Infected Partner Research Articles

Survey of HIV care providers on management of HIV serodiscordant couples – assessment of attitudes, knowledge, and practices

Human immunodeficiency virus (HIV) serodiscordant couples are at risk of sexual transmission of HIV between the infected and uninfected partner. We assessed New York area care providers for people living with HIV regarding attitudes, knowledge, and practice patterns toward fertility and conception in serodiscordant couples. Data were collected via a survey distributed in October 2013. Seventeen percent of respondents reported prescribing antiretroviral preexposure prophylaxis (PrEP) for a woman in a serodiscordant couple, and 38% percent of respondents reported having counseled serodiscordant couples on timed, unprotected intercourse without PrEP. Respondents who reported being “very” familiar with the data on HIV transmission in serodiscordant couples were more likely to report counseling their patients in timed, unprotected intercourse compared with those who reported less familiarity with the data (41% vs. 8%, p = 0.001). Although only 20% reported being “very” or “somewhat” familiar with the data on the safety of sperm washing with intrauterine insemination, those who did were more likely to have reported referring a patient for assisted reproductive technology (61% vs. 32%, p = 0.006). Effective patient counseling and referral for appropriate reproductive options were associated with knowledge of the literature pertaining to these options. This emphasizes the need for further provider education on reproductive options and appropriate counseling for serodiscordant couples.

Development, calibration and performance of an HIV transmission model incorporating natural history and behavioral patterns: application in South Africa.

Understanding HIV transmission dynamics is critical to estimating the potential population-wide impact of HIV prevention and treatment interventions. We developed an individual-based simulation model of the heterosexual HIV epidemic in South Africa and linked it to the previously published Cost-Effectiveness of Preventing AIDS Complications (CEPAC) International Model, which simulates the natural history and treatment of HIV. In this new model, the CEPAC Dynamic Model (CDM), the probability of HIV transmission per sexual encounter between short-term, long-term and commercial sex worker partners depends upon the HIV RNA and disease stage of the infected partner, condom use, and the circumcision status of the uninfected male partner. We included behavioral, demographic and biological values in the CDM and calibrated to HIV prevalence in South Africa pre-antiretroviral therapy. Using a multi-step fitting procedure based on Bayesian melding methodology, we performed 264,225 simulations of the HIV epidemic in South Africa and identified 3,750 parameter sets that created an epidemic and had behavioral characteristics representative of a South African population pre-ART. Of these parameter sets, 564 contributed 90% of the likelihood weight to the fit, and closely reproduced the UNAIDS HIV prevalence curve in South Africa from 1990–2002. The calibration was sensitive to changes in the rate of formation of short-duration partnerships and to the partnership acquisition rate among high-risk individuals, both of which impacted concurrency. Runs that closely fit to historical HIV prevalence reflect diverse ranges for individual parameter values and predict a wide range of possible steady-state prevalence in the absence of interventions, illustrating the value of the calibration procedure and utility of the model for evaluating interventions. This model, which includes detailed behavioral patterns and HIV natural history, closely fits HIV prevalence estimates.

Antiretroviral Treatment Scale-up Among Persons Living With HIV in Kenya

In 2007, 29% of HIV-infected Kenyans in need of antiretroviral therapy (ART), based on an immunologic criterion of CD4 ≤350 cells per microliter, were receiving ART. Since then, substantial treatment scale-up has occurred in the country. We analyzed data from the second Kenya AIDS Indicator Survey (KAIS 2012) to assess progress of treatment scale-up in Kenya. KAIS 2012 was a nationally representative survey of persons aged 18 months to 64 years that collected information on HIV status, care, and treatment. ART eligibility was defined based on 2 standards: (1) 2011 Kenya eligibility criteria for ART initiation: CD4 ≤350 cells per microliter or co-infection with active tuberculosis and (2) 2013 World Health Organization (WHO) eligibility criteria for ART initiation: CD4 ≤500 cells per microliter, co-infection with active tuberculosis, currently pregnant or breastfeeding, and infected partners in serodiscordant relationships. Blood specimens were tested for HIV antibodies and HIV-positive specimens tested for CD4 cell counts. Among 13,720 adults and adolescents aged 15-64 years, 11,626 provided a blood sample, and 648 were HIV infected. Overall, 58.8% [95% confidence interval (CI): 52.0 to 65.5) were eligible for treatment using the 2011 Kenya eligibility criteria and 77.4% (95% CI: 72.4 to 82.4) using the 2013 WHO eligibility criteria. Coverage of ART was 60.5% (95% CI: 50.8 to 70.2) using the 2011 Kenya eligibility criteria and 45.9% (95% CI: 37.7 to 54.2) using the 2013 WHO eligibility criteria. ART coverage has increased from 29% in 2007 to 61% in 2012. If Kenya adopts the 2013 WHO guidelines for ART initiation, need for ART increases by an additional 19 percentage points and current coverage decreases by an additional 15 percentage points, representing an additional 214,000 persons who will need to be reached.

