The authors present maternal and child outcomes 24 months after a randomized clinical trial comparing triple nucleoside reverse transcriptase inhibitor (NRTI), protease inhibitor (PI), and standard care with nevirapine among 730 HIV-positive pregnant women on highly-active antiretroviral therapy (HAART) for the prevention of mother-to-child transmission (PMTCT) in Botswana. Low mother-to-child transmission (MTCT) was maintained with no additional MTCT after six months. All but one of 14 maternal deaths occurred after stopping HAART. Thirty-seven child deaths occurred, and mortality was highest within three months of weaning from breastfeeding (22 deaths). In the trial, 285 women were randomized to the NRTI arm, 275 to the PI arm, and 170 to the observational arm (CD4 count<200 received standard-of-care treatment). The child death rate within three months of weaning was 7.9 per 100 person-years, compared to 2.1 during breastfeeding, but declined to 1.1 after three months; no significant differences in child survival between the arms were found. The greatest overall increase in CD4 count occurred in the PI arm. These results support the efficacy of HAART for PMTCT. Because survival benefits following HAART for women was not evident, the findings support the World Health Organization recommendation of lifelong ART at a higher CD4 count. The authors called for more research to determine whether HAART promotes child survival and if biomedical interventions can reduce mortality risk post-breastfeeding.
AIDSFree Prevention Update: August 2013 Edition
Shapiro, R.L., Kitch, D., Ogwu, A., et al. AIDS (July 2013), Vol. 27 No. 12, pp. 1911-1920.
Friend, D.R., and Kiser, P.F. Antiviral Research (2013), Vol. 99, pp. 391-400.
The authors discussed the development of microbicides, requirements for efficacy, and challenges. The Centre for the AIDS Programme of Research in South Africa (CAPRISA)-004 trials provided modest evidence that microbicides can be effective in preventing HIV transmission, with optimal adherence increasing effectiveness. Understanding of microbicides has increased over the past decade, yet adherence, funding, clinical trial design, and testing remain challenging. In early research, trials of non-specific HIV inhibitors, e.g., surfactants were stopped due to futility, increased HIV risk, or adverse events. Low adherence also contributed to findings of ineffectiveness in the few trials of antiretroviral (ARV) drugs, tenofovir (TFV) and dapivirine (DPV). Through 2014, the Follow-on African Consortium for Tenofovir Studies (FACTS) 001 study will enroll 2,900 women in South Africa to test end-point safety and effectiveness of the same dosing regimen of Tenofovir (1 percent) as CAPRISA-004. Long-acting microbicides and multipurpose prevention technologies (MPTs), which address two or more reproductive or sexual health needs, are in development. MPTs may expand benefits and improve adherence, as is hoped of intravaginal rings (IVRs), which are generally accepted by women. Moving towards MPTs that combine ARVs for HIV prevention and contraception are needed at this stage. Planned trials are assessing the efficacy of various IVR formats. Lessons learned from previous developments, including failures rooted in behaviors and products must be built into future trials. Innovative technologies and improved dosage regiments could improve acceptance of and adherence to microbicides.
Rausch, D.M., Grossman, C.I., and Erbelding, E.J. Journal of Acquired Immune Deficiency Syndromes (June 2013), Vol. 63 No. 1, pp. S6-S11.
The authors presented efficacy challenges experienced in recent antiretroviral therapy (ART) prevention trials; discussed behavioral challenges to ART and their effects on the design and implementation of prevention trials; and outlined priorities for future research within combination HIV prevention. A multidisciplinary approach that includes current behavioral science is essential to maximizing and sustaining the benefits of ART-based and integrated combination prevention. Clinical trials of both oral and topical approaches for pre-exposure prophylaxis have yielded both promising findings and failure, even when the same product and dose was tested. In several of these tests, adherence was a critical factor. The HIV Prevention Trials Network (HTPN)-052, which incorporated a counseling intervention, was highly successful in preventing HIV transmission among serodiscordant couples. The authors stated that because trials of biomedical approaches to HIV prevention yield conflicting results, sociobehavioral factors that may affect trial outcomes should be examined. Behavioral theories or models have influenced HIV prevention interventions, but cannot in themselves effectively address the HIV epidemic. Theoretical behavior models must evolve to complement and advance combination HIV prevention efforts—including in intervention design and potential behavioral impacts on the outcomes of clinical trials—and assessment of behavioral outcomes must be improved. Integrating behavioral and biomedical approaches is critical if global HIV prevention is to achieve maximum impacts.
