Program impact and potential pitfalls of multi-purpose technologies (MPTs) for HIV prevention and contraception.

The overlapping epidemics of HIV and unplanned pregnancy disproportionately affect adolescent girls and young women (AGYW) in sub-Saharan Africa. Prevailing dynamics driving benefits of any prevention method at the population level depend on: 1) population size, risk profile, and prevalence of method use, 2) method efficacy, and 3) method use-effectiveness. Adding a multi-purpose technology (MPT) to prevent HIV and pregnancy to this three-part equation results in scenarios that may enhance HIV population impact, even with methods that exhibit less than "perfect" method efficacy, by extending protection among existing users and attracting new users, resulting in greater population coverage. However, the interplay of epidemic drivers is complex and the greatest population benefit of such a MPT would be realized among those most at risk for HIV and pregnancy, and could be harmful if successful contraceptive users switch to a method with lower use-effectiveness. While MPTs are highly desired, and may offer considerable individual, population, and system-level public health benefits, there is no "magic bullet", nor single prevention method-MPT or otherwise-that will end the HIV epidemic nor fully resolve unmet need for family planning. All methods have inherent tradeoffs and women have varied reproductive and HIV prevention needs across their life course. Key programmatic features to maximize the potential of MPTs include offering them among a range of safe and effective methods with comprehensive information about their features allowing women to make a fully-informed method choice. Programmatic follow-up should support consistent and correct use to maximize use-effectiveness, and then monitor for potential untoward effects.

Attitudes Toward Gender-Based Violence Among Sexually Active Adult Men at High Risk for HIV in Rustenburg, South Africa.

Gender-based violence (GBV) toward women is widespread and has been associated with increased HIV risk. We investigated attitudes toward GBV among men living in Rustenburg, South Africa, who were enrolled in a longitudinal HIV incidence study. Participants were 18 to 49 years old, reported high risk sexual activity in the last 3 months, and were HIV-uninfected. Attitudes toward GBV were evaluated using responses to a five-item standardized questionnaire about men perpetrating physical violence on a female spouse; responses to each item were scaled from 1 (no agreement) to 4 (strong agreement) and summed. Total scores >10 were considered permissive toward GBV. Among the 535 men analyzed, nearly half (N = 229, 42.8%) had a GBV score >10. Being young (18-24 years) (adjusted odds ratio [aOR] = 1.53, 95% confidence interval [CI] [1.06, 2.22]), having less years of education (aOR = 1.61, 95% CI [1.11, 2.32]), and reporting no current sexual partner at baseline (aOR = 2.10, 95% CI [1.06, 4.14]) were independently associated with permissive attitudes toward GBV. The following behaviors reported in the last 3 months were also associated with high GBV scores: having a new female partner (aOR = 1.78, 95% CI [1.02, 3.10]), and having had an STI (aOR = 1.85, 95% CI [1.15, 2.99]). Consuming alcohol prior to sex in the last month (aOR = 1.59, 95% CI [1.09, 2.31]) was also associated with high GBV scores. A large proportion of South African HIV-uninfected men in this analysis reported permissive attitudes toward GBV. These attitudes were associated with HIV risk behavior. Integrating GBV and HIV prevention programs is essential.

High risk sexual behaviours associated with traditional beliefs about gender roles among men interested in medical male circumcision in South Africa.