ART for prevention: opportunities, challenges and predictions

Many antiretroviral agents (ARVs) concentrate in genital secretions. When provided to people with HIV these agents stop the transmission of the virus, presumably by i) reducing the concentration of virus and ii) bathing vulnerable tissues with ARVs during the potential transmission. In 11/13 observational studies ART reduced HIV transmission. In one observational study that included gay couples, treatment of the infected partner stopped transmission. In one randomized controlled trial (HPTN 052) of 17623 couples at 13 sites in 9 countries, documented suppression of viremia appears to have been 100% effective in prevention of HIV transmission. The maximal potential of ARVs for prevention of HIV requires universal early or immediate treatment, with good adherence to therapy. Currently only a few countries (including the US and Brazil) have guidelines leading to immediate treatment of infection. In addition, wider testing is required to identify HIV infected people who do not know their status. And new tests must be developed to detect acute HIV infection, a short stage of disease that contributes disproportionately to the spread of HIV. Earlier ART benefits the health of the HIV infected person: CD4 cells are restored to a high level, tuberculosis is averted, subtle changes in mentation are avoided, and normal lifespan is restored. While the biomedical benefits of early treatment of HIV have been established, logistical challenges of treatment-including early treatment-are considerable; and such logistical challenges compromise more immediate utilization of ARVs. It can be anticipated that universal immediate ART will become the standard of care in the near future. Commitment to simplifying treatment regimens and improving infrastructure is essential. In addition, HIV infected patients must be inspired to protect their own health through treatment. Ongoing confusion about when to start ART among patients and providers convinces asymptomatic people with HIV infection that delay of treatment has no adverse consequence, which does not appear to be the case in either short or long time frames. While treatment can be difficult, people who are not offered ARVs are often lost to follow-up. ARVs represent the cornerstone of combination HIV prevention; optimizing the clinical and public health benefit(s) of these agents is of the greatest priority.

Resistance to HIV-1 infection among HIV-exposed seronegative partners in HIV-discordant couples is associated with higher frequency of CD8+ T cells expressing CD107a and b molecules

Methods Ten HIV-1 ESN in HIV-discordant couples were enrolled at the Fann University hospital, Dakar, Senegal. Thirty HIV-1 infected patients (10 HIV-1 non transmitted partners in discordant coupes and 20 HIV-1 infected partners in HIV-concordant couples) and 10 HIV-negative unexposed subjects were included as controls. Levels of CD107a and b, and CD107a/b+IFN-g+ in CD8+ T cells sub-set were measured in fresh PBMC by flow cytometry, in the presence or absence of stimulation with SEB.

Likelihood of Condom Use When Sexually Transmitted Diseases Are Suspected: Results From a Clinic Sample.

To determine the event-level associations between perceived risk of sexually transmitted disease (STD) acquisition/transmission and condom use during penile-vaginal intercourse (PVI) among STD clinic attendees. A convenience sample (N = 622) completed daily electronic assessments. Two questions were proxies of perceived risk: suspicion that the partner might currently have an STD and that "you" might currently have an STD. Participants reported whether condoms were used with PVI events in the past 24 hours. Generalized estimating equations determined the association between each of the perceived risk variables and event-level condom use. For the model pertaining to suspicion of sex partner infection, there were 16,674 events of PVI, with condom use during 10,552 of these events. The effect of current suspicion was significant after adjusting for gender and whether participants identified as African American/Black (estimated odds ratio = 2.17, 95% confidence interval = 1.57-3.00, P = .0001). The model pertaining to suspicion of self-infection included 16,679 events of penile-vaginal sex, with condom use during 10,557 of these events. Again, the effect of current suspicion was significant after adjusting for gender and African American/Black race (estimated odds ratio = 2.05, 95% confidence interval = 1.43-2.40, P = .0001). Tests for interactions with gender and with race were nonsignificant (all Ps > .25). Using an event-level research design, strong associations were found between perceptions of STD risk and condom use in a clinical population. Health care providers and other professionals may indirectly promote condom use by helping clinic patients realistically evaluate their risk of having sex with infected partners or of being a source of STD transmission to others.

