Articles tagged as "Zimbabwe"

Tenofovir-based regimens improve outcomes in HIV-HBV co-infection

Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: outcomes through 144 weeks.

Thio CL, Smeaton L, Hollabaugh K, Saulynas M, Hwang H, Saravanan S, Kulkarni S, Hakim J, Nyirenda M, Iqbal HS, Lalloo UG, Campbell TB, Lockman S, Currier JS. AIDS. 2015 Jun 19;29(10):1173-82. doi: 10.1097/QAD.0000000000000686.

Objectives: To explore factors associated with short and long-term hepatitis B virus (HBV) DNA suppression in a multinational cohort of HIV-HBV co-infected patients receiving HBV-active antiretrovirals.

Methods: One hundred and fifteen HIV-HBV co-infected patients participating in one of the two global randomized clinical trials conducted by the Adult AIDS Clinical Trials Group of different antiretroviral regimens received either HBV monotherapy with either lamivudine or emtricitabine (N = 56), or HBV dual therapy with tenofovir disoproxil fumarate (TDF) + lamivudine or emtricitabine (N = 59). Associations of pretreatment characteristics with the primary (HBV DNA <200 IU/ml at 24 weeks) and longitudinal outcomes through 144 weeks were explored using logistic regression. HBV drug-resistance mutations were determined by pol sequencing in those with viral rebound.

Results: The proportion with HBV DNA below 200 IU/ml was 60% (95% confidence interval 50-69%) at 24 weeks and 79% (95% confidence interval 69-88%) at 144 weeks. Pretreatment factors associated with the primary outcome were HBV DNA, CD4 T-cell count, and aspartate aminotransferase, but only pretreatment HBV DNA remained associated with long-term suppression (P < 0.0001). HBV therapy group was not significantly associated with the primary outcome at 24 weeks; however, longitudinally, a greater proportion in the dual-therapy group achieved HBV DNA below 200 IU/ml (P = 0.007). A higher proportion of hepatitis B e antigen-negative patients (n = 57) achieved HBV DNA below 200 IU/ml at any point, regardless of the therapy group. All 12 patients with emergence of lamivudine-resistant mutants were in the monotherapy group.

Conclusions: TDF-based dual HBV-active antiretroviral therapy is preferred to treat HIV-HBV co-infected patients. In resource-limited settings in which TDF may not be universally available, lamivudine or emtricitabine HBV monotherapy is a reasonable option in patients with low HBV replication.

Abstract access 

Editor’s notes: Hepatitis B virus infection remains a leading cause of preventable morbidity and mortality globally, through cirrhosis and liver cancer. In settings with a high prevalence of HIV-HBV coinfection, there is an opportunity to optimise clinical management within the public health approach to antiretroviral therapy. This study adds to the evidence base suggesting that antiretroviral regimens containing lamivudine/emtricitabine and tenofovir are associated with better virologic outcomes than regimens without tenofovir for people co-infected with HIV and HBV. In this study, a post hoc analysis of two multicentre randomised controlled trials, regimens with two HBV-active agents provided more durable virologic suppression and limited the emergence of lamivudine-resistant HBV strains. Although recommendations about the treatment of HIV-HBV coinfection are incorporated into WHO antiretroviral guidelines, testing for HBV infection within antiretroviral programmes is still uncommon and tenofovir is not universally employed in standard first-line antiretroviral regimens. With an increasing number of people switching to second-line antiretroviral regimens, there is the additional challenge of identifying HBV infection in order to maintain HBV-active agents within the second-line regimen. There is now a need for better evidence around how to operationalise these recommendations within national antiretroviral programmes.        

Comorbidity, HIV Treatment
Africa, Asia, Latin America
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Expansions in HIV treatment believed to reduce HIV stigma

HIV treatment scale-up and HIV-related stigma in sub-Saharan Africa: a longitudinal cross-country analysis.

Chan BT, Tsai AC, Siedner MJ. Am J Public Health. 2015 Jun 11:e1-e7. [Epub ahead of print] doi:10.2105/AJPH.2015.302716

Objectives: We estimated the association between antiretroviral therapy (ART) uptake and HIV-related stigma at the population level in sub-Saharan Africa.

