Articles tagged as "Blood / body fluids and HIV prevention"

Self-report and pill count: unreliable measures of adherence in HIV prevention trials

Accuracy of self-report and pill-count measures of adherence in the FEM-PrEP clinical trial: implications for future HIV-prevention trials.

Agot K, Taylor D, Corneli AL, Wang M, Ambia J, Kashuba AD, Parker C, Lemons A, Malahleha M, Lombaard J, Van Damme L. AIDS Behav. 2015 May;19(5):743-51. doi: 10.1007/s10461-014-0859-z.

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing ≤1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p < 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed.

Abstract  Full-text [free] access

Editor’s notes: A number of studies have demonstrated that pre-exposure prophylaxis (PrEP) is effective in reducing HIV transmission when adherence is high. Understanding factors affecting adherence, and evaluating methods to best measure adherence are therefore of crucial importance. Despite excellent self-reported adherence, the FEM-PrEP and VOICE trials did not illustrate a benefit of PrEP. In this study, drug concentrations were assessed in 1200 visits from 150 FEM-PrEP trial participants to determine adherence. These results were used to assess the accuracy of three measures of self-reported adherence and also pill counting. All four measures had poor positive predictive value, ranging from 26.2% to 42.4%. There was an increase in misreporting of adherence over time which may be associated with lower adherence levels over time. In semi-structured interviews, most participants said that they did not misreport adherence. The authors call for improvements in methods to reduce socially desirable responses through participant self-report, and examination of the reasons why people join HIV prevention trials. Future trials may also need to consider using drug concentrations in addition to currently used methods to better estimate adherence.

Africa
Kenya, South Africa
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Early postnatal cytomegalovirus infection may predict subsequent HIV transmission through breastfeeding

Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers.

Chang TS, Wiener J, Dollard SC, Amin MM, Ellington S, Chasela C, Kayira D, Tegha G, Kamwendo D, Jamieson DJ, van der Horst C, Kourtis AP; BAN Study Team. AIDS. 2015 Apr 24;29(7):831-6. doi: 10.1097/QAD.0000000000000617

Background: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown.

Methods: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition.

Results: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05).

Conclusion: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV.

Abstract access 

Editor’s notes: Studies have illustrated that mother-to-child HIV transmission is more frequent among neonates with congenital cytomegalovirus (CMV) infection. Infants co-infected with HIV and CMV have higher rates of HIV disease progression and death. This study using data and samples of infant plasma and peripheral blood mononuclear cells are from the Breastfeeding, Antiretrovirals and Nutrition (BAN) randomised, controlled clinical trial (RCT). The study examines whether postnatal CMV infection in the infant is associated with HIV transmission through breastfeeding. The study investigates the relationship between postnatal antiretroviral therapy and postnatal CMV acquisition. The data suggests that early postnatal CMV infection in an HIV-exposed uninfected infant may predict subsequent HIV transmission through breastfeeding and infant mortality. The study confirmed previous findings that approximately 70% of breastfed infants born to mothers living with HIV in low-income settings acquire CMV infection by six months of age. However, the study did not find an association between maternal antiretroviral therapy and the risk of postnatal CMV transmission. It is important to note that in the RCT, antiretroviral therapy was only initiated at the onset of labour.  The effect of maternal antiretroviral therapy taken earlier in pregnancy on the prevention or delay of CMV acquisition remains unknown, although a few observational studies have found that maternal antiretroviral therapy reduces congenital and early postnatal CMV infection. It is biologically plausible that antiretroviral therapy reduces or prevents CMV reactivation in the mother, thus preventing transient episodes of maternal CMV viraemia. This mechanism could explain reduced CMV transmission to the infant (be that before or after birth). HIV-exposed but uninfected infants experience higher morbidity and mortality; any such disease attributable to CMV could therefore potentially be reduced by initiation of antiretroviral therapy earlier in pregnancy.

Africa
Malawi
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Transient increase in HIV shedding from male circumcision wounds

HIV shedding from male circumcision wounds in HIV-infected men: a prospective cohort study.