Heterosexual risk of HIV transmission per sexual act under combined antiretroviral therapy: systematic review and bayesian modeling.

Although essential for patient counseling and quality of life of human immunodeficiency virus (HIV)-infected individuals, the risk of HIV transmission during 1 unprotected sex act with an HIV-infected person under combination antiretroviral therapy (cART) remains unknown. We reviewed systematically the literature for studies on HIV transmission among heterosexual HIV-serodiscordant couples, where the infected partner was on cART, with regular virological monitoring, reporting on condom use and sexual activity. We used Bayesian statistics to combine data from selected studies, to investigate the per-act risk of HIV transmission through unprotected sex with an HIV-infected person on cART for >6 months. At most, 1 HIV transmission, over an estimated 113 480 sex acts, of which 17% were not condom protected, was reported within 1672 HIV-serodiscordant couples where the index partner had been treated for >6 months. Data were insufficient to determine whether the reported transmission occurred before or after 6 months of cART. We estimated the upper-bound per-act risk of HIV transmission at either 8.7 or 13:100 000, depending on whether the transmission occurred before or after 6 months of cART. These estimates applied whether or not index partners were virally suppressed. Estimating an upper-bound risk <1:100 000 would require observing no HIV transmission while collecting >12 times the available amount of data. Available data do not support zero risk of HIV transmission under cART. The per-act risk of HIV transmission through unprotected sex with HIV-infected individuals on cART in comprehensive care for >6 months (whether or not virally suppressed) is <13:100 000. Estimating a 10-fold lower upper-bound risk may be unfeasible due to high condom use among HIV-serodiscordant couples in most research studies.

Chlamydia Infections in Children and Adolescents

1. Lorena M. Siqueira, MD, MSPH* 1. *Division of Adolescent Medicine, Miami Children’s Hospital, Miami, FL. * Abbreviations: CDC: : Centers for Disease Control and Prevention FDA: : Food and Drug Administration HIV: : human immunodeficiency virus LGV: : lymphogranuloma venereum MIF: : microimmunofluorescent MSM: : men who have sex with men NAAT: : nucleic acid amplification tests PID: : pelvic inflammatory disease STI: : sexually transmitted infection 1. The need for annual screening for chlamydia in sexually active adolescents and young adults is underrecognized because this infection is asymptomatic in most females (75%) and males (50%). 2. Difficulty in diagnosis arises from the range of possible symptoms at presentation of symptomatic infections and the type of testing that can be used in each situation. After completing this article the reader should be able to: 1. Recognize the spectrum of clinical manifestations of chlamydia infection in neonates, children, and adolescents. 2. Discuss the appropriate use of culture and nonculture diagnostic tests for chlamydia infections in various age groups. 3. List the current recommendations for screening and treatment of chlamydia infections. A 17-year-old girl presents with prolonged menstrual bleeding associated with severe menstrual cramping pain. Her menarche was at age 13 years. Subsequent menstrual cycles were monthly, lasting 5 days, with average flow associated with mild to moderate pain relieved by over-the-counter pain medications. The current cycle began a month ago and is associated with severe lower abdominal pain. She admits to sexual activity with one partner and uses condoms intermittently. On examination she is afebrile and in discomfort, with a heart rate of 120 beats per minute. She does not appear anemic and has good capillary refill. She has diffuse abdominal pain with significant tenderness in both the right lower and upper quadrants. Chlamydiae are small obligate, gram-negative, intracellular bacteria that contain both DNA and RNA and were formerly considered to be viruses. There are 3 species that are pathogenic to humans: Chlamydia trachomatis , Chlamydophilia pneumoniae, and Chlamydophilia psittaci . They fall within 2 genera in the family Chlamydiaceae . C trachomatis is in …