Methods: We examined trends in HIV-related stigma and ART coverage in sub-Saharan Africa during 2003 to 2013 using longitudinal, population-based data on ART coverage from the Joint United Nations Program on HIV/AIDS and on HIV-related stigma from the Demographic and Health Surveys and AIDS Indicator Surveys. We fitted 2 linear regression models with country fixed effects, with the percentage of men or women reporting HIV-related stigma as the dependent variable and the percentage of people living with HIV on ART as the explanatory variable.

Results: Eighteen countries in sub-Saharan Africa were included in our analysis. For each 1% increase in ART coverage, we observed a statistically significant decrease in the percentage of women (b = -0.226; P = .007; 95% confidence interval [CI] = -0.383, -0.070) and men (b = -0.281; P = .009; 95% CI = -0.480, -0.082) in the general population reporting HIV-related stigma.

Conclusions: An important benefit of ART scale-up may be the diminution of HIV-related stigma in the general population. .

Abstract access 

Editor’s notes: Focused on sub-Saharan Africa, this study suggests that a benefit of the scale-up of antiretroviral therapy (ART) may have been a reduction in HIV-associated stigma. The authors combine data on HIV-associated stigma from the Demographic and Health Surveys and AIDS Indicator Surveys with data on ART coverage from UNAIDS. The results are presented for each of 18 countries and the authors suggest that increases in ART coverage are correlated with decreasing stigma, especially among countries with high HIV prevalence. The authors hypothesise that by allowing a person with HIV to experience a healthier life, ART reduces the stigma of HIV’s association with moral deviance. The authors also attribute knowledge to decreases in stigma.

While addressing an interesting and important question, the paper has some limitations. We suggest that participant responses to questions about whether they would be willing to care for someone “sick with AIDS”, and whether they would want a family member to keep an AIDS diagnosis “secret” cannot safely be interpreted as reflecting stigmatising attitudes or anticipated stigma. It would have been interesting to know if the methods used in the analysis could assess the role of ART relative to other factors in being associated with any changes over time in HIV-associated stigma.

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The impact of cash transfers on orphans and other children made vulnerable by HIV

Effects of cash transfers on children's health and social protection in sub-Saharan Africa: differences in outcomes based on orphan status and household assets.

Crea TM, Reynolds AD, Sinha A, Eaton JW, Robertson LA, Mushati P, Dumba L, Mavise G, Makoni JC, Schumacher CM, Nyamukapa CA, Gregson S. BMC Public Health. 2015 May 28;15:511. doi: 10.1186/s12889-015-1857-4.

Background: Unconditional and conditional cash transfer programmes (UCT and CCT) show potential to improve the well-being of orphans and other children made vulnerable by HIV/AIDS (OVC). We address the gap in current understanding about the extent to which household-based cash transfers differentially impact individual children's outcomes, according to risk or protective factors such as orphan status and household assets.

Methods: Data were obtained from a cluster-randomised controlled trial in eastern Zimbabwe, with random assignment to three study arms - UCT, CCT or control. The sample included 5331 children ages 6-17 from 1697 households. Generalized linear mixed models were specified to predict OVC health vulnerability (child chronic illness and disability) and social protection (birth registration and 90% school attendance). Models included child-level risk factors (age, orphan status); household risk factors (adults with chronic illnesses and disabilities, greater household size); and household protective factors (including asset-holding). Interactions were systematically tested.

Results: Orphan status was associated with decreased likelihood for birth registration, and paternal orphans and children for whom both parents' survival status was unknown were less likely to attend school. In the UCT arm, paternal orphans fared better in likelihood of birth registration compared with non-paternal orphans. Effects of study arms on outcomes were not moderated by any other risk or protective factors. High household asset-holding was associated with decreased likelihood of child's chronic illness and increased birth registration and school attendance, but household assets did not moderate the effects of cash transfers on risk or protective factors.

Conclusion: Orphaned children are at higher risk for poor social protection outcomes even when cared for in family-based settings. UCT and CCT each produced direct effects on children's social protection which are not moderated by other child- and household-level risk factors, but orphans are less likely to attend school or obtain birth registration. The effects of UCT and CCT are not moderated by asset-holding, but greater household assets predict greater social protection outcomes. Intervention efforts need to focus on ameliorating the additional risk burden carried by orphaned children. These efforts might include caregiver education, and additional incentives based on efforts made specifically for orphaned children.