Tobian AA, Kigozi G, Manucci J, Grabowski MK, Serwadda D, Musoke R, Redd AD, Nalugoda F, Reynolds SJ, Kighoma N, Laeyendecker O, Lessler J, Gray RH, Quinn TC, Wawer MJ, Rakai Health Sciences P. PLoS Med. 2015 Apr 28;12(4):e1001820. doi: 10.1371/journal.pmed.1001820. eCollection 2015.

Background: A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC.

Methods and findings: HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50 000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment.

Conclusion: Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.

Abstract  Full-text [free] access

Editor’s notes: Voluntary medical male circumcision (VMMC) decreases the heterosexual acquisition of HIV, herpes simplex virus type 2 and human papillomavirus (HPV) in men. There are also benefits for female partners. Among men living with HIV, VMMC reduces genital ulcer disease and HPV, but it does not reduce the risk of HPV transmission. Further, VMMC increases HIV transmission to female partners among people who engage in sex before wound healing, though not among couples who delay resumption of sex. Men living with HIV may seek VMMC for multiple reasons, and WHO guidelines state that they should not be denied the service if they request it. Despite counselling to abstain from sex until full wound healing, a substantial proportion of men resume sex before this. In this cohort study among HIV-positive men in Uganda, the authors found that penile HIV shedding had a transient increase after VMMC, peaking in the second week after VMMC. By 6 to 12 weeks after surgery, when wounds had healed, HIV shedding was lower than pre-surgery. There was no change in plasma viral load during the study. Among men with HIV shedding, the lowest quantities of shedding were observed among men on ART and with undetectable viral load. The authors highlight the potential role of ART to reduce the risk of HIV transmission following VMMC, for example by considering initiating ART prior to VMMC for men living with HIV, and encouraging adherence to suppress viral load.  With current WHO guidelines, the majority of men living with HIV attending for VMMC will be eligible for ART, and VMMC could be a useful entry point for treatment although this may pose logistical challenges.

Africa
Uganda
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Multiple harms faced by Azerbaijani prisoners

Burden of substance use disorders, mental illness, and correlates of infectious diseases among soon-to-be released prisoners in Azerbaijan.

Azbel L, Wickersham JA, Wegman MP, Polonsky M, Suleymanov M, Ismayilov R, Dvoryak S, Rotberga S, Altice FL. Drug Alcohol Depend. 2015 Mar 19. pii: S0376-8716(15)00136-2. doi: 10.1016/j.drugalcdep.2015.02.034. [Epub ahead of print]

Background: Despite low HIV prevalence in the South Caucasus region, transmission is volatile. Little data are available from this region about addiction and infectious diseases among prisoners who transition back to communities.

Methods: A nation-wide randomly sampled biobehavioral health survey was conducted in 13 non-specialty Azerbaijani prisons among soon-to-be-released prisoners. After informed consent, participants underwent standardized health assessment surveys and testing for HIV, hepatitis B and C, and syphilis.

Results: Of the 510 participants (mean age=38.2 years), 11.4% were female, and 31.9% reported pre-incarceration drug injection, primarily of heroin. Prevalence of HCV (38.2%), HIV (3.7%), syphilis (3.7%), and HBV (2.7%) was high. Among the 19 HIV-infected inmates, 14 (73.7%) were aware of their HIV status, 12 (63.2%) were receiving antiretroviral therapy (ART), and 5 (26.3%) had CD4<350cells/mL (4 of these were on ART). While drug injection was the most significant independent correlate of HCV (AOR=12.9; p=0.001) and a significant correlate of HIV (AOR=8.2; p=0.001), both unprotected sex (AOR=3.31; p=0.049) and working in Russia/Ukraine (AOR=4.58; p=0.008) were also correlated with HIV.

