Francis Martinson

Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection

Objectives:This study was conducted to compare viral dynamics in blood and semen between subjects with antibody negative, acute HIV-1 infection and other subjects with later stages of infection. Design:A prospective cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic. Methods:Blood samples from HIV antibody negative or indeterminate volunteers were used to detect HIV RNA in plasma using a pooling strategy. Blood and seminal plasma HIV-1 RNA concentrations were measured over 16 weeks. Results:Sixteen men with acute HIV infection and 25 men with chronic HIV infection were studied. Blood viral load in subjects with acute HIV infection was highest about 17 days after infection (mean ± SE, 6.9 ± 0.5 log10 copies/ml), while semen viral load peaked about 30 days after infection (4.5 ± 0.4 log10 copies/ml). Semen viral load declined by 1.7 log10 to a nadir by week 10 of HIV infection. Semen and blood viral loads were more stable in chronically infected subjects over 16 weeks. Higher semen levels of HIV RNA were noted in subjects with low CD4 cell counts. Conclusions:These results provide a biological explanation for reported increases in HIV transmission during the very early (acute) and late stages of infection. Recognizing temporal differences in HIV shedding in the genital tract is important in the development of effective HIV prevention strategies.

The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: a modelling study

BACKGROUND HIV transmission risk is higher during acute and early HIV infection than it is during chronic infection, but the contribution of early infection to the spread of HIV is controversial. We estimated the contribution of early infection to HIV incidence in Lilongwe, Malawi, and predict the future effect of hypothetical prevention interventions targeted at early infection only, chronic infection only, or both stages. METHODS We developed a deterministic mathematical model describing heterosexual HIV transmission, informed by detailed behavioural and viral-load data collected in Lilongwe. We included sexual contact within and outside of steady pairs and divided the infectious period into intervals to allow for changes in transmissibility by infection stage. We used a Bayesian melding approach to fit the model to HIV prevalence data collected between 1987 and 2005 at Lilongwe antenatal clinics. We assessed interventions that reduced the per-contact transmission probability to 0.00003 in people receiving them, and varied the proportion of individuals receiving the intervention in each stage. FINDINGS We estimated that 38.4% (95% credible interval 18.6-52.3) of HIV transmissions in Lilongwe are attributable to sexual contact with individuals with early infection. Interventions targeted at only early infection substantially reduced HIV prevalence, but did not lead to elimination, even with 100% coverage. Interventions targeted at only chronic infections also reduced HIV prevalence, but coverage levels of 95-99% were needed for the elimination of HIV. In scenarios with less than 95% coverage of interventions targeted at chronic infections, additional interventions reaching 25-75% of individuals with early infection reduced HIV prevalence substantially. INTERPRETATION Our results suggest that early infection plays an important part in HIV transmission in this sub-Saharan African setting. Without near-complete coverage, interventions during chronic infection will probably have incomplete effectiveness unless complemented by strategies targeting individuals with early HIV infection. FUNDING National Institutes of Health, University of North Carolina Center for AIDS Research.

Concurrent sexual partnerships among women in the United States.

Background. The marked racial disparity in sexually transmitted infection (STI) rates in the United States remains inadequately explained. One important factor may be concurrent sexual partnerships (relationships that overlap in time), which can transmit STIs more rapidly through a population than does sequential monogamy. Methods. To determine prevalence, distribution, and correlates of U.S. women’s involvement in concurrent partnerships, we analyzed sexual partnership data reported by the 10,847 women, age 15–44 years, in the 1995 National Survey of Family Growth. Overlapping sexual partnership dates were determined by computer program and visual review of the data. Results. Prevalence of concurrent partnerships since January 1991 was 12% overall. Prevalence was lowest among currently married respondents (4%) and highest among those who were formerly married (22%), never married (19%), in the lowest income stratum (17%), age 18–24 years when interviewed (23%), or who first had sexual intercourse at age 12 or 13 (35%). Prevalence was 21% among blacks, 11% among whites, 8% among Hispanics, and 6% among Asian American and Pacific Islanders. Multiple logistic analysis substantially weakened the relationship between concurrency and black race (OR = 1.2; 95% CI = 1.1–1.4). Conclusions. Marital status in particular is strongly related to concurrency; thus, lower marriage rates among blacks and the associated higher concurrency of sexual partners may contribute to racial disparities in STI rates.

Heterosexually Transmitted Hiv Infection Among African Americans in North Carolina

Context: Rates of heterosexually transmitted HIV infection among African Americans in the southeastern United States greatly exceed those for whites. Objective: Determine risk factors for heterosexually transmitted HIV infection among African Americans. Methods: Population-based case-control study of black men and women, aged 18-61 years, reported to the North Carolina state health department with a recent diagnosis of heterosexually transmitted HIV infection and age- and gender-matched controls randomly selected from the state driver s license file. A lower-risk stratum of respondents was created to identify transmission risks among people who denied high-risk behaviors. Results: Most case subjects reported annual household income <

Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction

16,000, history of sexually transmitted diseases, and high-risk behaviors, including crack cocaine use and sex partners who injected drugs or used crack cocaine. However, 27% of case subjects (and 69% of control subjects) denied high-risk sexual partners or behavior. Risk factors for HIV infection in this subset of participants were less than high school education (adjusted odds ratio [OR] 5.0; 95% CI: 2.2, 11.1), recent concern about having enough food for themselves or their family (OR 3.7; 1.5, 8.9), and having a sexual partner who was not monogamous during the relationship with the respondent (OR 2.9; 1.3, 6.4). Conclusion: Although most heterosexually transmitted HIV infection among African Americans in the South is associated with established high-risk characteristics, poverty may be an underlying determinant of these behaviors and a contributor to infection risk even in people who do not have high-risk behaviors.