Sexual and Reproductive Health and Rights, HIV/AIDS, and Public Health

Since the 1994 International Conference on Population and Development, sexual and reproductive health and rights have received increased attention. Improving sexual and reproductive health is essential in meeting health goals of nations, including the United Nations Millennium Development Goals (MDGs). There has also been a strong emphasis on integrating sexual and reproductive health and HIV information and services. Policy makers, program managers, advocates, and people living with HIV now emphasize sexual and reproductive health– and HIV–related programs and planning. In 2007, a Global Consultation on Sexual and Reproductive Health and Rights of People Living with HIV in Amsterdam focused on research, policy analysis, advocacy, and education, with a better understanding of sexual and reproductive rights of people living with HIV and also creating a supportive health system. Men having sex with men, intravenous drug users, sex workers and their clients are among the most at-risk for contracting HIV. Gender norms related to masculinity, for example homophobia, the subsequent stigmatization and discrimination, compound barriers to health care for people living with HIV who have diverse sexual orientations. Globally, there is a rapid feminization of the HIV and AIDS epidemic due to both sex/biology and unequal gender relations.1 Women, relatively, are at greater risk of acquiring HIV after unprotected sex with infected partners than men because of greater efficiency of male-to-female transmission. Women’s primary risk factor for HIV infection is their inability to control when and whether to be sexually active. Often, gender inequalities underlie such forced and unsafe sex, which has been responsible for a large extent of the HIV epidemic. Female sex workers suffer from a high HIV burden and are one of the core populations for HIV transmission. An estimated 15% of HIV prevalence in the general female adult population is attributable to (unsafe) female sex work.2 Sex workers are highly vulnerable to HIV infection as they often experience forced and unprotected sex. In addition, stigma, discrimination, and poverty further exacerbate sex workers’ vulnerability to HIV. Such activities occur mainly because of the lack of education and economic security. Thus, programs emphasizing male responsibility toward safer sex and condom usage and empowering women with negotiation and life skills training are urgently needed. Easy and affordable access to sexual and reproductive health information and services and access to HIV prevention, treatment, and care is warranted. HIV planning and program need to address the underlying gender inequalities3 and further promote gender equality.

Unreported Antiretroviral Use by HIV-1–Infected Participants Enrolling in a Prospective Research Study

The concentration of viral RNA in plasma is the primary risk factor for sexual transmission of HIV-1 [1–3], and reductions in plasma HIV-1 RNA levels due to antiretroviral therapy (ART) result in marked decreases in HIV-1 transmission risk [4,5]. Results from studies of HIV-1 transmission and disease progression may be more difficult to interpret if a substantial proportion of HIV-1 infected partners have low or undetectable viral loads on ART, and thus, ART use at study enrollment is often an exclusion factor.

Editorial Commentary: Plus ca change ... Antiretroviral Therapy, HIV Prevention, and the HIV Treatment Cascade

Global commitments by 2015 include the Millennium Development Goals, elimination of pediatric human immunodeficiency virus (HIV) infection, and having 15 million persons on antiretroviral therapy (ART); in this context, the major question facing the global AIDS response is how best to use ART for individual health as well as the public health. Recognition of the HIV prevention benefit of ART has stimulated calls for earlier and more widespread ART globally, with the 96% efficacy in reducing sexual transmission demonstrated in the landmark HIV Prevention Trials Network (HPTN) 052 [1] study often quoted. Earlier in 2013, the World Health Organization (WHO) issued consolidated ART guidelines that recommend initiation of ART at a CD4 count of ≤500 cells/μL [2], and many expect global guidelines to eventually recommend ART for all persons living with HIV, irrespective of the absence of data from randomized clinical trials [3]. There is more to HIV treatment than guidelines, however, and in the current issue of Clinical Infectious Diseases, McNairy and El-Sadr [4] usefully discuss the health-systems challenges inherent to the “HIV treatment cascade.” This term refers to the sequential steps that take individuals from HIV diagnosis through enrollment into care, timely initiation of ART, adherence to treatment, and viral suppression. An intact cascade is essential if the benefits of ART are not to be squandered and more HIV-infected persons are to be safely placed on therapy. The HIV treatment cascade is not a new concept but uses earlier modeling applied to tuberculosis and sexually transmitted infections, referred to, respectively, as the Piot and Piot-Fransen models [5, 6]. For these conditions, the multiple steps required for medical success are at risk from constant leakage. Dropout can occur at numerous points so that the final number of beneficial outcomes may be small compared to the number of people entering the cascade. Such observations apply to medical care more broadly and explain the relatively poor impact from interventions for many chronic diseases such as hypertension when analyzed at the population level. In comparison, once-only interventions with sustained benefit such as male circumcision for HIV prevention can have greater population-level impact despite imperfect efficacy. The central role that ART plays in today’s HIV prevention response has roots early in the pandemic. Analytic epidemiologic studies showed that viral load was associated with risk of transmission for all transmission modes. Zidovudine monotherapy reduced transmission from the infected partner in discordant couples in the late 1980s [7], as well as from mothers to infants in the landmark AIDS Clinical Trials Group (ACTG) 076 study [8]. Public health officials raised the possibility of ART and viral load suppression playing a role in reducing HIV transmission at a population level more than a decade ago [9]. The enormous interest today in HIV treatment as prevention and the impetus to implement it result from different but allied forces: the early observations cited above; mathematical modeling showing that ART implemented on a wide scale could substantially reduce and potentially control generalized HIV epidemics [10]; programmatic experience confirming reduced HIV transmission at a population level with ART scale-up [11, 12]; the results of the HPTN 052 study [1]; and the general belief that earlier treatment would be beneficial for individual health. The single most important indicator that HIV treatment and public health programs should be concerned about today is viral load, which is key to both transmission and disease progression. Monitoring and evaluation efforts strive to capture indicators that describe how well viral load is being suppressed across the population, either through depictions of the cascade or summary estimates such as community Received and accepted 7 January 2014. Correspondence: Kevin M. De Cock, MD, Centers for Disease Control and Prevention Kenya, Unit 8900, Box 360, DPO AE 09831-0360 (kdecock@ke.cdc.gov). Clinical Infectious Diseases Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. Thiswork iswritten by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/cid/ciu026