Hoffman, I.F., Latkin, C.A., Kukhareva, P.V., et al. AIDS and Behavior (September 2013), Vol. 17 No. 7, pp. 2510-2520.
In Russia, people who inject drugs (PWID) typically interact within small networks that may influence the HIV epidemic. The authors described the results of a randomized controlled trial assessing the effectiveness of a peer-educator intervention for PWID and their network members in St. Petersburg, aimed at reducing HIV incidence and risk behaviors. The findings indicated that peer-education interventions may reduce HIV incidence within marginalized PWID networks and should be included in a comprehensive HIV prevention approach. From December 2004 to November 2007, index participants were recruited and encouraged to identify network participant(s). In total, 432 participants enrolled and were randomized to the intervention or control. Intervention index participants attended eight training sessions on the risks of injecting drug use, sexual risk behavior, and risk reduction and communication skills. Control index participants attended sessions on social development skills and lifestyle discussions. Of 240 HIV-negative participants (at baseline), 160 participants received follow-up visit(s). At follow-up, estimated HIV incidences were 7.8 and 19.6 in the intervention and control groups, respectively. Analysis comparing HIV incidence between the groups using parametric, semi-parametric, and non-parametric estimates had similar results, showing that incidence in the control group was approximately two times greater. Future research may benefit from measuring a community effect instead of individual HIV incidence.
McNairy, M.L., Deryabina, A., Hoos, D., et al. Drug and Alcohol Dependence (July 2013), E-publication ahead of print.
The authors reviewed HIV services available for people who inject drugs (PWID) in Central Asian countries and discussed concerns about research on and implementation of antiretroviral therapy (ART) for prevention in this group. Overall, ART for HIV prevention among PWID in this region must be coordinated with current HIV services, ensuring that those who are HIV-positive have access to ART for treatment. HIV incidence continues to rise in Central Asia, particularly among PWID. Injection drug use accounts for nearly 63 percent, 57 percent, and 50 percent of HIV infections in Kazakhstan, Kyrgyzstan, and Tajikistan, respectively, and a high proportion of PWID engage in risky sexual behaviors. Stigma, marginalization, and restrictive policies prevent PWID from accessing HIV prevention services or drug-related treatment; creating gaps in the cascade of HIV care, including HIV testing and linkage to care and treatment. Poor adherence to ART may stem from discrimination or lack of support and counseling from trained providers to address issues for PWID. Risk-reduction strategies, such as pre-exposure prophylaxis and opioid substitution therapy, should be evaluated within a combination approach. The gaps in the HIV continuum must be addressed in a comprehensive strategy, combined with research on feasibility and interventions to increase demand for HIV testing and to strengthen retention and adherence.
Des Jarlais, D.C., Pinkerton, S., Hagan, H., et al. Advances in Preventative Medicine (June 2013), Vol. 2013.
The authors reviewed the history of and lessons learned from the past three decades in HIV prevention for people who inject drugs (PWID) and discussed critical issues for future research and public health programs. Despite successes in HIV prevention among PWID, including large-scale syringe access programs, combination prevention, and integrated health and social approaches (primarily in high-income countries), lack of resources and political will, stigmatization, and other factors, hinder effective HIV prevention for PWID in resource-limited countries. Long-term data for HIV prevention among PWID are inadequate because of stigmatization, friction between law enforcement and drug users, and political leaders’ belief that drug use is a “Western issue.” The authors described two modeling studies which indicated that combination programs would dramatically reduce HIV incidence among PWID in two countries. Current economic pressures point toward reducing programming for PWID, particularly in low-prevalence epidemics; the authors argued against scaling these programs down because other factors, e.g., sexual transmission, could increase HIV. Lastly, the authors described two opposing policy perspectives to injecting drug use: the proscriptive “war on drugs” and the pragmatic “harm reduction” approach, which focuses on public health and human rights. The authors concluded that the successes in HIV prevention among PWID have informed global goals for improving overall health (including HIV prevention and care) through a rights-based, politically supportive environment.