Social context of sexual relationships among rural African Americans.

Among the three recently described GB viruses (GBV‐A, GBV‐B, and GBV‐C), only GBV‐C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV‐C proteins, the prevalence of GBV‐C RNA in human sera was studied using reverse transcription‐polymerase chain reaction (RT‐PCR). The prevalence of GBV‐C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV‐C was frequently detected in residents of West Africa, where the prevalence was >10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV‐C RNA. In addition, GBV‐C RNA sequences were detected in individuals diagnosed with non‐A‐E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV‐C RNA more than 1 year after the initial positive result.

Concurrent Partnerships among Rural African Americans with Recently Reported Heterosexually Transmitted HIV Infection

Background Reasons for the strikingly increased rates of HIV and other sexually transmitted infections (STIs) among African Americans in the rural Southeastern United States remain unclear. Investigators have devoted little attention to the potential influence of the social and economic context on sexual behaviors. Goal To examine the potential influence of these contextual factors on behaviors that promote the transmission of STIs. Study Design Focus group interviews in which African Americans from rural North Carolina discussed life in their communities and contextual factors affecting sexual behavior. Results Respondents reported pervasive economic and racial oppression, lack of community recreation, boredom, and resultant substance abuse. Many perceived a shortage of black men because of their higher mortality and incarceration rates compared with whites, and believed this male shortage to be partly responsible for the concurrent sexual partnerships that they perceived as widespread among unmarried persons. Conclusion Contextual features including racism, discrimination, limited employment opportunity, and resultant economic and social inequity may promote sexual patterns that transmit STIs.

Frequent detection of acute primary HIV infection in men in Malawi.

Objectives To investigate concurrent sexual partnerships among African Americans in North Carolina with recently reported heterosexually transmitted HIV infection. Design Population-based case series of persons with newly reported HIV infection. Methods Household interviews concerning sexual and other risk behaviors for HIV transmission were conducted among African Americans, 18–59 years old, who had been reported to the state health department within the preceding 6 months as having heterosexually acquired HIV infection. Dates of sexual partnerships were analyzed to identify concurrency among the 3 most recent partnerships. Results Concurrency prevalence in the past 1 and 5 years, respectively, was 45 and 63% for men and 37 and 58% for women. Most respondents (87%) believed that a recent partner had had a concurrent partnership. Multivariate analysis revealed associations between concurrency and male gender, youth, crack cocaine smoking, and incarceration of a sex partner. Conclusions Concurrent partnerships likely accelerate heterosexual HIV transmission among blacks in the rural southeastern United States. Future research should examine the socioeconomic context that supports this network pattern.

Concurrent sexual partnerships among African Americans in the rural south.

Background: Acute (antibody-negative) HIV infection is associated with high transmission potential but is rarely recognized. Design: Cross-sectional study. Methods: We examined the prevalence and predictors of acute HIV infection among 1361 consecutive male outpatients attending sexually transmitted disease (STD; n = 929) and dermatology (n = 432) clinics in Lilongwe, Malawi. Serum specimens negative for HIV antibodies were screened by HIV RNA PCR using a highly specific pooling/resolution testing algorithm. Results: Five-hundred and fifty-three men (40.6%) were HIV antibody positive and 24 (1.8%) had acute HIV infection; 23 of 24 acutely infected men were from the STD clinic, where they represented 4.5% of all HIV antibody-negative men and 5.0% of all HIV infections. HIV RNA levels for acutely infected men were significantly higher [median (interquartile range), 6.10 (5.19–6.54) log10 HIV RNA copies/ml] than for 58 HIV antibody-positive men [4.42 (3.91–4.95) log10 copies/ml; P < 0.0001]. The factor most strongly associated with acute HIV infection was STD clinic attendance: (odds ratio, 15.2; 95% confidence interval, 2.04–113.0). In multivariate analysis considering only STD patients, factors associated with acute HIV infection included inguinal adenopathy, genital ulceration and age 24–26 years, the age stratum associated with peak incidence of HIV infection among Malawian men. Conclusions: Traditional HIV antibody tests alone are not sufficient to exclude HIV infection among men with acute STD in Malawi due to a surprising proportion of acute HIV infections in this population. Alternative screening methods are required for diagnosis of acute HIV infection; such screening could be important for research and for prevention of the sexual transmission of HIV in select populations.

The year-long effect of HIV-positive test results on pregnancy intentions, contraceptive use, and pregnancy incidence among Malawian women.

PURPOSE To investigate concurrent sexual partnerships among heterosexual African Americans, 18 to 59 years old, in rural North Carolina. METHODS Household interviews with persons randomly selected from the NC drivers license file were conducted to identify overlap among the 3 most recent sexual partnerships. RESULTS Concurrency prevalence in the past 5 years was 53% (men) and 31% (women). Most (61%) respondents believed that a recent partner had had a concurrent partnership. Multivariate analysis revealed strong associations between concurrency and male gender, being unmarried, age of sexual debut, and incarceration of a sex partner. CONCLUSIONS Concurrent partnerships may increase rates of heterosexual HIV among blacks in the rural Southeastern United States. Future research should examine the context that supports this network pattern.