Knowledge, Attitude and Practice towards Condom Utilization among Patients Enrolled on Antiretroviral Therapy: Case of Mokoni Health Centre, Northern Ethiopia

The burden of HIV/AIDS high in sub-Saharan countries which constitutes two third of globe and is worst in Ethiopia. Therefore identifying determinants of consistent condom use in HIV patients who are on ART had paramount importance in the prevention and control of the diseases. A little is known about the practice of condom use among HIV positive patients. The aimed of this study was to assess knowledge, attitude and practice towards condom utilization among people living with HIV/AIDS enrolled on ART in Mokoni town. An institutional based cross sectional study was conducted among ART users in Mokoni health center from June-august 2013. Data on the study variables was gathered using semi-structured questionnaire. After the subject was asked for their volunteer participation, then we collected data using interview. Descriptive statistics was used to determine the frequency and percentage of different variables. Data was presented in the form of tables and graphs. From the total study participants 177(56.73%) were females. Among 312 participants 35(11.22%) of them had knowledge about people on ARV can’t transmit the HIV virus to un infected partners ,277(88.73%) knew even people taking ARV can transmit HIV to un infected partner .From the total 312 respondents 136(43.59%) had attitudes about people on ARV tend to engage in risky sexual practice ,176(56.41%) didn’t believe people on ARV tend to engage in risky sexual practice. among the total respondents 121(38.78%) agreed that because of availability of ARV people could again engage in un protected sex, 64(20.51) agreed that it was safe to engage in unprotected sex with a person taking ARV. From 165 who were currently use Patterns of condom use among 165 who are using condom currently and 116(70.30%) were consistently used a condom. The majority of patients ART enrolled always use a condom during sexual intercourse. Significant numbers of the respondents were well confident about using condoms and attended session demonstrating about using condoms. Free and explicit discussion on safe sex and enhanced positive attitudes toward condom use should be encouraged.

Chlamydia and Gonorrhea Diagnosis, Treatment, Personnel Cost Savings, and Service Delivery Improvements After the Implementation of Express Sexually Transmitted Disease Testing in Maricopa County, Arizona

The demand for low-cost sexually transmitted disease (STD) services in Maricopa County (Phoenix area) is high. Improved methods for STD/HIV testing are needed to increase the number of patients receiving testing. The present study sought to evaluate an STD/HIV express testing (ET) option for patients identified as being at lower risk for infection. Clients reporting current STD symptoms, contact to an infected partner, or health department referral were identified via questionnaire and routed to a traditional provider visit (PV); those not reporting these situations were routed to ET (laboratory-only). Demographics, treatment completion, and treatment intervals were compared among patients diagnosed as having chlamydia and gonorrhea through ET and PV encounters in September 2008 to July 2011. Personnel costs were compared for each of the 2 visit types. The number of clinic turn-aways for the 2-month time interval before the start of the program was compared with the 2-month interval at the end of the evaluation. Of the 36,946 clients seen at Maricopa County Department of Public Health, 7466 (20.2%) were patients seen through express visits. Overall chlamydia and gonorrhea positivity was lower among ET patients (527/7466; 7.1%) as compared with those tested through PVs (6323/29,480; 21.4%). Treatment completion rates were comparable but were higher among patients seen through PVs (99%) as compared with ET (94%). A savings of $2936 per 1000 patients seen was achieved when 20% of clients were routed through ET. Clinic turn-aways decreased significantly, from 159 clients during the 2 months before implementation of ET to 6 patients during the last 2 months of evaluation (96% reduction). This ET system included an effective patient routing process that provided an efficient way to increase access to STD testing among persons at lower risk, at a reduced cost per patient, while maintaining high treatment coverage.