Conclusion: HIV and HCV epidemics are concentrated among people who inject drugs (PWIDs) in Azerbaijan, and magnified among prisoners. A transitioning HIV epidemic is emerging from migration from high endemic countries and heterosexual risk. The high diagnostic rate and ART coverage among Azerbaijani prisoners provides new evidence that HIV treatment as prevention in former Soviet Union (FSU) countries is attainable, and provides new insights for HCV diagnosis and treatment as new medications become available. Within prison evidence-based addiction treatments with linkage to community care are urgently needed.

Abstract access 

Editor’s notes: This is an important study describing prevalence of HIV, hepatitis B and hepatitis C among a prison population in Azerbaijan. The importance of the study stems from the need to monitor infections among a highly vulnerable population of prisoners. While the study does not report on current injecting drug use among the population, a third of the sample reported injecting drugs prior to their detention and will need support with their injecting drug use while in prison. This will include the provision of opioid substitution therapy and needle-syringe programmes.  This study highlights the vulnerability of prisoners to HIV, hepatitis B and hepatitis C and the need for harm reduction in prisons. At the same time, the study also highlights other adverse health outcomes relating to drug use or being in prison in terms of poor mental health outcomes among the sample. It illustrates an association between a measure of anxiety disorder and HIV infection. The strengths of this study lie in the large sample that were recruited from a broad range of prison facilities across the country, increasing the representativeness of the findings to all people living in prisons. Findings suggest an association between HIV infection and condomless sex, as well as a history of working in Russia and Ukraine. This suggests the potential for transmission of HIV across the region and points to the potential for sexual transmission of HIV in a region where transmission has been historically driven by injecting drug use. Findings contribute to the growing evidence for the urgent need for hepatitis C virus (HCV) treatment and increased access to needle-syringe programmes and opioid substitution therapy within prisons and communities in the region.  The high adherence among prisoners to HIV treatment demonstrates the provision of HCV treatment to the population is entirely feasible. Previous evidence from Russia has illustrated the difficulties for people living in prisons in maintaining HIV treatment post-release and this study underscores the need for support to facilitate the integration of individuals into harm reduction programmes including HIV treatment in community settings post-release. 

Europe
Azerbaijan
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Combination harm reduction may be more effective and cost-effective than partial approaches alone

The cost-effectiveness of harm reduction.

Wilson DP, Donald B, Shattock AJ, Wilson D, Fraser-Hurt N. Int J Drug Policy. 2015 Feb;26 Suppl 1:S5-11. doi: 10.1016/j.drugpo.2014.11.007. Epub 2014 Dec 1.

HIV prevalence worldwide among people who inject drugs (PWID) is around 19%. Harm reduction for PWID includes needle-syringe programs (NSPs) and opioid substitution therapy (OST) but often coupled with antiretroviral therapy (ART) for people living with HIV. Numerous studies have examined the effectiveness of each harm reduction strategy. This commentary discusses the evidence of effectiveness of the packages of harm reduction services and their cost-effectiveness with respect to HIV-related outcomes as well as estimate resources required to meet global and regional coverage targets. NSPs have been shown to be safe and very effective in reducing HIV transmission in diverse settings; there are many historical and very recent examples in diverse settings where the absence of, or reduction in, NSPs have resulted in exploding HIV epidemics compared to controlled epidemics with NSP implementation. NSPs are relatively inexpensive to implement and highly cost-effective according to commonly used willingness-to-pay thresholds. There is strong evidence that substitution therapy is effective, reducing the risk of HIV acquisition by 54% on average among PWID. OST is relatively expensive to implement when only HIV outcomes are considered; other societal benefits substantially improve the cost-effectiveness ratios to be highly favourable. Many studies have shown that ART is cost-effective for keeping people alive but there is only weak supportive, but growing evidence, of the additional effectiveness and cost-effectiveness of ART as prevention among PWID. Packages of combined harm reduction approaches are highly likely to be more effective and cost-effective than partial approaches. The coverage of harm reduction programs remains extremely low across the world. The total annual costs of scaling up each of the harm reduction strategies from current coverage levels, by region, to meet WHO guideline coverage targets are high with ART greatest, followed by OST and then NSPs. But scale-up of all three approaches is essential. These interventions can be cost-effective by most thresholds in the short-term and cost-saving in the long-term.