Abstract  Full-text [free] access

Editor’s notes: In sub-Saharan Africa, there is growing evidence on the impact of cash transfers on youth HIV risk, health outcomes of orphans and other children made vulnerable by HIV and on social protection outcomes such as school attendance. Using data from a cluster randomised controlled trial in Zimbabwe, the authors sought to understand the extent to which individual level children’s risk factors and household asset accumulation influence the effects of cash transfers on child health (chronic illness and disability) and child social protection (birth registration status and school attendance) outcomes.

There was no evidence to illustrate that the type of orphan status, maternal or paternal or both, was associated with child disability or chronic illness. There was some evidence that suggested that orphan status predicted social vulnerability, i.e., risk for not obtaining birth registration. However the receipt of an unconditional cash transfer buffered this risk for paternal orphans, suggesting birth registration being a gendered activity and that mothers of paternal orphans might use cash incentives to invest in the human capital of their children. Results also demonstrate that cash transfers, both unconditional and conditional, and household accumulation of assets have positive effects on social protection outcomes including birth registration and school attendance, separately. But the effect of cash transfers is not influenced by the amount of assets held by a household. Furthermore, in contrast to other studies, there is no evidence from these findings to illustrate that cash transfers have an effect on health outcomes. However, asset holding seems to have a weak, but positive effect on children’s chronic illness, but no effect on chronic disability. This suggests that households with some assets are able to use these assets to access health care services to treat chronic illness. Furthermore these households with greater assets may also experience better living conditions which perhaps contribute to better health outcomes.

Given the financial burden of HIV on households caring for orphan and vulnerable children, programme efforts for HIV prevention should focus on addressing this burden. This study contributes to the evidence base from other countries in sub-Saharan Africa.  Findings from Malawi and Kenya, for example, have illustrated that the provision of cash transfers to HIV affected households provide a substantial boost that is effective in improving outcomes among vulnerable children, in particular certain social protection outcomes, such as school attendance.

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Need for further water, sanitation and hygiene programmes among people living with HIV

The impact of water, sanitation, and hygiene interventions on the health and well-being of people living with HIV: a systematic review.

Yates T, Lantagne D, Mintz E, Quick R. J Acquir Immune Defic Syndr. 2015 Apr 15;68 Suppl 3:S318-30. doi: 10.1097/QAI.0000000000000487.

Background: Access to improved water supply and sanitation is poor in low-income and middle-income countries. Persons living with HIV/AIDS (PLHIV) experience more severe diarrhea, hospitalizations, and deaths from diarrhea because of waterborne pathogens than immunocompetent populations, even when on antiretroviral therapy (ART).

Methods: We examined the existing literature on the impact of water, sanitation, and hygiene (WASH) interventions on PLHIV for these outcomes: (1) mortality, (2) morbidity, (3) retention in HIV care, (4) quality of life, and (5) prevention of ongoing HIV transmission. Cost-effectiveness was also assessed. Relevant abstracts and articles were gathered, reviewed, and prioritized by thematic outcomes of interest. Articles meeting inclusion criteria were summarized in a grid for comparison.

Results: We reviewed 3355 citations, evaluated 132 abstracts, and read 33 articles. The majority of the 16 included articles focused on morbidity, with less emphasis on mortality. Contaminated water, lack of sanitation, and poor hygienic practices in homes of PLHIV increase the risk of diarrhea, which can result in increased viral load, decreased CD4 counts, and reduced absorption of nutrients and antiretroviral medication. We found WASH programming, particularly water supply, household water treatment, and hygiene interventions, reduced morbidity. Data were inconclusive on mortality. Research gaps remain in retention in care, quality of life, and prevention of ongoing HIV transmission. Compared with the standard threshold of 3 times GDP per capita, WASH interventions were cost-effective, particularly when incorporated into complementary programs.

Conclusions: Although research is required to address behavioral aspects, evidence supports that WASH programming is beneficial for PLHIV.

