[show abstract][hide abstract] ABSTRACT: Tenofovir-emtricitabine (TDF-FTC) pre-exposure prophylaxis (PrEP) has been found to be effective for prevention of HIV infection in several clinical trials. Two studies of TDF PrEP among men who have sex with men showed slight bone mineral density (BMD) loss. We investigated the effect of TDF and the interaction of TDF and hormonal contraception on BMD among HIV-uninfected African men and women.
We evaluated the effects on BMD of using daily oral TDF-FTC compared to placebo among heterosexual men and women aged 18-29 years enrolled in the Botswana TDF2 PrEP study. Participants had BMD measurements at baseline and thereafter at 6-month intervals with dual-energy X-ray absorptiometry (DXA) scans at the hip, spine, and forearm.
A total of 220 participants (108 TDF-FTC, 112 placebo) had baseline DXA BMD measurements at three anatomic sites. Fifteen (6.8%) participants had low baseline BMD (z-score of <-2.0 at any anatomic site), including 3/114 women (2.6%) and 12/106 men (11.3%) (p = 0.02). Low baseline BMD was associated with being underweight (p = 0.02), having high blood urea nitrogen (p = 0.02) or high alkaline phosphatase (p = 0.03), and low creatinine clearance (p = 0.04). BMD losses of >3.0% at any anatomic site at any time after baseline were significantly greater for the TDF-FTC treatment group [34/68 (50.0%) TDF-FTC vs. 26/79 (32.9%) placebo; p = 0.04]. There was a small but significant difference in the mean percent change in BMD from baseline for TDF-FTC versus placebo at all three sites at month 30 [forearm -0.84% (p = 0.01), spine -1.62% (p = 0.0002), hip -1.51% (p = 0.003)].
Use of TDF-FTC was associated with a small but statistically significant decrease in BMD at the forearm, hip and lumbar spine. A high percentage (6.8%) of healthy Batswana young adults had abnormal baseline BMD Further evaluation is needed of the longer-term use of TDF in HIV-uninfected persons.
PLoS ONE 01/2014; 9(3):e90111. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thirty years after the beginning of the HIV epidemic, gay, bisexual, and other men who have sex with men (collectively called MSM) bear a disproportionate burden of HIV in the United States and continue to acquire a distressingly high number and proportion of new infections. Historically, HIV prevention for MSM has been focused on individual-level behavior change, rarely intervening with MSM as part of a couple. Yet, an estimated 33-67 % of HIV infections among MSM are acquired from primary sexual partners, suggesting that work with MSM as couples could be an important contributor to prevention. Given the emergence of high impact combination HIV prevention, it is timely to consider how work with the broad variety of male couples can improve both personal and community health. Couples HIV testing and counseling for MSM is an important advance for identifying men who are unaware that they are HIV-positive, identifying HIV-discordant couples, and supporting men who want to learn their HIV status with their partner. Once men know their HIV status, new advances in biomedical prevention, which can dramatically reduce risk of HIV transmission or acquisition, allow men to make prevention decisions that can protect themselves and their partners. This paper highlights the present-day challenges and benefits of using a couples-based approach with MSM in the era of combination prevention to increase knowledge of HIV status, increase identification of HIV discordant couples to improve targeting prevention services, and support mutual disclosure of HIV status.
Archives of Sexual Behavior 11/2013; · 3.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Little is known about HIV pre-exposure prophylaxis (PrEP) acceptability among men who have sex with men (MSM) in Thailand. The authors recruited an online convenience sample of Thai MSM (n = 404) to assess the knowledge of and interest in PrEP. Less than 7% had heard of PrEP; however, 35% indicated interest in PrEP after an explanation of its possible efficacy. Regression modeling demonstrated that HIV knowledge and risk behavior, but not demographics, are significant predictors of PrEP interest. More information and education about PrEP is necessary and more research is needed to examine PrEP acceptability and to inform the message for PrEP uptake.
Journal of the International Association of Providers of AIDS Care. 05/2013;
[show abstract][hide abstract] ABSTRACT: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain.
We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants.
A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03).
Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).
New England Journal of Medicine 07/2012; 367(5):423-34. · 51.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: To implement biomedical and other intensive HIV prevention interventions cost-effectively, busy care providers need validated, rapid, risk screening tools for identifying persons at highest risk of incident infection.
To develop and validate an index, we included behavioral and HIV test data from initially HIV-uninfected men who have sex with men who reported no injection drug use during semiannual interviews in the VaxGen VAX004 study and Project Explore HIV prevention trials. Using generalized estimating equations and logistic regression analyses, we identified significant predictors of incident HIV infection, then weighted and summed their regression coefficients to create a risk index score.