Wagner, K.D., Pitpitan, E.V., Chavarin, C.V., et al. Sexually Transmitted Diseases (August 2013), Vol. 40 No. 8, pp. 619-623.
The authors conducted a cross-sectional study (from June 2011-August 2012) in Tijuana, Mexico to assess the extent to which 170 drug-using male clients of female sex workers (FSWs) have also been paid for sex; to estimate the prevalence of sexual partner types; and to understand the association between sexual partner type and HIV risk. Overall, 45 (26.5 percent) of male clients reported having any paying sexual partners in the previous four months, with 11 (24 percent) reporting both male and female partners. This suggests that drug-using male clients and male sex workers may overlap within a group who both pay and are paid for sex. Having a paying partner was significantly associated with an increased probability of being positive for HIV or another sexually transmitted infection—HIV-positive persons were 3.5 times more likely to report this behavior. Injection drug and cocaine use in the previous four months was also independently associated with reporting paying sexual partners. Further research should explore behavioral characteristics, including injecting drug and cocaine use and condom use practices with varying partner types, among this group. The authors concluded that HIV prevention activities for drug-using male clients should aim to increase the availability and correct use of condoms in sex work venues.
Kacker, S., Frick, K.D., Quinn, T.C., et al. Sexually Transmitted Diseases (July 2013), Vol. 40 No. 7, pp. 559-568.
The authors modeled the short- and long-term financial implications of the scale-up of male circumcision (MC), taking into account infections shown to be averted by MC. They simulated four strategies with various rates and extents of MC scale-up, and compared the results with a baseline scenario of current MC prevalence and trends in Rakai District, Uganda. The strategies included a combination of gradual and rapid scale-up with either adolescents/adults (aged 15-49) only or including infants (aged 0-1). Cost savings from MC-related reduction in infections varied from US $197,531 after five years of scale-up focused on adolescents/adults, to US $13.7 million after 25 years with infant circumcision included. Including infants in MC strategies is more costly in the short term but achieves considerable savings long-term. Also, rapid scale-up of MC may lead to greater savings earlier, and over time, compared to gradual strategies, due to averted infections. Reduced HIV incidence accounted for approximately 46 percent of reductions in infection-related costs and 50 percent of cost savings; 79 percent of costs in five years; and 90 percent of cost savings in 25 years. The authors concluded that investment in MC strategies that incorporate both infants and adolescents/adults may have greater long-term impact than targeting the latter population only. The findings support health and economic benefits of MC scale-up.
Rosenberg, N.E., Westreich, D., Bärnighausen, T. AIDS (July 2013), E-publication ahead of print.
The authors conducted a cohort study from 2006 to 2011 among youth (ages 15-24) in high-prevalence KwaZulu-Natal, South Africa, using household surveillance and HIV and health surveys to compare HIV acquisition among youth who had and had not been exposed to HIV testing and counseling (HTC). Analysis suggested that HTC is effective in reducing HIV acquisition among uninfected youth; specifically, after HTC, there was a 41 percent reduction in the hazard of HIV acquisition over 4.5 years. While longitudinal multivariate analysis of risk factors showed that HTC was associated with lower incidence, in the short term, HTC-exposed youth were at greater risk. Of 3,959 youth eligible, 29 percent and 71 percent were initially HTC-exposed and-unexposed, respectively. HTC-exposed youth were more likely to be female, sexually experienced, and previously pregnant. Of those unexposed, 1,064 (38 percent) became HTC-exposed during follow-up. Initially, approximately one-third of respondents reported experiencing sexual debut and 43 percent of sexually active youth reported using a condom during their last sexual intercourse. Future research should examine the effect of HTC on sexual behaviors. Scaling up access to youth-friendly HTC, particularly as part of a combination prevention approach, and ensuring linkages to appropriate treatment and care could have substantial public health effects. The authors also concluded that these findings support South Africa’s recent action to provide HTC in secondary schools.