Abstract access 

Editor’s notes: Researchers, implementers, and policy makers have been examining how to better integrate programmes with overlapping burdens of morbidity and mortality. This paper illustrates how access to clean water and good sanitation practices, or lack thereof, can impact the health of people living with HIV. Water, sanitation, and hygiene (WASH) programmes can improve the negative effects poor water quality and bad sanitation have on people living with HIV. They reduce or even eliminate diarrheal infections, which allow for better absorption of HIV treatment medication that leads to a reduction in viral load and increased CD4 counts. While this systematic review revealed evidence on the reduced burden of morbidity that WASH programmes can confer, little has been done in the way of research linking WASH programmes to mortality in people living with HIV, nor how they may affect adherence or retention in care. Side effects of HIV treatment is a common reason why people stop taking medications, and common side effects are nausea and diarrhoea. It is possible that intestinal issues caused by unsafe drinking water could exacerbate the impact of side effects on people already experiencing them, therefore reducing motivation to continue taking their ARVs. This paper also suggests that synergies in cost sharing and increasing cost effectiveness could be achieved by integrating programmes. However further research is necessary to fully understand the logistical and cost implications.


Africa, Asia
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Oral and vaginal pre-exposure prophylaxis: no evidence of benefit among young African women

Tenofovir-based pre-exposure prophylaxis for HIV infection among African women.

Marrazzo JM, Ramjee G, Richardson BA, Gomez K, Mgodi N, Nair G, Palanee T, Nakabiito C, van der Straten A, Noguchi L, Hendrix CW, Dai JY, Ganesh S, Mkhize B, Taljaard M, Parikh UM, Piper J, Masse B, Grossman C, Rooney J, Schwartz JL, Watts H, Marzinke MA, Hillier SL, McGowan IM, Chirenje ZM, VOICE Study Team. N Engl J Med. 2015 Feb 5;372(6):509-18. doi: 10.1056/NEJMoa1402269.

Background: Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.

Methods: We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as pre-exposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.

Results: Of 12 320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events.

Conclusions: None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.

Abstract   Full-text [free] access

Editor’s notes: Randomised controlled trials across a range of settings and populations have demonstrated a benefit of antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV acquisition, when adherence is high. This study compared two oral PreP regimens and a vaginal gel against placebo oral/gel among predominantly young, unmarried women in South Africa, Uganda and Zimbabwe. There was no evidence of a difference in HIV incidence between the groups. Although self-reported adherence was good, as estimated by the amount of product returned, or in interviews, tenofovir (TFV) was detected in only 25-30% of plasma samples analysed. TFV detection in plasma at the first quarterly visit was associated with both TFV detection at later visits and lower risk of HIV acquisition. But this may be partly confounded by differences in HIV exposure which were not measured. This trial has important implications for HIV prevention and implementation of programmes with proven efficacy. This includes the fact that HIV incidence continues to be high in some settings despite increasing coverage of ART. There is a need to assess products with sustained delivery of ART, e.g. vaginal rings or injections, and for real-time monitoring of biomarkers for adherence rather than reliance on self-report and returned-product count.

South Africa, Uganda, Zimbabwe
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High risk of death among adolescents while awaiting ART

Risk of death among those awaiting treatment for HIV infection in Zimbabwe: adolescents are at particular risk.

Shroufi A, Ndebele W, Nyathi M, Gunguwo H, Dixon M, Saint-Sauveur JF, Taziwa F, Vinoles MC, Ferrand RA. J Int AIDS Soc. 2015 Feb 23;18(1):19247. doi: 10.7448/IAS.18.1.19247. eCollection 2015.

Introduction: Mortality among HIV-positive adults awaiting antiretroviral therapy (ART) has previously been found to be high. Here, we compare adolescent pre-ART mortality to that of adults in a public sector HIV care programme in Bulawayo, Zimbabwe.

Methods: In this retrospective cohort study, we compared adolescent pre-ART outcomes with those of adults enrolled for HIV care in the same clinic. Adolescents were defined as those aged 10-19 at the time of registration. Comparisons of means and proportions were carried out using two-tailed sample t-tests and chi-square tests respectively, for normally distributed data, and the Mann-Whitney U-tests for non-normally distributed data. Loss to follow-up (LTFU) was defined as missing a scheduled appointment by three or more months.

Results: Between 2004 and 2010, 1382 of 1628 adolescents and 7557 of 11 106 adults who registered for HIV care met the eligibility criteria for ART. Adolescents registered at a more advanced disease stage than did adults (83% vs. 73% WHO stage III/IV, respectively, p<0.001), and the median time to ART initiation was longer for adolescents than for adults [21 (10-55) days vs. 15 (7-42) days, p<0.001]. Among the 138 adolescents and 942 adults who never commenced ART, 39 (28%) of adolescents and 135 (14%) of adults died, the remainder being LTFU. Mortality among treatment-eligible adolescents awaiting ART was significantly higher than among adults (3% vs. 1.8%, respectively, p=0.004).