The final logistic regression model included age, and the following behaviors reported during the past 6 months: total number of male sex partners, total number of HIV-positive male sex partners, number of times the participant had unprotected receptive anal sex with a male partner of any HIV status, number of times the participant had insertive anal sex with an HIV-positive male partner, whether the participant reported using poppers, and whether they reported using amphetamines. The area under the receiver operating characteristic curve was 0.74, possible scores on index range from 0 to 47 and a score ≥10 had as sensitivity of 84% and a specificity of 45%, levels appropriate for a screening tool.
We developed an easily administered and scored 7-item screening index with a cutoff that is predictive of HIV seroconversion in 2 large prospective cohorts of US men who have sex with men. The index can be used to prioritize patients for intensive HIV prevention efforts (eg, preexposure prophylaxis).
[show abstract][hide abstract] ABSTRACT: Prevalence of HIV infection in Botswana is among the highest in the world, at 23.9% of 15 - 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana. Community members associated many positive benefits with home-based, door-to-door HIV testing, including convenience, confidentiality, capacity to increase the number of people tested, and opportunities to increase knowledge of HIV transmission, prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict, coercion, stigma, and psychological distress within households. Community members emphasised the need for individual and community preparation, including procedures to protect confidentiality, provisions for psychological and social support, and links to appropriate services for HIV-positive persons.
SAHARA J: journal of Social Aspects of HIV/AIDS Research Alliance / SAHARA , Human Sciences Research Council 12/2011; 8(4):171-8. · 0.81 Impact Factor
[show abstract][hide abstract] ABSTRACT: Approximately half of HIV-discordant heterosexual couples in the United States want children. Oral antiretroviral preexposure prophylaxis, if effective in reducing heterosexual HIV transmission, might be an option for discordant couples wanting to conceive. Couples should receive services to ensure they enter pregnancy in optimal health and receive education about all conception methods that reduce the risk of HIV transmission. In considering whether preexposure prophylaxis is indicated, the question is whether it contributes to lowering risk in couples who have decided to conceive despite known risks. If preexposure prophylaxis is used, precautions similar to those in the current heterosexual preexposure prophylaxis trials would be recommended, and the unknown risks of preexposure prophylaxis used during conception and early fetal development should be considered. Anecdotal reports suggest that oral preexposure prophylaxis use is already occurring. It is time to have open discussions of when and how preexposure prophylaxis might be indicated for HIV-discordant couples attempting conception.
American journal of obstetrics and gynecology 03/2011; 204(6):488.e1-8. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: Evaluations of the safety, effectiveness, and feasibility of HIV prevention interventions rely on self-reported sexual behaviour data. The accuracy of such data has sometimes been questioned. The absence of a so-called objective measure of sexual behaviour complicates this. Social desirability bias (SDB) is a key factor affecting the accuracy of self-reports. Individual, semi-structured interviews focusing on possible causes of and solutions to SDB were conducted with 30 Batswana women such as those who might enrol in planned vaginal microbicide trials. Respondents pointed to shame and the fear of public talk about them as key factors contributing to inaccurate self-reports, and they stressed the importance of privacy and confidentiality. Interviewer characteristics such as age, gender and personality were often viewed as likely to affect their candour. Alternative interviewing techniques such as audio computer-assisted self-interviewing (ACASI) were appealing to some for the potential to reduce embarrassment; others were sceptical. The possible implications for HIV-prevention research are presented.
African Journal of AIDS Research 11/2009; September 2006(Vol. 5):123-131. · 0.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: A process map is a diagram showing the sequential steps and decisions used to accomplish a procedure from start to finish. Process maps are a standard tool in continuous improvement efforts. They have not been used routinely in clinical trials although they are well suited to display trial processes.
We present the use of process maps as a tool to visualize and to monitor the correctness of trial work flows. We show that process maps can be used to assure that trial processes are conducted according to the SOP.
We describe how a process map is made. We then derive process maps from two sources: the SOP and trial procedures as currently implemented. We compare these maps to each other, using the SOP maps as the gold standard, to check that work is done according to the written procedures.
Eight process maps were produced from each source. 172 differences were found between the SOP maps and the walkthrough maps. Differences included the addition of extra steps, order errors, step mistakes, and ambiguities.
These process maps focused only on clinic procedures, so interactions with other trial components were not considered. The maps were made after the trial started, which may have biased their content and use.
Process maps are a simple tool to check if clinical trial processes are operating as designed and offer an effective means to identify and correct such divergences. Further research should focus on using process maps in the design phase of trials, analyzing the cost to benefit ratio for process maps, and linking the analysis of the process map to monitor queries to quantify the improvement gained from using this technique.