BACKGROUND: Beliefs about gender roles and high-risk sexual behaviours underlie the human immunodeficiency virus (HIV) epidemic in South Africa. Yet, there is limited information on the relationships between beliefs about gender roles and risky sexual behaviours. Few studies have explored the association between beliefs about gender roles, high risk sexual behaviour, and health-seeking behaviour among men. METHODS: We investigated associations between gender beliefs (dichotomised as traditional or progressive) and high-risk sexual behaviour among South African men presenting for medical male circumcision (Apr 2014 to Nov 2015). RESULTS: Of 2792 enrolled men, 47.4% reported traditional gender beliefs. Participant ages ranged between 18-46 years (median age 26 years; interquartile range, 21-31 years). Most participants had at least one sex partner over the last 12 months (68.2%). Younger men (18-24 years old vs. 25-46 years old) (odds ratio [OR], 1.5 [95% confidence interval (CI) 1.0-2.0]), those with multiple partners ([OR], 1.5 (CI) 1.3-1.8]) and participants unsure of their last partner's HIV status (OR, 1.4 [95% CI 1.1-1.7]) were more likely to have traditional beliefs on gender roles. CONCLUSION: Young men with traditional beliefs on gender roles may be more likely to engage in high-risk sexual behaviour and could be good candidates for HIV prevention programmes. N = 206 (max 350) Trial registration Name of registry: Clinicaltrials.gov; Trial registration number: NCT02352961; Date of registration: 30 January 2015 "Retrospectively registered"; URL of trial registry record: https://www.clinicaltrials.gov/.

HIV incidence and predictors of inconsistent condom use among adult men enrolled into an HIV vaccine preparedness study, Rustenburg, South Africa.

INTRODUCTION: Understanding HIV incidence and risk behaviour among populations being considered for HIV vaccine studies is necessary for the appropriate design of trials. METHODS: Between May 2012 and June 2015, we recruited men aged 18-49 years from urban and peri-urban areas of Rustenburg, a mining town in the North West Province, South Africa. Men who reported HIV-risk behaviour were followed for nine to 12 months to determine HIV incidence and factors associated with condom use. RESULTS: A total of 400 HIV uninfected men were enrolled; 366 (91.5%) had at least one follow-up visit and were included in the analysis; 47.6% were under 25 years of age. HIV incidence was 1.9 per 100 person-years (95% CI: 0.79-4.56). Among heterosexual men (N = 339), 80.8% reported having vaginal intercourse with multiple partners in the past three months, among whom 74.1% reported inconsistent condom use. Sixty-eight percent reported vaginal intercourse with new female partners, of whom 40.6% reported inconsistent condom use. Over half (55.6%) of men who had sex with men (N = 27) reported anal intercourse with multiple male partners in the past three months, of whom 68.2% reported using condoms inconsistently. Men who had more than two female partners in the last three months (n = 121) were more likely to use condoms inconsistently (aOR 4.31, 95% CI: 1.34-13.8); in contrast, those with more than one new female sex partner (aOR 0.13, 94% CI 0.04-0.44), and whose sexual debut was after 19 years of age (aOR 0.39, 95% CI: 0.15-1.01) were less likely to use condoms inconsistently. CONCLUSION: HIV incidence was low and similar to other studies of heterosexual men in South Africa. To identify men at high risk for HIV for enrolment in prevention trials, future researchers may need to focus on those who report early sexual debut and who report having multiple sexual partners. Men in newer relationships appear to use condoms more frequently.

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection.

Few human immunodeficiency virus (HIV)-infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, "viral control") in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51-2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3-9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3-3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1-2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0-3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines.

Prediction of extended high viremia among newly HIV-1-infected persons in sub-Saharan Africa.