Conclusions: Adolescents present to ART services at a later clinical stage than adults and are at an increased risk of death prior to commencing ART. Improved and innovative HIV case-finding approaches and emphasis on prompt ART initiation in adolescents are urgently needed. Following registration, defaulter tracing should be used, whether or not ART has been commenced.

Abstract  Full-text [free] access

Editor’s notes: In this article the pre-antiretroviral therapy (ART) outcomes of adolescents (persons between 10 and 19 years) registered in a well-established ART programme in Zimbabwe between 2004 and 2010 are compared to those of adults. The authors found that adolescents living with HIV experience a higher risk of death while awaiting ART initiation. This is most likely due to the more advanced stage of HIV infection at the time of registration. Most adolescents in this study had acquired HIV at birth and underwent HIV testing following an HIV-associated illness. Treatment-eligible adolescents also waited significantly longer than adults to initiate ART. Under-preparedness to start ART, and reduced access to transport among adolescents were cited as possible reasons for this delay. The authors suggest that adolescents may be at higher risk of mortality because of the longer duration of having lived with untreated infection. They are therefore less able to afford further delays before starting ART. The authors therefore suggest prompt ART initiation for treatment-eligible adolescents. They emphasize the need for innovative methods of HIV case-finding for adolescents. Adolescents are often suspicious of health care workers, resulting in reduced uptake of health services, including HIV testing. To provide more effective HIV counselling and testing for adolescents, WHO has recognised adolescents as an important population for HIV prevention, and developed specific HIV testing guidelines in 2013.

Interestingly the authors suggest using 12-month mortality among ART-eligible individuals, whether on ART or not, as a programme indicator. Incorporating pre-ART deaths, which are often unrecorded, and deaths among individuals newly started on ART, which may be partly attributed to pre-ART delays, indicates how well a programme manages people from the time they are registered in care. This could provide a more inclusive estimate of programme quality. 

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Adolescent adherence to antiretroviral therapy: what matters?

Factors associated with adherence to antiretroviral therapy among adolescents living with HIV/AIDS in low- and middle-income countries: a systematic review.

Hudelson C, Cluver L. AIDS Care. 2015 Feb 23:1-12. [Epub ahead of print]

Adolescents living in low- and middle-income countries (LMICs) are disproportionately burdened by the global HIV/AIDS pandemic. Maintaining medication adherence is vital to ensuring that adolescents living with HIV/AIDS receive the benefits of antiretroviral therapy (ART), although this group faces unique challenges to adherence. Knowledge of the factors influencing adherence among people during this unique developmental period is needed to develop more targeted and effective adherence-promoting strategies. This systematic review summarizes the literature on quantitative observational studies examining correlates, including risk and resilience-promoting factors, of ART adherence among adolescents living with HIV/AIDS in LMICs. A systematic search of major electronic databases, conference-specific databases, gray literature, and reference lists of relevant reviews and documents was conducted in May 2014. Included studies examined relationships between at least one factor and ART adherence as an outcome and were conducted in primarily an adolescent population (age 10-19) in LMICs. The search identified 7948 unique citations from which 15 studies fit the inclusion criteria. These 15 studies identified 35 factors significantly associated with ART adherence representing a total of 4363 participants across nine different LMICs. Relevant studies revealed few consistent relationships between measured factors and adherence while highlighting potentially important themes for ART adherence including the impact of (1) adolescent factors such as gender and knowledge of serostatus, (2) family structure, (3) the burdensome ART regimens, route of administration, and attitudes about medication, and (4) health care and environmental factors, such as rural versus urban location and missed clinic appointments. Rates of adherence across studies ranged from 16% to 99%. This review identifies unique factors significantly related to ART adherence among adolescents living in LMICs. More research using longitudinal designs and rigorous measures of adherence is required in order to identify the range of factors influencing ART adherence as adolescents living with HIV/AIDS in LMICs grow into adulthood.