Abstract   Full-text [free] access

Editor’s notes: The spread of HIV among people who inject drugs has driven epidemics throughout regions of eastern Europe, and central and South-East Asia. In eastern Europe and central Asia, the majority of HIV infections have been attributed to injecting drug use. Some countries in the Middle East and North Africa region have also been experiencing rapidly emerging HIV epidemics among people who inject drugs. Harm reduction refers to methods of reducing health risks when eliminating them may not be possible. This paper provides a comprehensive review of evidence on the effectiveness and cost-effectiveness of different harm reduction approaches. These include needle- syringe programmes, opioid substitution therapy (OST), and antiretroviral therapy (ART), when implemented in different settings. Importantly, alongside considering the potential benefits of each approach separately, it makes the case that combination  prevention strategies are synergistic, and may achieve multiple impacts. Sadly still however, the coverage of harm reduction remains very low across the world. An estimated 90% of people who inject drugs worldwide are not accessing needle-syringe programmes, despite this being a highly effective and cost-effective programme. Along with the need for a greater investment in harm reduction, there are socio-political and legislative reasons for poor coverage of harm reduction. This cannot be improved without first addressing the stigma, discrimination and intolerance that restricts the expansion of harm reduction programmes in many settings. Addressing these barriers remains of paramount importance for facilitating effective harm reduction programmes. Encouragingly however, high OST coverage has been reported in Iran, Czech Republic and western Europe, and several countries in Asia and the Middle East have begun to scale-up their programmes. China has recently had the largest OST scale-up programme in the world. Uptake of ART by people living with HIV who inject drugs illustrates the largest disparities with what is required or deemed to be appropriate access. Only 14% of people living with HIV who inject drugs globally, have access to ART, with the largest gaps in ART provision in eastern Europe and central Asia. The further expansion of harm reduction is urgently needed, both to meet WHO targets, and to achieve the UNAIDS 90-90-90 target.

Asia, Europe, Oceania
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Further evidence to support Option B+: good HIV-free survival among children breastfed for a year with mothers on triple ART

Early infant feeding patterns and HIV-free survival: findings from the Kesho-Bora trial (Burkina Faso, Kenya, South Africa).

Cournil A, Van de Perre P, Cames C, de Vincenzi I, Read JS, Luchters S, Meda N, Naidu K, Newell ML, Bork K, Kesho Bora Study G. Pediatr Infect Dis J. 2015 Feb;34(2):168-74. doi: 10.1097/INF.0000000000000512.

Objective: To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association.

Methods: From June 2005 to August 2008, HIV-infected pregnant women were counseled regarding infant feeding options, and randomly assigned to triple-ARV prophylaxis (triple ARV) until breastfeeding cessation (BFC) before age 6 months or antenatal zidovudine with single-dose nevirapine (short-course ARV). Eighteen-month HIV-free survival of infants HIV-negative at 2 weeks of age was assessed by feeding patterns (replacement feeding from birth, BFC <3 months, BFC ≥3 months).

Results: Of the 753 infants alive and HIV-negative at 2 weeks, 28 acquired infection and 47 died by 18 months. Overall HIV-free survival at 18 months was 0.91 [95% confidence interval (CI): 0.88-0.93]. In the short-course ARV arm, HIV-free survival (0.88; CI: 0.84-0.91) did not differ by feeding patterns. In the triple ARV arm, overall HIV-free survival was 0.93 (CI: 0.90-0.95) and BFC <3 months was associated with lower HIV-free survival than BFC ≥3 months (adjusted hazard ratio: 0.36; CI: 0.15-0.83) and replacement feeding (adjusted hazard ratio: 0.20; CI: 0.04-0.94). In the triple ARV arm, 4 of 9 transmissions occurred after reported BFC (and 5 of 19 in the short-course arm), indicating that some women continued breastfeeding after interruption of ARV prophylaxis.