[show abstract][hide abstract] ABSTRACT: The most effective means of preventing human immunodeficiency virus (HIV) infection is preventing exposure. The provision of antiretroviral drugs to prevent HIV infection after unanticipated sexual or injection-drug--use exposure might be beneficial. The U.S. Department of Health and Human Services (DHHS) Working Group on Nonoccupational Postexposure Prophylaxis (nPEP) made the following recommendations for the United States. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be HIV infected, when that exposure represents a substantial risk for transmission, a 28-day course of highly active antiretroviral therapy (HAART) is recommended. Antiretroviral medications should be initiated as soon as possible after exposure. For persons seeking care < or =72 hours after nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person of unknown HIV status, when such exposure would represent a substantial risk for transmission if the source were HIV infected, no recommendations are made for the use of nPEP. Clinicians should evaluate risks and benefits of nPEP on a case-by-case basis. For persons with exposure histories that represent no substantial risk for HIV transmission or who seek care >72 hours after exposure, DHHS does not recommend the use of nPEP. Clinicians might consider prescribing nPEP for exposures conferring a serious risk for transmission, even if the person seeks care >72 hours after exposure if, in their judgment, the diminished potential benefit of nPEP outweighs the risks for transmission and adverse events. For all exposures, other health risks resulting from the exposure should be considered and prophylaxis administered when indicated. Risk-reduction counseling and indicated intervention services should be provided to reduce the risk for recurrent exposures.
MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control 02/2005; 54(RR-2):1-20.
[show abstract][hide abstract] ABSTRACT: Data from a prospective, multi-centred study of HIV infection in women (HIV Epidemiology Research Study [HERS]) was analysed to investigate the effect of continued injection drug use behaviours on progression to AIDS. All women enrolled in the HERS had at enrollment and at six-month intervals, a face-to-face interview which included specific injection drug use, a physical exam, and specimen collection that included T-cell subset analysis and HIV plasma RNA detection. Six hundred and thirty-nine HIV-infected women contributed 3021 person years of observation during 7.25 years of follow-up, and 299 of these women progressed to AIDS (46.8%). In multivariable analysis, there was no significantly increased risk of progression to AIDS for women reporting pre-baseline injection drug use [hazard ratio (HR)=1.07 (0.78, 1.47)] or reported injection drug use during follow-up [HR=0.89 (0.66, 1.21)] compared with never injecting. In a separate multivariable-model, comparing women who reported no injection in past six months to active injection drug users, the frequency of injection during the previous six months measured by daily injection [HR=0.97 (0.61, 1.55)] or less than daily injection [HR=0.84 (0.54, 1.33)] was not associated with progression to AIDS. Being in drug treatment was independently associated with a slower progression to AIDS [HR=0.41 (0.28, 0.59)]. Neither injection drug use, nor frequency of injection drug use was associated with progression to AIDS among HIV infected women. Initiation of antiretroviral therapy among drug users should be based on readiness for treatment rather than concern about faster progression.
International Journal of STD & AIDS 06/2004; 15(5):322-7. · 1.00 Impact Factor
[show abstract][hide abstract] ABSTRACT: HIV/AIDS-associated and non-HIV/AIDS-associated death rates and causes of death between 1993 and 1999 were examined in 885 HIV-infected women and 425 uninfected women of the HIV Epidemiology Research Study cohort. Causes of death were determined by review of death certificates and the National Death Index. Adjusted hazard ratios were calculated for mortality risk factors. In the 885 HIV-infected women and 425 uninfected women, 234 deaths and 8 deaths, respectively, occurred by December 31, 1999. All-cause death rates in the HIV-infected women were unchanged between the pre-HAART (1993-1996) and HAART eras (1997-1999)-5.1 versus 5.4 deaths per 100 person-years (py). AIDS as a cause of death decreased from 58% of all deaths in 1996 to 19% in 1999, while HAART use increased to 42% by the end of 1999. In spite of the modest proportion ever using HAART, HIV-related mortality rates did decline, particularly in women with CD4+ cell counts less than 200/mm(3). Drug-related factors were prominent: for the 129 non-AIDS-defining deaths, hepatitis C positivity (relative hazard [RH] 2.6, P <.001) and injection drug use (RH 1.7, P = 0.02) were strong predictors of mortality, but were not significant in the Cox model for 105 AIDS-defining deaths (RH 0.9, P >.30 and RH 0.7, P >.30, respectively. The regression analysis findings, along with the high percentage of non-AIDS deaths attributable to illicit drug use, suggest that high levels of drug use in this population offset improvements in mortality from declining numbers of deaths due to AIDS.