Abstract access 

Editor’s notes: Expanded access to antiretroviral therapy (ART) and scale-up of programmes to prevent mother-to-child HIV transmission has resulted in the burden of paediatric HIV infection shifting onto adolescents, in low- and middle-income countries. Adolescents and young adults account for 41% of incident infections globally and are the only age group for which AIDS-associated deaths have risen in the past decade.

As the number of adolescents on ART increases, sustaining optimal adherence has emerged as the key challenge. While there are limited adolescent-specific data available, estimates of ART adherence suggest that adolescents have much poorer adherence than adults. This leads to increased risk of disease progression, transmission to sexual partners and antiretroviral drug resistance.

There is a growing body of literature that has examined factors affecting adherence, but to date the focus has been on adults and young children. Therefore, this systematic review of factors associated with good and suboptimal adherence specifically among adolescents aged 10 to 19 years, is timely.

There were a diverse range of factors associated with adherence across the fifteen studies considered. These include knowledge of serostatus, the influence of family structure, burdensome regimens, route of administration (caregiver giving medication versus adolescent self-medicating), and attitudes about medication and missed appointments. These factors likely interact with the complexities faced during adolescence to increase the risk of suboptimal adherence.   

The studies considered in this review had significant weaknesses. Firstly, most studies were cross-sectional. Therefore the extent to which causality between the considered factors and adherence can be inferred is limited. Secondly, not all studies reported on the strengths of the relationship between the factors and adherence or accounted for confounding. Thirdly, the method of measuring adherence varied between studies. Only one study in the review used a gold standard, objective treatment outcome measure, HIV viral load.

Notwithstanding these limitations, this is the first study to examine correlates of adherence to ART in adolescence. Although there were few consistent relationships between these factors and adherence, the study does suggest potential activities to improve adherence.

Given the central role of adolescents in determining the trajectory of the HIV epidemic, there is a need for more rigorous research to define factors affecting adherence behaviours among adolescents. Programmes addressing important risk- and resilience-promoting factors such as caregiver support and less burdensome regimens have potential to improve adherence. 

Africa, Asia, Europe, Latin America
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Further evidence of an association with the injectable contraceptive, depot-medroxyprogesterone acetate with risk of HIV

Hormonal contraception and the risk of HIV acquisition: an individual participant data meta-analysis.

Morrison CS, Chen PL, Kwok C, Baeten JM, Brown J, Crook AM, Van Damme L, Delany-Moretlwe S, Francis SC, Friedland BA, Hayes RJ, Heffron R, Kapiga S, Karim QA, Karpoff S, Kaul R, McClelland RS, McCormack S, McGrath N, Myer L, Rees H, van der Straten A, Watson-Jones D, van de Wijgert JH, Stalter R, Low N. PLoS Med. 2015 Jan 22;12(1):e1001778. doi: 10.1371/journal.pmed.1001778. eCollection 2015.

Background: Observational studies of a putative association between hormonal contraception (HC) and HIV acquisition have produced conflicting results. We conducted an individual participant data (IPD) meta-analysis of studies from sub-Saharan Africa to compare the incidence of HIV infection in women using combined oral contraceptives (COCs) or the injectable progestins depot-medroxyprogesterone acetate (DMPA) or norethisterone enanthate (NET-EN) with women not using HC.

Methods and findings: Eligible studies measured HC exposure and incident HIV infection prospectively using standardized measures, enrolled women aged 15-49 y, recorded ≥15 incident HIV infections, and measured prespecified covariates. Our primary analysis estimated the adjusted hazard ratio (aHR) using two-stage random effects meta-analysis, controlling for region, marital status, age, number of sex partners, and condom use. We included 18 studies, including 37 124 women (43 613 woman-years) and 1830 incident HIV infections. Relative to no HC use, the aHR for HIV acquisition was 1.50 (95% CI 1.24-1.83) for DMPA use, 1.24 (95% CI 0.84-1.82) for NET-EN use, and 1.03 (95% CI 0.88-1.20) for COC use. Between-study heterogeneity was mild (I2 < 50%). DMPA use was associated with increased HIV acquisition compared with COC use (aHR 1.43, 95% CI 1.23-1.67) and NET-EN use (aHR 1.32, 95% CI 1.08-1.61). Effect estimates were attenuated for studies at lower risk of methodological bias (compared with no HC use, aHR for DMPA use 1.22, 95% CI 0.99-1.50; for NET-EN use 0.67, 95% CI 0.47-0.96; and for COC use 0.91, 95% CI 0.73-1.41) compared to those at higher risk of bias (pinteraction = 0.003). Neither age nor herpes simplex virus type 2 infection status modified the HC-HIV relationship.