Conclusions: In resource-constrained settings, early weaning has previously been associated with higher infant mortality. We show that, even with maternal triple-ARV prophylaxis during breastfeeding, early weaning remains associated with lower HIV-free survival, driven in particular by increased mortality.

Abstract access 

Editor’s notes: Evaluating the impact of feeding patterns on infant HIV-free survival is essential for HIV prevention. This large, multi-country study was nested within the Kesha Bora randomised trial which found that triple ARV prophylaxis until cessation of breastfeeding was associated with lower rates of mother-to-child transmission than short-course ARV prophylaxis. Further analyses showed that in both arms, mortality in infants was highest when breastfeeding was stopped before three months of age. This analysis considered HIV-free survival and found that among mothers receiving triple ARV prophylaxis during breastfeeding, weaning before three months was associated with significantly lower HIV-free survival than longer breastfeeding or replacement feeding from birth. Overall, the results support the WHO 2013 ART guidelines which recommend initiation of triple ARV prophylaxis early in pregnancy, continued either through the breast feeding period (option B) or for life (option B+), and WHO recommendations for continued breastfeeding up to at least one year of age while on ART. 

Africa
Burkina Faso, Kenya, South Africa
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Negotiating the price for safe sex: A study among rural sex workers in Zimbabwe

The price of sex: condom use and the determinants of the price of sex among female sex workers in eastern Zimbabwe.

Elmes J, Nhongo K, Ward H, Hallett T, Nyamukapa C, White PJ, Gregson S. J Infect Dis. 2014 Dec 1;210 Suppl 2:S569-78. doi: 10.1093/infdis/jiu493.

Background: Higher prices for unprotected sex threaten the high levels of condom use that contributed to the decline in Zimbabwe's human immunodeficiency virus (HIV) epidemic. To improve understanding of financial pressures competing against safer sex, we explore factors associated with the price of commercial sex in rural eastern Zimbabwe.

Methods: We collected and analyzed cross-sectional data on 311 women, recruited during October-December 2010, who reported that they received payment for their most-recent or second-most-recent sex acts in the past year. Zero-inflated negative binomial models with robust standard errors clustered on female sex worker (FSW) were used to explore social and behavioral determinants of price.

Results: The median price of sex was $10 (interquartile range [IQR], $5-$20) per night and $10 (IQR, $5-$15) per act. Amounts paid in cash and commodities did not differ significantly. At the most-recent sex act, more-educated FSWs received 30%-74% higher payments. Client requests for condom use significantly predicted protected sex (P < .01), but clients paid on average 42.9% more for unprotected sex.

Conclusions: Within a work environment where clients' preferences determine condom use, FSWs effectively use their individual capital to negotiate the terms of condom use. Strengthening FSWs' preferences for protected sex could help maintain high levels of condom use.

Abstract  Full-text [free] access

Editor’s notes: This study addresses a relatively neglected issue of how payments for commercial sex among rural sex workers are determined, and which factors are important to price negotiations. In this study from Zimbabwe, the participants were grouped into “more professional”, both the last two clients were commercial, (FSW2) and “less professional”, one of the last two clients was commercial (FSW1). The “more professional” sex workers effectively negotiated transactions, with unprotected sex increasing the mean payment by almost a half, compared with protected sex. This differential pricing was not seen for the “less professional” sex workers, perhaps reflecting limited capacity to negotiate with clients. This study demonstrates the importance of strengthening preferences for protected sex, among female sex workers, including among less visible sex workers. Such strategies may include enhancing social capital and collective action, e.g. collective price-fixing to reduce competitive pressure to engage in unsafe sex. 

Africa
Zimbabwe
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Abstinence from breastfeeding: further evidence of the risks

Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study.

Bork KA, Cournil A, Read JS, Newell ML, Cames C, Meda N, Luchters S, Mbatia G, Naidu K, Gaillard P, de Vincenzi I. Am J Clin Nutr. 2014 Dec;100(6):1559-68. doi: 10.3945/ajcn.113.082149. Epub 2014 Oct 22.