Journal of Urban Health 12/2003; 80(4):676-88. · 1.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: Viruses that can persist in the host are of special concern in immunocompromised populations. Among 871 human immunodeficiency virus (HIV)-infected and 439 high-risk HIV-uninfected women, seroprevalences of cytomegalovirus, hepatitis B virus, hepatitis C virus, and herpes simplex virus types 1 and 2 and prevalence of human papillomavirus DNA in cervicovaginal lavage fluids were all >50% and were 2-30 times higher than prevalences in the general population. Prevalences were highest among HIV-infected women, of whom 44.2% had >or=5 other infections, and were relatively high even among the youngest women (age 16-25 years). In multivariate analyses, viral infections were independently associated not only with behaviors such as injection drug use and commercial sex but also with low income, low levels of education, and black race. Disadvantaged women and women who engage in high-risk behaviors are more likely to be coinfected with HIV and other viruses and, thus, may be at high risk of serious disease sequelae.
The Journal of Infectious Diseases 05/2003; 187(9):1388-96. · 5.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women.
Prospective observational study.
One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month.
Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of > or = 88%, 28% of those with 45-87% adherence, 43% of those with 13-44% adherence, and 71% of those with < or = 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count.
Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.
AIDS 11/2002; 16(16):2175-82. · 6.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to determine the risk for urinary tract infection in women with or at risk for human immunodeficiency virus infection.
A prospective study of 871 women who were human immunodeficiency virus seropositive and 439 women who were human immunodeficiency virus seronegative was conducted, with additional semiannual interviews, human immunodeficiency virus serologic evaluation, human immunodeficiency viral load determination, T-cell subset test, urinalysis, pregnancy test, and selected quantitative urine culture examination.
At baseline, 26 women (3.0%) who were human immunodeficiency virus seropositive and 14 women (3.2%) who were human immunodeficiency virus seronegative women had urinary tract infections(P =.97). During 4280 person-years of follow-up, incident urinary tract infections was associated significantly with <12 years education (adjusted risk ratio, 1.43; 95% CI, 1.01-2.00), public assistance (adjusted risk ratio, 1.70; 95% CI, 1.11-2.60), pregnancy (adjusted risk ratio, 3.04; 95% CI, 2.04-4.53), and recent previous urinary tract infection (adjusted risk ratio, 1.82; 95% CI, 1.16-2.86), but not with human immunodeficiency virus infection. Among women who were human immunodeficiency virus seropositive, risk was associated with viral load (adjusted risk ratio, per log(10) increase 1.30; 95% CI, 1.03-1.63), but not with CD(4+) lymphocyte count.
Risk for urinary tract infection is not associated with human immunodeficiency virus infection but is associated with viral load among women who are infected with human immunodeficiency virus.
American Journal of Obstetrics and Gynecology 10/2002; 187(3):581-8. · 3.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate factors associated with use of HIV specialist care by women, and to determine whether medical indications for therapy validate lower rates of antiretroviral use in women not using HIV specialty care.
Cross-sectional analysis of the 1998 interview from the HIV Epidemiology Research Study (HERS) cohort.
Data from 273 HIV-infected women in the HERS were analyzed by multiple logistic regression to calculate predictors of the use of HIV specialist care providers. Variables included study site, age, education, insurance status, income, substance abuse, depression, AIDS diagnosis, CD4 + lymphocyte count, and HIV-1 viral load. In addition, medical indications for therapy and medical advice to begin antiretroviral therapy were assessed.
Of 273 women, 222 (81%) used HIV specialists and 51 (19%) did not. Having health insurance, not being an injection drug user, and being depressed were predictive of using HIV specialist care (all p < or = .05). Although medical indications for therapy in the two groups were comparable, the rate of highly active antiretroviral therapy (HAART) use was significantly higher in women using HIV specialist care (27%) compared with those not using HIV specialists (7.8%). Women using HIV specialists received significantly more advice to begin antiretroviral therapy (ART) in the 6 months prior to the interview compared with those not using specialists (relative risk, 2.4; 95% CI = 1.3-4.6).
Having insurance, not being an injection drug user, and being depressed all increased the likelihood of women receiving HIV specialty care, which, in turn, increased the likelihood of receiving recommended therapies. The level of HAART use (23%) and any ART use (47%) in these HIV-infected women was disturbingly low. Despite comparable medical indications, fewer women obtaining care from other than HIV specialists received HAART. These data indicate substantial gaps in access to HIV specialist care and thereby to currently recommended antiretroviral treatment.