Conclusions: This IPD meta-analysis found no evidence that COC or NET-EN use increases women's risk of HIV but adds to the evidence that DMPA may increase HIV risk, underscoring the need for additional safe and effective contraceptive options for women at high HIV risk. A randomized controlled trial would provide more definitive evidence about the effects of hormonal contraception, particularly DMPA, on HIV risk.

Abstract  Full-text [free] access

Editor’s notes: As seen in the paper published this month by Ralph et al, observational studies have reported that hormonal contraception, in particular injectable progestins depot-medroxyprogesterone acetate (DMPA), may increase risk of HIV infection. This individual patient data meta-analysis adds further to the evidence. A major strength of the study is the large sample size. It provides sufficient power to examine associations between specific contraceptives and HIV risk and to investigate effect modification in pre-specified sub-group analyses. Furthermore, using individual-level data allowed a consistent approach to coding and adjustment for confounding. If the association is real, this has important implications for sexual and reproductive health in areas of sub-Saharan Africa where the incidence of HIV acquisition and unintended pregnancy is high.



Hormonal contraceptive use and women's risk of HIV acquisition: a meta-analysis of observational studies.

Ralph LJ, McCoy SI, Shiu K, Padian NS. Lancet Infect Dis. 2015 Jan 8. pii: S1473-3099(14)71052-7. doi: 10.1016/S1473-3099(14)71052-7. [Epub ahead of print]

Background: The evidence from epidemiological research into whether use of hormonal contraception increases women's risk of HIV acquisition is inconsistent. We did a robust meta-analysis of existing data to provide summary estimates by hormonal contraceptive method which can be used to inform contraceptive guidelines, models, and future studies.

Methods: We updated a recent systematic review to identify and describe studies that met inclusion criteria. To ensure inclusion of more recent research, we searched PubMed for articles published after December, 2011, using the terms "hormonal contraception", "HIV/acquisition", "injectables", "progestin", and "oral contraceptive pills". We assessed statistical heterogeneity for these studies, and, when appropriate, combined point estimates by hormonal contraception formulation using random-effects models. We assessed publication bias and investigated heterogeneity through subgroup and stratified analyses according to study population and design features.

Findings: We identified 26 studies, 12 of which met inclusion criteria. There was evidence of an increase in HIV risk in the ten studies of depot medroxyprogesterone acetate (pooled hazard ratio [HR] 1.40, 95% CI 1.16-1.69). This risk was lower in the eight studies done in women in the general population (pooled HR 1.31, 95% CI 1.10-1.57). There was substantial between-study heterogeneity in secondary analyses of trials (n=7, I2 51.1%, 95% CI 0-79.3). Although individual study estimates suggested an increased risk, substantial heterogeneity between two studies done in women at high risk of HIV infection (I2 54%, 0-88.7) precluded pooling estimates. There was no evidence of an increased HIV risk in ten studies of oral contraceptive pills (pooled HR 1.00, 0.86-1.16) or five studies of norethisterone enanthate (pooled HR 1.10, 0.88-1.37).

Interpretation: Our findings show a moderate increased risk of HIV acquisition for all women using depot medroxyprogesterone acetate, with a smaller increase in risk for women in the general population. Whether the risks of HIV observed in our study would merit complete withdrawal of depot medroxyprogesterone acetate needs to be balanced against the known benefits of a highly effective contraceptive.

Abstract access

Editor’s notes: This meta-analysis has similar findings to the individual patient data (IPD) meta-analysis by Morrison et al, also published this month. The study finds that depot medroxyprogesterone (DMPA) is associated with a moderate increase in HIV risk, and little evidence of a risk associated with combined oral contraceptives or norethisterone enanthate (NET-EN). The policy implications of this finding are unclear. As with the IPD analysis, this meta-analysis is based on observational studies and does not provide conclusive evidence that DMPA causes the increased risk of HIV. However, it does provide refined estimates for modelling studies to assess the implications of possible withdrawal of DMPA on maternal and HIV-associated mortality, so that context-specific contraceptive policies can be considered.