Background: Refraining from breastfeeding to prevent HIV transmission has been associated with increased morbidity and mortality in HIV-exposed African infants.

Objective: The objective was to assess risks of common and serious infectious morbidity by feeding mode in HIV-exposed, uninfected infants ≤6 mo of age with special attention to the issue of reverse causality.

Design: HIV-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the prevention of mother-to-child transmission Kesho Bora trial and counseled to either breastfeed exclusively and cease by 6 mo postpartum or formula feed exclusively. Maternal-reported morbidity (fever, diarrhea, and vomiting) and serious infectious events (SIEs) (gastroenteritis and lower respiratory tract infections) were investigated for 751 infants for 2 age periods (0-2.9 and 3-6 mo) by using generalized linear mixed models with breastfeeding as a time-dependent variable and adjustment for study site, maternal education, economic level, and cotrimoxazole prophylaxis.

Results: Reported morbidity was not significantly higher in nonbreastfed compared with breastfed infants [OR: 1.31 (95% CI: 0.97, 1.75) and 1.21 (0.90, 1.62) at 0-2.9 and 3-6 mo of age, respectively]. Between 0 and 2.9 mo of age, never-breastfed infants had increased risks of morbidity compared with those of infants who were exclusively breastfed (OR: 1.49; 95% CI: 1.01, 2.2; P = 0.042). The adjusted excess risk of SIEs in nonbreastfed infants was large between 0 and 2.9 mo (OR: 6.0; 95% CI: 2.2, 16.4; P = 0.001). Between 3 and 6 mo, the OR for SIEs was sensitive to the timing of breastfeeding status, i.e., 4.3 (95% CI: 1.2, 15.3; P = 0.02) when defined at end of monthly intervals and 2.0 (95% CI: 0.8, 5.0; P = 0.13) when defined at the beginning of intervals. Of 52 SIEs, 3 mothers reported changes in feeding mode during the SIE although none of the mothers ceased breastfeeding completely.

Conclusions: Not breastfeeding was associated with increased risk of serious infections especially between 0 and 2.9 mo of age.

Abstract access 

Editor’s notes: Abstinence from breastfeeding or early weaning is known to be associated with higher mortality among infants born to women living with HIV. The risk of mother-to-child HIV transmission through breast-milk can be reduced by the use of antiretroviral therapies. Mothers living with HIV are advised to continue breastfeeding throughout infancy, while on therapy. The aim of this study was to investigate the association between breastfeeding and infection risk, accounting for reverse causality (i.e. mothers changing feeding mode in response to infant illness). Non-breastfed infants were at higher risk of serious infectious events than breastfed infants, as expected, and particularly among infants aged under three months. There was no evidence of a difference in reported morbidity. A qualitative assessment of the reverse causality found that some 94% of mothers reported not changing the feeding mode as a consequence of serious infectious events. The strengths of this study are that only HIV-exposed, but HIV-negative infants were included, and a range of sensitivity analyses were conducted. A limitation is that infant feeding data may be subject to reporting bias. This study has confirmed the findings of earlier research, and reassuringly found limited evidence to suggest reverse causality between breastfeeding and serious infectious outcomes.

Africa
Burkina Faso, Kenya, South Africa
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Per-act HIV transmission risk during anal sex may be higher than previously thought

Estimating per-act HIV transmission risk: a systematic review.

Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. AIDS. 2014 Jun 19;28(10):1509-19. doi: 10.1097/QAD.0000000000000298.

Background: Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy.

Methods: We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7 339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8 119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors.

Results: Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10 000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner.