McGrath, N., Eaton, J.W., Bärnighausen, T.W., et al. AIDS (July 2013). E-publication ahead of print.
Using annual surveillance data in KwaZulu-Natal, South Africa, the authors analyzed population-level trends in reported sexual behavior among men (aged 17-54) and women (aged 17-49) during the rollout of antiretroviral therapy (ART) from 2005 to 2011. They found no evidence of increased risky sexual behavior during this period. Further, after adjusting for missing data, trends indicated some evidence of reductions in reported risky sexual behaviors, e.g., reported reductions in the number of multiple and concurrent sexual partnerships. Knowledge of HIV status increased, especially among women. Condom use at last sex with a regular partner increased significantly (by nearly 3 percentage points and 4 percentage points per year among men and women, respectively); the average proportion of men and women reporting this behavior in 2005 (26 percent) increased to an average of 49 percent in 2011. Condom use at last sex with casual partners did not increase significantly, but condom use with these partners was already relatively high. Condom use was highest at younger ages and lowest among married persons. There are still opportunities to promote HIV testing and counseling and informed use of condoms. The authors concluded that continued monitoring of population-level sexual behavior is needed to further assess the effectiveness of combination prevention programs and the long-term impact of ART on risky sexual behavior.
Dunkle, K.L., Jewkes, R.K., Murdock, D.W., et al. PLOS Medicine (June 2013), Vol. 10 No. 6.
The authors conducted a cross-sectional household survey with 1,705 adult men in the Eastern Cape and KwaZulu-Natal, South Africa in 2008 to assess the prevalence of men who have sex with men (MSM) in consensual relationships, male-on-male sexual violence and victimization, and sociodemographic factors and HIV prevalence associated with these behaviors. One in twenty men, or 5.4 percent, reported having consensual sexual activity with another man; of these, 48 percent reported having had oral or anal sex with another man. MSM behavior was reported more frequently by men in lower socioeconomic households. Nearly all men also reported having sex with women. Further, 1 in 10 reported male-on-male sexual violence, including oral or anal rape (3.3 percent), and perpetration of this behavior (2.9 percent). MSM with a history of consensual sex with men were seven times more likely to experience sexual violence from another man, and three times more likely to perpetrate this sexual violence against another man, compared to those who did not. Among 1,220 men who consented to an HIV test, prevalence was higher among men with a history of consenting to sex with a man and among perpetrators of male sexual violence. Research is needed on the overlap between male-male and heterosexual behaviors, and on male-on-male sexual violence, and the implications for HIV risk and prevention strategies.
Geibel, S. Journal of the International AIDS Society (2013), Vol. 16.
Geibel reviewed evidence on lubricants in terms of their effects on and compatibility with condoms and their biological safety. The author also discussed documentation of lubricant use and relevance to current guidance for HIV prevention in Africa. While improving, evidence on the safety of and compatibility between lubricants and condoms is not well documented, and criteria for lubricant safety and procurement are needed. Water-based lubricants remain expensive in sub-Saharan Africa, and their potential HIV risks are insufficiently documented. Because of the scarcity and high cost of water-based lubricants, the author explained that many Africans use numerous lubricants, including household or oil-based products of unknown safety. Safety regulations on lubricants, particularly products not marketed for sexual use, may not be rigorous. Current guidance does not indicate preferred lubricants or clarify the safety of lubricants, but some guidelines from international organizations advise avoiding oil-based products and list products that damage latex. Organizations such as the International Rectal Microbicides Advocates monitor research to provide guidance on lubricant safety and to advocate for continued research. Population-based surveys in Africa, not only with key populations, should further evaluate lubricant use, type, and accessibility. Further research and guidance from the Food and Drug Administration are needed to address safety and ensure that public health professionals market lubricants that do not increase HIV risk.
Sgaier, S.K., Ramakrishnan, A., Dhingra, N., et al. Health Affairs (2013), Vol. 32 No. 7, pp. 1265-1273.