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Incentives for orphans to stay in school: a structural programme for HIV prevention in Zimbabwe

The impact of school subsidies on HIV-related outcomes among adolescent female orphans.

Hallfors DD, Cho H, Rusakaniko S, Mapfumo J, Iritani B, Zhang L, Luseno W, Miller T. J Adolesc Health. 2015 Jan;56(1):79-84. doi: 10.1016/j.jadohealth.2014.09.004.

Purpose: We examine effects of school support as a structural HIV prevention intervention for adolescent female orphans in Zimbabwe after 5 years.

Methods: Three hundred twenty-eight orphan adolescent girls were followed in a clustered randomized controlled trial from 2007 to 2010. The experimental group received school fees, uniforms, and school supplies and were assigned a school-based "helper." In 2011-2012, the control group received delayed partial treatment of school fees only. At the final data point in 2012, survey, HIV, and Herpes Simplex Virus Type 2 (HSV-2) biomarker data were collected from approximately 88% of the sample. Bivariate and multivariate analyses were conducted on end point outcomes, controlling for age, religious affiliation, and baseline socioeconomic status.

Results: The two groups did not differ on HIV or HSV-2 biomarkers. The comprehensive 5-year intervention continued to reduce the likelihood of marriage, improve school retention, improve socioeconomic status (food security), and marginally maintain gains in quality of life, even after providing school fees to the control group.

Conclusions: Paying school fees and expenses resulted in significant improvements in life outcomes for orphan adolescent girls. Biological evidence of HIV infection prevention, however, was not observed. Our study adds to the growing body of research on school support as HIV prevention for girls in sub-Saharan Africa, but as yet, no clear picture of effectiveness has emerged.

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Editor’s notes: Structural programmes for HIV prevention potentially offer a means to mitigate the risk factors which are thought to drive the substantially higher rates of HIV observed among adolescent women in low-income settings. In Zimbabwe, female orphans in the programme arm of this randomized control trial were offered a package of school support. This included payment of their school fees. There was low power to assess differences in HIV or HSV-2 prevalence by arm, but there were promising impacts on several important mediating factors for HIV infection. These included sexual debut, marriage, school drop-out, and socioeconomic status. The long follow-up period of five years and the high rate of retention in the study, 88%, are major strengths of this study. The study joins a limited evidence base on structural programmes for adolescent women in sub-Saharan Africa. Future research must re-consider the pathways by which structural determinants of HIV infection operate.

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Optimising outcomes on second-line antiretroviral therapy: partner-based modified directly observed therapy is not the answer

Partner-based adherence intervention for second-line antiretroviral therapy (ACTG 5234): a multinational randomised trial.

Gross R, Zheng L, La Rosa A, Sun X, Rosenkrantz SL, Wagner Cardoso S, Ssali F, Camp R, Godfrey C, Cohn SE, Robbins GK, Chisada A, Wallis CL, Reynolds NR, Lu D, Safren SA, Hosey L, Severe P, Collier AC for the ACTG 5234 team. Lancet HIV 2015; 2: e12–19

Background: Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed.

Methods: We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with, number NCT00608569.

Findings: Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25·1% (95% CI 17·7–32·4) in the modified directly observed therapy group and 17·3% (10·8–23·7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of −6·6% (95% CI −16·5% to 3·2%; p=0·19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modified directly observed therapy group and n=15 in the standard-of-care group).

Interpretation: Partner-based training with modified directly observed therapy had no effect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting.

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Editor’s notes: High rates of virologic failure on second-line antiretroviral therapy (ART) are reported in resource-limited settings. The main driver of this is thought to be sub-optimal adherence rather than resistance. As many of these settings have limited access to third-line regimens there is an urgent need for evidence-informed programmes to optimise peoples’ adherence, both to first-line and second-line regimens.

The results from this randomised controlled trial provide further evidence that partner-based modified directly observed therapy is not the answer. Interestingly, people enrolled in this trial had far lower rates of virologic failure than have been observed in programmatic settings, regardless of whether they were in the programme or standard-of-care arm. Many factors could account for this, including the fact that all people enrolled in the study had to have disclosed their status to a friend or family member, all received enhanced education and support and all attended regular clinic appointments. Further pragmatic studies which focus on clinic-and patient-level programmes are needed to determine the optimal strategies for maximising peoples’ adherence. 

Africa, Latin America
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