Summary 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.
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.
A prospective ...cohort study was embedded within a cross-sectional study of HIV screening in a Lilongwe, Malawi STD clinic.
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.
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.
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.
In this randomized, controlled trial in Africa and India, combination antiretroviral therapy was more effective than standard therapy in preventing mother-to-child transmission of HIV but was ...associated with increased toxic effects.
Antiretroviral regimens used for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) have evolved from the first successful trial that used zidovudine single-drug prophylaxis in 1994 to current triple-drug regimens.
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Although there are clear benefits of combination antiretroviral therapy (ART) for the mother and infant, these do not come without risks; some studies have shown higher rates of adverse pregnancy outcomes with maternal ART than with regimens containing fewer antiretroviral agents.
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The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial compared the relative efficacy and safety of various proven antiretroviral strategies for the prevention of . . .
Individuals with acute (preseroconversion) HIV infection (AHI) are important in the spread of HIV. The identification of AHI requires the detection of viral proteins or nucleic acids with techniques ...that are often unaffordable for routine use. To facilitate the efficient use of these tests, we sought to develop a risk score algorithm for identifying likely AHI cases and targeting the tests towards those individuals.
A cross-sectional study of 1448 adults attending a sexually transmitted infections (STI) clinic in Malawi.
Using logistic regression, we identified risk behaviors, symptoms, HIV rapid test results, and STI syndromes that were predictive of AHI. We assigned a model-based score to each predictor and calculated a risk score for each participant.
Twenty-one participants (1.45%) had AHI, 588 had established HIV infection, and 839 were HIV-negative. AHI was strongly associated with discordant rapid HIV tests and genital ulcer disease (GUD). The algorithm also included diarrhea, more than one sexual partner in 2 months, body ache, and fever. Corresponding predictor scores were 1 for fever, body ache, and more than one partner; 2 for diarrhea and GUD; and 4 for discordant rapid tests. A risk score of 2 or greater was 95.2% sensitive and 60.5% specific in detecting AHI.
Using this algorithm, we could identify 95% of AHI cases by performing nucleic acid or protein tests in only 40% of patients. Risk score algorithms could enable rapid, reliable AHI detection in resource-limited settings.
Summary Background The RTS,S/AS01 malaria vaccine targets the circumsporozoite protein, inducing antibodies associated with the prevention of Plasmodium falciparum infection. We assessed the ...association between anti-circumsporozoite antibody titres and the magnitude and duration of vaccine efficacy using data from a phase 3 trial done between 2009 and 2014. Methods Using data from 8922 African children aged 5–17 months and 6537 African infants aged 6–12 weeks at first vaccination, we analysed the determinants of immunogenicity after RTS,S/AS01 vaccination with or without a booster dose. We assessed the association between the incidence of clinical malaria and anti-circumsporozoite antibody titres using a model of anti-circumsporozoite antibody dynamics and the natural acquisition of protective immunity over time. Findings RTS,S/AS01-induced anti-circumsporozoite antibody titres were greater in children aged 5–17 months than in those aged 6–12 weeks. Pre-vaccination anti-circumsporozoite titres were associated with lower immunogenicity in children aged 6–12 weeks and higher immunogenicity in those aged 5–17 months. The immunogenicity of the booster dose was strongly associated with immunogenicity after primary vaccination. Anti-circumsporozoite titres wane according to a biphasic exponential distribution. In participants aged 5–17 months, the half-life of the short-lived component of the antibody response was 45 days (95% credible interval 42–48) and that of the long-lived component was 591 days (557–632). After primary vaccination 12% (11–13) of the response was estimated to be long-lived, rising to 30% (28–32%) after a booster dose. An anti-circumsporozoite antibody titre of 121 EU/mL (98–153) was estimated to prevent 50% of infections. Waning anti-circumsporozoite antibody titres predict the duration of efficacy against clinical malaria across different age categories and transmission intensities, and efficacy wanes more rapidly at higher transmission intensity. Interpretation Anti-circumsporozoite antibody titres are a surrogate of protection for the magnitude and duration of RTS,S/AS01 efficacy, with or without a booster dose, providing a valuable surrogate of effectiveness for new RTS,S formulations in the age groups considered. Funding UK Medical Research Council.