Conclusion: The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

Abstract access 

Editor’s notes: The study updates the 2005 Centres for Disease Control (CDC) per-act HIV transmission risks with estimates from recent publications. In addition, it summarizes the effects of various co-factors that modify the transmission risks during sexual exposure. These include genital ulcer disease, viral load, disease stage, use of antiretrovirals, condom use and male circumcision. However, estimates from low-income countries on sexual and mother-to-child transmission are very heterogeneous and not included in the analyses. In general, the updated estimates of transmission risks are comparable to figures from the 2005 CDC study. But they also suggest that the transmission probabilities for both receptive and insertive anal intercourse could be higher than previously thought. Further, the study reasserts that the per-act risk for all sexual exposures is substantially attenuated through the use of condoms and antiretrovirals. These new estimates will be important for both modelling studies and prevention programmes. But a better understanding of HIV transmission risks in low-income countries is needed. 

Asia, Northern America, Oceania
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Correlations between socioeconomic factors and needle sharing among methamphetamine users

Correlates of shared methamphetamine injection among methamphetamine-injecting treatment seekers: the first report from Iran.

Mehrjerdi ZA, Abarashi Z, Noroozi A, Arshad L, Zarghami M. Int J STD AIDS. 2014 May;25(6):420-7. doi: 10.1177/0956462413512806. Epub 2013 Nov 28.

Shared methamphetamine injection is an emerging route of drug use among Iranian methamphetamine injectors. It is a primary vector for blood-borne infections. The aim of the current study is to determine the prevalence and correlates of shared methamphetamine injection in a sample of Iranian methamphetamine injecting treatment seekers in the south of Tehran. We surveyed male and female methamphetamine injectors at three drop-in centres and 18 drug-use community treatment programmes. Participants reported socio-demographic characteristics, drug use, high-risk behaviours, current status of viral infections and service use for drug treatment. Bivariate and multivariate logistic regression models were used to test associations between participants' characteristics and shared methamphetamine injection. Overall, 209 clients were recruited; 90.9% were male; 52.6% reported current methamphetamine injection without any shared injection behaviour and 47.4% reported current shared methamphetamine injection. Shared methamphetamine injection was found to be primarily associated with living with sex partners (AOR 1.25, 95% CI 1.13-1.98), reporting ≥3 years of dependence on methamphetamine injection (AOR 1.61, 95% CI 1.27-2.12), injection with pre-filled syringes in the past 12 months (AOR 1.96, 95% CI 1.47-2.42), homosexual sex without condom use in the past 12 months (AOR 1.85, 95% CI 1.21-2.25), the paucity of NA group participation in the past 12 months (AOR 0.67, 95% CI 0.41-0.99), the paucity of attending psychotherapeutic sessions in the past 12 months (AOR 0.44, 95% CI 0.28-0.96) and positive hepatitis C status (AOR 1.98, 95% CI 1.67-2.83). Deeper exploration of the relationship between shared methamphetamine injection and sexual risk among Iranian methamphetamine injectors would benefit HIV/sexually transmitted infection prevention efforts. In addition, existing psychosocial interventions for methamphetamine-injecting population may need to be adapted to better meet the risks of shared methamphetamine injectors.

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Editor’s notes: This study highlights an important area. The authors demonstrate several links between socioeconomic factors and shared needle use among methamphetamine (MA) users. Multi-person use of contaminated injecting equipment was strongly associated with homelessness and with joblessness. Further, people who engaged in multi-use of contaminated needles were more likely to be divorced or separated than people who did not engage in this practice. People who shared needles were also more likely to be living with sex partners than people who do not. The authors suggest that this is because shared injection might be used as a way of expressing love, support, and care. Duration of dependence on MA injection was also associated with the practice of multi-person use of contaminated injecting equipment. People who used MA for three years or more were more likely to share needles than those who had MA use for a shorter time. The authors also found that participants with low attendance at counselling sessions for people who inject drugs were more likely to be needle sharers. An association between multi-person use of contaminated injecting equipment and hepatitis C infection was also found.

Despite the compelling findings, this study has some limitations. The investigators employ a relatively small sample size which is mainly comprised of men, some 90.9%, making it difficult to generalize findings to a wider population. That said, this study is one of the first of its kind and highlights an area where more research is needed. 

Asia
Iran (Islamic Republic of)
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