment and unprotected sex were significantly associated with HIV-1 infection. Subtypes C and E HIV-1 were detected in infected heroin users and were sharply segregated in two geographic locations: only subtype C was found in a border city with Yunnan province, whereas only subtype E was found in a city bordering northern Vietnam. HIV-1 strains within each subtype were remarkably homogenous, with a mean intersubject DNA distance of 2.32% for subtype E and 1.13% for subtype C, respectively. Phylogenetic analysis of C2-V5 region of Guangxi subtype E env sequences revealed significant clustering with subtype E sequences from southern Vietnam and Cambodia. These results suggest that HIV-1 infection among heroin users in Guangxi represents two emerging epidemics initiated from distinct sources: one from Vietnam and another from Yunnan province. Factors associated with HIV-1 infection were not restricted to injection practices. Unprotected sexual behaviors are likely to increase the probability of HIV transmission beyond this high-risk population. Designing and implementing effective intervention strategies targeted toward both injection drug use and high risk sexual behavior are urgently needed to further reduce HIV-1 spread in China.

Emerging HIV infections with distinct subtypes of HIV-1 infection among injection drug users from geographically separate locations in Guangxi Province, China.

Heroin users from Guangxi province, a southern province of China that borders Vietnam in the south and Yunnan province in China in the west, were studied for prevalence and risk factors for HIV-1 infection. Viral env sequences from HIV-1-positive individuals were also determined for subtypes of HIV-1. The overall HIV prevalence among 227 heroin users was 40%. Most had used drugs for < or = 3 years. Sharing of injection equipment and unprotected sex were significantly associated with HIV-1 infection. Subtypes C and E HIV-1 were detected in infected heroin users and were sharply segregated in two geographic locations: only subtype C was found in a border city with Yunnan province, whereas only subtype E was found in a city bordering northern Vietnam. HIV-1 strains within each subtype were remarkably homogenous, with a mean intersubject DNA distance of 2.32% for subtype E and 1.13% for subtype C, respectively. Phylogenetic analysis of C2-V5 region of Guangxi subtype E env sequences revealed significant clustering with subtype E sequences from southern Vietnam and Cambodia. These results suggest that HIV-1 infection among heroin users in Guangxi represents two emerging epidemics initiated from distinct sources: one from Vietnam and another from Yunnan province. Factors associated with HIV-1 infection were not restricted to injection practices. Unprotected sexual behaviors are likely to increase the probability of HIV transmission beyond this high-risk population. Designing and implementing effective intervention strategies targeted toward both injection drug use and high risk sexual behavior are urgently needed to further reduce HIV-1 spread in China.

Centrality measures for disease transmission networks

This paper addresses the issue of the applicability of various network measures (provided by analysis programs such as UCINET) for the analysis of a disease transmission network. A simulation was conducted to estimate HIV transmission probabilities within an empirical network of cocaine injectors. The results of the simulation were then used as a criterion to evaluate network measures of disease vulnerability and infectivity. The analysis concludes that, for the type of disease transmission network studied, relatively simple ego-network-based network measures can be adequate to the measurement of vulnerability to disease and infectivity.

Mother-to-child transmission of HIV-1.

After reviewing the evidence on the relation of vertical transmission of HIV to stage of infection in the mother, I developed a stochastic model of transmission in which the probability of transmission per week is proportional to the virus load in the mother. The virus load in different stages of the infection is measured by viral RNA levels or tissue culture infectious virus levels in plasma. The constant of proportionality is assumed to be different for transmission during pregnancy, during parturition, and during breast-feeding. Using data on transmission from mothers who are in the primary stage of infection, I estimated the constant of proportionality and calculated the probability of transmission during pregnancy as a function of the time pregnancy starts in relation to the stage of the infection. For breast-feeding, I calculated the conditional probability of transmission by breast-feeding for 20 weeks, dependent on the infant escaping infection during pregnancy and parturition. As might be expected, the probabilities of transmission are highest if the mother is in the primary stage of infection or in late stages of the disease and is quite low when the mother is in the asymptomatic stage of the infection.