OBJECTIVE: Prompt identification of newly HIV-infected persons, particularly those who are most at risk of extended high viremia (EHV), allows important clinical and transmission prevention benefits. We sought to determine whether EHV could be predicted during early HIV infection (EHI) from clinical, demographic, and laboratory indicators in a large HIV-1 incidence study in Africa. DESIGN: Adults acquiring HIV-1 infection were enrolled in an EHI study assessing acute retroviral syndrome (ARS) symptoms and viral dynamics. METHODS: Estimated date of infection (EDI) was based on a positive plasma viral load or p24 antigen test prior to seroconversion, or the mid-point between negative and positive serological tests. EHV was defined as mean untreated viral load ≥5 log10 copies/ml 130-330 days post-EDI. We used logistic regression to develop risk score algorithms for predicting EHV based on sex, age, number of ARS symptoms, and CD4 and viral load at diagnosis. RESULTS: Models based on the full set of five predictors had excellent performance both in the full population (c-statistic = 0.80) and when confined to persons with each of three HIV-1 subtypes (c-statistic = 0.80-0.83 within subtypes A, C, and D). Reduced models containing only 2-4 predictors performed similarly. In a risk score algorithm based on the final full-population model, predictor scores were one for male sex and enrollment CD4<350 cells/mm3, and two for having enrollment viral load >4.9 log10 copies/ml. With a risk score cut-point of two, this algorithm was 85% sensitive (95% CI: 76%-91%) and 61% specific (55%-68%) in predicting EHV. CONCLUSIONS: Simple risk score algorithms can reliably identify persons with EHI in sub-Saharan Africa who are likely to sustain high viral loads if treatment is delayed. These algorithms may be useful for prioritizing intensified efforts around care linkage and retention, treatment initiation, adherence support, and partner services to optimize clinical and prevention outcomes.

Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

BACKGROUND: Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. METHODS: From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/µl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/µl or a single CD4 ≤350 cells/µl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. RESULTS: Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. CONCLUSIONS: In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission.

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

Four models of HIV counseling and testing: utilization and test results in South Africa.

BACKGROUND: HIV Counseling and Testing (HCT) is the point-of-entry for pathways of HIV care and prevention. However, HCT is not reaching many who are HIV infected and this may be related to the HCT provision model. We describe HCT utilization and HIV diagnosis using four models of HCT delivery: clinic-based, urban mobile, rural mobile, and stand-alone. METHODS: Using cross-sectional data from routine HCT provided in South Africa, we described client characteristics and HIV test results from information collected during service delivery between January 2009 and June 2012. RESULTS: 118,358 clients received services at clinic-based units, 18,597; stand-alone, 28,937; urban mobile, 38,840; and rural mobile, 31,984. By unit, clients were similar in terms of median age (range 28-31), but differed in sex distribution, employment status, prior testing, and perceived HIV risk. Urban mobile units had the highest proportion of male clients (52%). Rural mobile units reached the highest proportion of clients with no prior HCT (61%) and reporting no perceived HIV risk (64%). Overall, 10,862 clients (9.3%) tested HIV-positive. CONCLUSIONS: Client characteristics varied by HCT model. Importantly, rural and urban mobile units reached more men, first-time testers, and clients who considered themselves to be at low risk for HIV.

Pregnancy incidence and correlates in a clinical trial preparedness study, North West Province South Africa.

INTRODUCTION: Women in HIV prevention trials often must typically agree to avoid pregnancy. Regardless, some become pregnant. Screening tools predicting pregnancy risk could maximize trial safety and efficiency. OBJECTIVES: We assessed incidence and correlates of pregnancy among women at high HIV risk. METHODS: We enrolled sexually-active, HIV-negative women into an observational cohort (2008-2011). At enrollment demographic, contraceptive, reproductive, pregnancy intention and behavioural data were collected. Women reported if one or both partners wanted or intended for the couple to become pregnant. We measured gender role beliefs using a locally validated eight-point index. We tested HIV and pregnancy, and inquired about sexually transmitted infection symptoms (STIs) at enrollment and monthly. HIV testing included behavioural counselling and condom provision, but did not specifically counsel women to avoid pregnancy. Cox proportional hazard modelling evaluated the associations with pregnancy. The multivariate model included the following variables "Recent pregnancy attempts", "Gender Roles Beliefs", "Self-reported STIs" and "Age". RESULTS: We screened 1068 women and excluded (24.6%, 263/1068) who did not report risk behaviour. Non-pregnant, non-sterilized women aged 18-35 (median = 21 years) enrolled (n = 438). Most women reported one partner (74.7%) and a prior live birth (84.6%). Median follow-up time was 6 months (range 0.7-15.5). Pregnancy incidence was 25.1 per 100 women-years (n = 57 pregnancies). Conservative beliefs on gender roles (Adjusted Hazard Ratio (aHR) 1.8; 95% confidence interval [CI] 1.1-2.9), recent pregnancy attempts (aHR 1.9; 95% CI 1.1-3.4) and baseline self-reported STI (aHR 2.5; 95% CI 1.4-4.4) were associated with increased incident pregnancy. Report of no pregnancy intention was associated with lowered pregnancy risk (aHR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: We identified new and confirmed existing factors that can facilitate screening for pregnancy risk.

Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa.

OBJECTIVE: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs). DESIGN: Prospective cohort. METHODS: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/µl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS. RESULTS: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09). CONCLUSION: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.

Peer-education intervention to reduce injection risk behaviors benefits high-risk young injection drug users: a latent transition analysis of the CIDUS 3/DUIT study.

We analyzed data from a large randomized HIV/HCV prevention intervention trial with young injection drug users (IDUs) conducted in five U.S. cities. The trial compared a peer education intervention (PEI) with a time-matched, attention control group. Applying categorical latent variable analysis (mixture modeling) to baseline injection risk behavior data, we identified four distinct classes of injection-related HIV/HCV risk: low risk, non-syringe equipment-sharing, moderate-risk syringe-sharing, and high-risk syringe-sharing. The trial participation rate did not vary across classes. We conducted a latent transition analysis using trial baseline and 6-month follow-up data, to test the effect of the intervention on transitions to the low-risk class at follow-up. Adjusting for gender, age, and race/ethnicity, a significant intervention effect was found only for the high-risk class. Young IDU who exhibited high-risk behavior at baseline were 90% more likely to be in the low-risk class at follow-up after the PEI intervention, compared to the control group.

Pregnancy incidence and correlates during the HVTN 503 Phambili HIV vaccine trial conducted among South African women.

BACKGROUND: HIV prevention trials are increasingly being conducted in sub-Saharan Africa. Women at risk for HIV are also at risk of pregnancy. To maximize safety, women agree to avoid pregnancy during trials, yet pregnancies occur. Using data from the HVTN 503/"Phambili" vaccine trial, we report pregnancy incidence during and after the vaccination period and identify factors, measured at screening, associated with incident pregnancy. METHODS: To enrol in the trial, women agreed and were supported to avoid pregnancy until 1 month after their third and final vaccination ("vaccination period"), corresponding to the first 7 months of follow-up. Unsterilized women, pooled across study arms, were analyzed. Poisson regression compared pregnancy rates during and after the vaccination period. Cox proportional hazards regression identified associations with first pregnancy. RESULTS: Among 352 women (median age 23 yrs; median follow-up 1.5 yrs), pregnancy incidence was 9.6/100 women-years overall and 6.8/100 w-yrs and 11.3/100 w-yrs during and after the vaccination period, respectively [Rate Ratio = 0.60 (0.32-1.14), p = 0.10]. In multivariable analysis, pregnancy was reduced among women who: enrolled at sites providing contraception on-site [HR = 0.43, 95% CI (0.22-0.86)]; entered the trial as injectable contraceptive users [HR = 0.37 (0.21-0.67)] or as consistent condom users (trend) [HR = 0.54 (0.28-1.04)]. Compared with women with a single partner of HIV-unknown status, pregnancy rates were increased among women with: a single partner whose status was HIV-negative [HR = 2.34(1.16-4.73)] and; 2 partners both of HIV-unknown status [HR = 4.42(1.59-12.29)]. Women with 2 more of these risk factors: marijuana use, heavy drinking, or use of either during sex, had increased pregnancy incidence [HR = 2.66 (1.24-5.72)]. CONCLUSIONS: It is possible to screen South African women for pregnancy risk at trial entry. Providing injectable contraception for free on-site and supporting consistent condom use may reduce incident pregnancy. Screening should determine the substance use, partnering, and HIV status of both members of the couple for both pregnancy and HIV prevention. TRIAL REGISTRATION: SA National Health Research Database DOH-27-0207-1539; Clinicaltrials.gov NCT00413725.