The authors discussed the process, results, and lessons learned from the transfer of a large-scale HIV prevention program in India—Avahan—from its donor and original implementer, the Bill and Melinda Gates Foundation (henceforth the Gates Foundation), to the Government of India and beneficiary stakeholders between 2005 and 2013. Aligning with government HIV programs and structure, transferring skills and capacity to the government, and improving managerial skills were critical to making the transition and sustaining program outputs. The Gates Foundation invested U.S. $100 million (28 percent of program funds) to activities to secure the project's sustainability, and in the project's second five-year period (2009-2013) included specific goals for transition, focusing on partnership with the government. The Indian Government increased its HIV budget by 400 percent during the transition, with an increased focus on prevention. Lessons learned included that Government leadership and political commitment were essential to sustaining program outputs. Further, transition requires early planning; it is a “front-loaded” process in which most of the work occurs before the transition, and transition is a fluid process, requiring phased implementation to accommodate adjustments. Challenges included staff turnover and development of effective strategies to minimize declines in program performance and quality during the process. An initial analysis indicated overall sustained program outputs following the transition, but the authors noted that long-term follow-up will be necessary.
Vermund, S.H., Tique, J.A., Cassell, H.M., et al. Journal of Acquired Immune Deficiency Syndromes (June 2013). Vol. 63 Suppl. 1, pp. S12-S25.
The authors discussed biomedical HIV prevention strategies in terms of their effectiveness and the complexities of translating them into real-world settings. The authors asserted that a combination HIV prevention approach that includes proven biomedical technologies will likely have the greatest impact in reducing HIV, but questions remain on how these technologies function on broad scales. For example, evidence on such technologies as treatment as prevention (TasP) and prevention of mother-to-child transmission (PMTCT) shows strong impacts. However, the effectiveness of interventions highly depends on behavioral and structural factors. Current studies are still assessing the population-level effect of TasP, while numerous barriers to universal PMTCT coverage limit the full benefits of this approach. Pre-exposure prophylaxis (PrEP) has shown promise in several trials, but effectiveness has varied between oral and topical modalities and between men and women. Meanwhile, evidence on the effectiveness of post-exposure prophylaxis (PEP) is positive but has not been tested in controlled trials. While other biomedical prevention interventions, including medical male circumcision, harm reduction strategies for people who inject drugs, and condom use can be effective in reducing HIV risk, inconsistent implementation, and social, behavioral, and structural barriers may impede effectiveness. The authors concluded that biomedical strategies need to be adapted to each context, and can be applied as part of a combination approach that includes behavioral and structural strategies.
Beyrer, C., Sullivan, P., Sanchez, J., et al. AIDS (August 2013). E-publication ahead of print.
The authors examined recent evidence and comprehensive reviews on the global HIV epidemic, focusing on the high HIV burden among MSM. Comprehensive, evidence-based HIV services and programs are critically needed for MSM— especially for young MSM—and during key stages in the transmission cycle. Available data indicate that HIV incidence rates are high, especially among young MSM, in which stigma, discrimination, and criminalization limit the availability, uptake, and effectiveness of current HIV prevention and treatment services. HIV may spread rapidly among MSM networks because of the ease of transmission through receptive anal intercourse and because of the infectiousness of recently-infected men. Rapid transmission and limited service-seeking among young MSM may explain the minimal impact of treatment as prevention in this sub-population. Individual behaviors are compounded by social factors, such as stigma, highlighting the importance of continued activism. Further, black MSM are disproportionately affected in many countries. Several factors, e.g., differences in social networks and clinical outcomes, may contribute to this greater impact; nevertheless, this sub-population is more likely to have undiagnosed HIV, limited or unused access to HIV services, and lower incomes. The ongoing development of promising prevention technologies, e.g., rectal microbicides, may reduce the spread of HIV among MSM. Existing minimum requirements for programs targeting MSM, while essential, may be insufficient to control HIV among MSM. The authors suggest that integrated and combination prevention interventions will be necessary to reverse expanding HIV incidence among MSM.