Rates of heterosexually transmitted HIV infection among African Americans in the southeastern United States greatly exceed those for whites.
Determine risk factors for heterosexually transmitted HIV ...infection among African Americans.
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.
Most case subjects reported annual household income < $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).
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.
This was the first microbicide trial conducted in Africa to evaluate an antiretroviral-containing vaginal ring as an HIV prevention technology for women.
The trial assessed and compared the safety, ...acceptability and adherence to product use of a 4-weekly administered vaginal ring containing the antiretroviral microbicide, dapivirine, with a matching placebo ring among women from four countries in sub-Saharan Africa.
280 Healthy, sexually active, HIV-negative women, aged 18 to 40 years were enrolled with 140 women randomised to a dapivirine vaginal ring (25 mg) and 140 women to a matching placebo ring, inserted 4-weekly and used over a 12-week period. Safety was evaluated by pelvic examination, colposcopy, clinical laboratory assessments, and adverse events. Blood samples for determination of plasma concentrations of dapivirine were collected at Weeks 0, 4 and 12. Residual dapivirine levels in returned rings from dapivirine ring users were determined post-trial. Participant acceptability and adherence to ring use were assessed by self-reports.
No safety concerns or clinically relevant differences were observed between the dapivirine and placebo ring groups. Plasma dapivirine concentrations immediately prior to ring removal were similar after removal of the first and third ring, suggesting consistent ring use over the 12-week period. No clear relationship was observed between the residual amount of dapivirine in used rings and corresponding plasma concentrations. Self-reported adherence to daily use of the vaginal rings over the 12-week trial period was very high. At the end of the trial, 96% of participants reported that the ring was usually comfortable to wear, and 97% reported that they would be willing to use it in the future if proven effective.
The dapivirine vaginal ring has a favourable safety and acceptability profile. If proven safe and effective in large-scale trials, it will be an important component of combination HIV prevention approaches for women.
ClinicalTrials.gov NCT01071174.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Approximately 200,000 infants worldwide become infected with human immunodeficiency virus type 1 (HIV-1) annually through breast-feeding. In this randomized trial involving 2369 mother–infant pairs ...in Malawi, the use of either maternal antiretroviral therapy or infant nevirapine through the age of 6 months was found to significantly decrease the rate of maternal transmission of HIV-1 during breast-feeding.
Approximately 200,000 infants worldwide become infected annually with human immunodeficiency virus type 1 (HIV-1) through breast-feeding.
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Without treatment, half of these infants will die before their second birthday.
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Although formula feeding decreases the risk of postnatal HIV transmission, it is associated with an increased rate of early death.
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Thus, exclusive breast-feeding is recommended by the World Health Organization (WHO) for infants of HIV-1–positive women for the first 6 months of life in resource-limited settings.
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The use of antiretroviral drugs during pregnancy, labor, and delivery effectively reduces intrauterine and intrapartum HIV-1 transmission.
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However, without prophylaxis, an additional 9% . . .
OBJECTIVES:To estimate the effect of receiving HIV-positive test results on intentions to have future children and on contraceptive use and to assess the association between pregnancy intentions and ...pregnancy incidence among HIV-positive women in Malawi.
METHODS:Women of unknown HIV status completed a questionnaire about pregnancy intentions and contraceptive use and then received HIV voluntary counseling and testing (VCT). Women who were HIV-positive and not pregnant were enrolled and followed for 1 year while receiving HIV care and access to family planning (FP) services.
RESULTS:Before receiving their HIV test results, 33% of women reported a desire to have future children; this declined to 15% 1 week later (P < 0.0001) and remained constant throughout follow-up. Contraceptive use increased from 38% before HIV testing to 52% 1 week later (P < 0.0001) and then decreased to 46% by 12 months. The pregnancy incidence among women not reporting a desire to have future children after VCT was less than half of the incidence among women reporting this desire.
CONCLUSIONS:With knowledge of their HIV-positive status, women were less likely to desire future pregnancies. Pregnancy incidence was lower among women not desiring future children. Integration of VCT, FP, and HIV care could prevent mother-to-child HIV transmission.
Background. We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in ...Lilongwe, Malawi. Methods. After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50:5:1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. Results. A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. Conclusions. Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect ∼90% of acute cases.
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