Agents of change: peer mentorship as HIV prevention among HIV-positive injection drug users.

This paper presents a qualitative investigation of peer mentoring among HIV seropositive injection drug users in a randomized controlled trial, the INSPIRE study. Qualitative analyses of 68 in-depth open-ended interviews conducted in 2005 in Baltimore, New York, Miami, and San Francisco revealed that these individuals conceptualized themselves as change agents through the identity of peer mentor at the three related domains of individual, interpersonal, and community-level change. Implications for program development and future research of peer mentoring as a mechanism for HIV prevention are discussed. This study was funded by the Centers for Disease Control and Prevention and Health Resources and Services Administration (HRSA).

HIV incidence and prevalence among cohorts of women with higher risk behaviour in Bloemfontein and Rustenburg, South Africa: a prospective study.

OBJECTIVES: The primary objective was to measure HIV incidence in two prospective cohorts of HIV-negative women. Secondary objectives included measuring pregnancy rates and participant retention rates. DESIGN: Cross-sectional HIV screening of women selected for higher risk behaviours, with a subsequent prospective study of uninfected women, followed monthly for up to 6 months. SETTING: Clinics established for research purposes in Bloemfontein and Rustenburg, South Africa. PARTICIPANTS: The authors enrolled women 18-35 years old and presumed at higher risk of sexual acquisition of HIV as indicated by self-reported sexual behaviour or recent sexually transmitted infection symptoms. In Bloemfontein, 1364 women were screened, 1154 were eligible for HIV testing and 1145 agreed to be tested. The prospective study enrolled 401 HIV-negative women. In Rustenburg, 946 women were screened, 540 were eligible and underwent HIV testing and 223 HIV-negative women entered the prospective study. PRIMARY AND SECONDARY OUTCOMES: Baseline prevalences of HIV infection and HIV incidence rates in the prospective cohorts, according to a double rapid test algorithm with a third rapid test for discrepant or indeterminate results. Pregnancy prevalences and pregnancy incidence rate in Bloemfontein. Participant retention rates in the prospective cohort until the study end. RESULTS: In Bloemfontein, 1145 women were tested, 391 entered follow-up and 92.3% of participants completed six study visits. In Rustenburg, 540 women were tested, 194 entered follow-up and retention up to the point of early study termination was 88.6%. Overall HIV prevalence was 21.2% (95% CI 18.9% to 23.6%) in Bloemfontein and 23.5% (95% CI 19.9% to 27.1%) in Rustenburg. Overall HIV incidence was 5.5/100 person-years (95% CI 2.5 to 10.4) in Bloemfontein and 3.0/100 person-years (95% CI 0.4 to 10.8) in Rustenburg. Cross-sectional pregnancy prevalences were 6.5% in Bloemfontein and 8.6% in Rustenburg. CONCLUSIONS: The authors observed substantial HIV incidence rates in both cohorts. Vigorous prevention efforts are needed in these smaller cities.

Perceived peer safer sex norms and sexual risk behaviors among substance-using Latino adolescents.

We investigated the association between perceived peer norms and safer sexual behaviors among substance using Latino youth. Between 2005 and 2006, cross-sectional data were collected from 92 Latino adolescents recruited from clinic- and community-based settings in two U.S. cities. Separate multivariate logistic regression models were used to assess the relationship between perceived peer norms around safer sex and two different outcomes: consistent condom use and multiple sexual partnerships. Among these participants, perceived peer norms encouraging safer sex were associated with consistent condom use even after controlling for individual- and partner-related factors. Perceived peer norms supporting safer sex were inversely associated with recently having two or more sexual partners after controlling for demographic characteristics. Perceived peer norms around safer sexual behavior contribute to a lower likelihood of engaging in two HIV/STI risk behaviors: inconsistent condom use and multiple partnering. These findings suggest that further development of peer-based interventions for Latino youth is warranted.

Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study.

BACKGROUND: The MRKAd5 HIV-1 gag/pol/nef subtype B vaccine was designed to elicit T-cell-mediated immune responses capable of providing complete or partial protection from HIV-1 infection or a decrease in viral load after acquisition. We aim to assess the safety and efficacy of the vaccine in South Africa, where the major circulating clade is subtype C. METHODS: We did a phase 2b double-blind, randomised test-of-concept study in sexually active HIV-1 seronegative participants at five sites in South Africa. Randomisation was by a computer-generated random number sequence. The vaccine and placebo were given by intramuscular injection on a 0, 1, 6 month schedule. Our coprimary endpoints were a vaccine-induced reduction in HIV-1 acquisition and viral-load setpoint. These endpoints were assessed independently in the modified intention-to-treat (MITT) cohort with two-tailed significance tests stratified by sex. We assessed immunogenicity by interferon-γ ELISPOT in peripheral-blood mononuclear cells. After the lack of efficacy of the MRKAd5 HIV-1 vaccine in the Step study, enrolment and vaccination in our study was halted, treatment allocations were unmasked, and follow-up continued. This study is registered with the South Africa National Health Research Database, number DOH-27-0207-1539, and ClinicalTrials.gov, number NCT00413725. FINDINGS: 801 of a scheduled 3000 participants, of whom 360 (45%) were women, were randomly assigned to receive either vaccine or placebo. 445 participants (56%) had adenovirus serotype 5 (Ad5) titres greater than 200, and 129 men (29%) were circumcised. 34 MITT participants in the vaccine group were diagnosed with HIV-1 (incidence rate 4·54 per 100 person-years) and 28 in the placebo group (3·70 per 100 person-years). There was no evidence of vaccine efficacy; the hazard ratio adjusted for sex was 1·25 (95% CI 0·76-2·05). Vaccine efficacy did not differ by Ad5 titre, sex, age, herpes simplex virus type 2 status, or circumcision. The geometric mean viral-load setpoint was 20,483 copies per mL (n=33) in the vaccine group and 34,032 copies per mL (n=28) in the placebo group (p=0·39). The vaccine elicited interferon-γ-secreting T cells that recognised both clade B (89%) and C (77%) antigens. INTERPRETATION: The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine. FUNDING: The US National Institute of Allergy and Infectious Disease and Merck and Co Inc.

Is injection serosorting occurring among HIV-positive injection drug users? Comparison by injection partner's HIV status.

Research needs to build evidence for the roles that HIV status of injection partners may or may not play in injection risk behaviors of injection drug users (IDUs). Using baseline data collected from a randomized controlled study (INSPIRE) conducted in four cities (Baltimore, Miami, New York, and San Francisco) from 2001 to 2005, we categorized 759 primarily heterosexual HIV-positive IDUs into four groups based on HIV serostatus of drug injection partners. Thirty-two percent of the sample injected exclusively with HIV-positive partners in the past 3 months and more than 60% had risky injection behavior with these partners. Eight percent injected exclusively with HIV-negative partners and 49% injected with any unknown status partners. The remaining 11% reported having both HIV-positive and -negative injection partners, but no partners of unknown HIV status. Riskier injection behavior was found among the group with mixed status partners. The risk among the group with any unknown status partners appeared to be driven by the greater number of injection partners. No major group differences were observed in socio-demographic and psychosocial factors. Our analysis suggests that serosorting appeared to be occurring among some, but not an overwhelming majority of HIV-positive IDUs, and knowledge of HIV status of all injection partners per se did not appear to be as important as knowledge of sexual partner's HIV status in its association with risk behavior.

Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention.

BACKGROUND & AIMS: Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption. METHODS: Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels, and change in alcohol use post-intervention. RESULTS: Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88). CONCLUSIONS: Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.