AIDS: The Final Chapter?

AIDS: The Final Chapter?

Assessing the Cost Effectiveness of Pre-Exposure Prophylaxis for HIV Prevention in the US

About 50,000 people are infected with HIV in the US each year and this number has remained virtually the same for the past decade. Yet, in the last few years, evidence from several multinational randomized clinical trials has shown that the provision of antiretroviral drug to uninfected persons (i.e. pre-exposure prophylaxis) reduces the incidence of HIV by about 50%. However, evidence from cost-effectiveness studies conducted in the US yield widely varying estimates of the cost per quality-adjusted life-year (QALY) gained, and this variation reflects the substantial uncertainty surrounding the determinants of HIV transmission (e.g. adherence rates to prophylactic medications, the average number of sexual partners, the number and types of sexual acts, the viral load of infected partners, and the proportion of contacts where condoms are used), as well as different approaches to translating a reduction in HIV cases into an estimate of the increase in the number of QALYs.

Toward Enhancing Sexually Transmitted Infection Clinic Efficiency in an Era of Molecular Diagnostics

In an era of constrained resources, new molecular techniques may make it possible to detect common sexually transmitted infections (STIs) without physical examination in selected groups of men. Our objectives were to define the contribution of the physical examination in detecting clinically meaningful diagnoses that may not be identified by current laboratory methods and to identify characteristics that can stratify men into the appropriate risk category. A retrospective study from a database of all male visits to 2 urban STI clinics in Baltimore between 1990 and 2001 was conducted. Men were stratified on the basis of reason for visit. Proportions for diagnoses that would have been missed without physical examination were compared using the χ2 test. Logistic regression was used to assess which factors were most predictive of missed diagnoses. A total of 58,073 of 140,052 records were included: 29,172 were asymptomatic, 23,972 were symptomatic, and 4929 were asymptomatic contacts of an infected partner. In addition, 2.7% of ASYM, 10.4% of symptomatic, and 4.5% of contact patients would have had missed diagnoses if no physical examination had been performed. For symptomatic patients, if those reporting rash, lesion, or genital itch were examined, the percent with missed diagnoses would drop to 3.7%. Asymptomatic men may be candidates for accelerated STI testing, which includes the submission of genital and extragenital swabs as well as blood samples for HIV and syphilis testing without a physical examination. A significant proportion of symptomatic men would miss the opportunity for same-day treatment of gonococcal or nongonococcal urethritis.

Antiretroviral Therapy for Prevention of HIV Transmission in HIV-Discordant Couples

CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infection.

There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992-2013--all phase II and phase III safety and effectiveness studies--testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important.

HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study

In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART). We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index) initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.

Individual and partner risk factors associated with abnormal cervical cytology among women in HIV-discordant relationships

Individual and sexual partner characteristics may increase the risk of abnormal cervical cytology among women in human immunodeficiency virus (HIV)-discordant relationships. Papanicolaou smears were obtained in a prospective cohort of Kenyan HIV-discordant couples. Of 441 women, 283 (64%) were HIV-infected and 158 (36%) were HIV-uninfected with HIV-infected partners. Overall, 79 (18%) had low-grade and 25 (6%) high-grade cervical abnormalities. Male herpes simplex virus type 2 (HSV-2) seropositivity and lower couple socioeconomic status were associated with cervical abnormalities (p < 0.05). HIV-uninfected women with HIV-infected male sex partners (CD4 > 350 cells/µL) had the lowest prevalence of high-grade cervical lesions. HIV-infected women (CD4 > 350 cells/µL) and HIV-uninfected women with HIV-infected partners (CD4 ≤ 350 cells/µL) were at similar intermediate risk (p > 0.05), and HIV-infected women (CD4 ≤ 350 cells/µL) had significantly higher risk of high-grade cervical abnormalities (p = 0.05). Women in HIV-discordant relationships have high rates of cervical lesions and this may be influenced by couple-level factors, including HIV status and CD4 count of the infected partner.