Articles tagged as "Zambia"

Effective, long-term programmes for alcohol and sexual risk reduction are yet to be shown

HIV-alcohol risk reduction interventions in sub-Saharan Africa: a systematic review of the literature and recommendations for a way forward.

Carrasco MA, Esser MB, Sparks A, Kaufman MR. AIDS Behav. 2015 Oct 29. [Epub ahead of print]

Sub-Saharan Africa bears 69% of the global burden of HIV, and strong evidence indicates an association between alcohol consumption, HIV risk behavior, and HIV incidence. However, characteristics of efficacious HIV-alcohol risk reduction interventions are not well known. The purpose of this systematic review is to summarize the characteristics and synthesize the findings of HIV-alcohol risk reduction interventions implemented in the region and reported in peer-reviewed journals. Of 644 citations screened, 19 met the inclusion criteria for this review. A discussion of methodological challenges, research gaps, and recommendations for future interventions is included. Relatively few interventions were found, and evidence is mixed about the efficacy of HIV-alcohol risk reduction interventions. There is a need to further integrate HIV-alcohol risk reduction components into HIV prevention programming and to document results from such integration. Additionally, research on larger scale, multi-level interventions is needed to identify effective HIV-alcohol risk reduction strategies.

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Editor’s notes: Alcohol and risk of HIV have been shown to be linked, yet little is known about which programmes are best at reducing this risk. This paper features a systematic review updating a previous review published by the authors in 2011. While this update found several more programmes aimed at reducing risky behaviour caused by alcohol use and in more countries than just the one previously, South Africa, the results of the review are largely the same. Most programmes had limited follow-up time of participants and found a dissipating effect over time. Additionally, older models of behaviour change were primarily used as the frameworks upon which these programmes were built. These models focus only on individual behaviour and not on the structural factors further affecting consumption of alcohol and risky sexual behaviour. On a positive note, some studies found moderate success based on location of the programme, clinic versus bar or tavern setting for instance. This review clearly demonstrates the need for further efforts to integrate alcohol risk reduction components into HIV prevention programmes, particularly for populations in which alcohol consumption is common.

Africa
Angola, Nigeria, South Africa, Uganda, Zambia, Zimbabwe
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Which NRTI backbone is best for children?

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial.

Mulenga V, Musiime V, Kekitiinwa A, Cook AD, Abongomera G, Kenny J, Chabala C, Mirembe G, Asiimwe A, Owen-Powell E, Burger D, McIlleron H, Klein N, Chintu C, Thomason MJ, Kityo C, Walker AS, Gibb DM, CHAPAS-3 trial team. Lancet Infect Dis. 2015 Oct 5. pii: S1473-3099(15)00319-9. doi: 10.1016/S1473-3099(15)00319-9. [Epub ahead of print]

Background: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz.

Methods: In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2-4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957.

Findings: Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2.3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2.6 years vs 6.2 years in ART experienced). 917 grade 2-4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0.63; zidovudine vs stavudine: hazard ratio [HR] 0.99 [95% CI 0.75-1.29]; abacavir vs stavudine: HR 0.88 [0.67-1.15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0.58); most ART-experienced children maintained suppression (p=1.00).

Interpretation: All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines.

Abstract  Full-text [free] access

Editor’s notes: Since 2013, the World Health Organization (WHO) has recommended abacavir as the preferred first-line nucleoside reverse transcriptase inhibitor (NRTI) in children. This recommendation was largely based on expert opinion, observational studies and issues such as cost and availability as a fixed dose combinations (FDC).

The CHAPAS-3 open-label trial is the only trial in African children that has conducted a direct head-to-head comparison of the three most relevant NRTIs (abacavir, stavudine and zidovudine) used for paediatric treatment. These were co-formulated in non-NRTI/NRTI generic fixed-dose combination paediatric tablets, with dosing based on WHO drug ratios and weight bands. The other drugs in the triple regimen were lamivudine with either efavirenz or nevirapine.

The primary aim of the trial was a comparison of the toxicity profile of the three NRTIs. The trial found no major difference in any adverse event or toxicity endpoint during nearly two and a half years of follow-up in both ART-naïve and ART-experienced children. There were no hypersensitivity reactions to abacavir, in agreement with other studies that have reported its rarity in Africans. Haemoglobin increased regardless of the NRTI and severe anaemia occurred no more frequently in children who received zidovudine versus children who received either of the two other drugs. This should reassure clinicians that zidovudine substitution is rarely necessary for anaemia among children on ART. However, an important caveat is that severe anaemia was an exclusion criteria in the trial. Clinical lipodystrophy was also rare. This is in contrast to older children and adolescents where lipodystrophy is much more common. At least in young children, stavudine could be safely used if other alternatives are not available, supporting WHO guidelines that stavudine for children should not be discontinued completely.       

Overall, CHAPAS-3 demonstrates that children respond well to all NRTI/non-NRTI recommended FDCs with minimal toxicity. Unlike previous trials, there was no difference in immunological or virologic outcomes between the three drugs. Importantly, choice of the NRTI backbone should not be a barrier to widening treatment access globally for HIV-positive children. Children receiving abacavir in their first-line regimen who had unsuppressed viral load at the end of the study were less likely to have resistance mutations compromising second-line NRTIs. In addition to its excellent tolerability profile, abacavir is the only NRTI available as a once-daily FDC licenced for children. This would support WHO recommendation of abacavir as the first choice NRTI in children. However, it does remain more expensive than the other two NRTIs and further price reductions will be required if abacavir use is to be widened.

Africa
Uganda, Zambia
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AIDS and bacterial disease remain leading causes of hospital admission

Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis.

Ford N, Shubber Z, Meintjes G, Grinsztejn B, Eholie S, Mills EJ, Davies MA, Vitoria M, Penazzato M, Nsanzimana S, Frigati L, O'Brien D, Ellman T, Ajose O, Calmy A, Doherty M. Lancet HIV. 2015 Oct;2(10):e438-44. doi: 10.1016/S2352-3018(15)00137-X. Epub 2015 Aug 11.

Background: Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide.

Methods: Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age.

Findings: We obtained data from 106 cohorts, with reported causes of hospital admission for  313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children.

Interpretation: This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity.

Abstract access 

Editor’s notes: Despite the widening availability of antiretroviral therapy (ART), HIV-associated disease remains an important cause of illness and death. In this systematic review the authors summarise published data concerning causes of hospital admission among HIV-positive people since 2007. This date was selected on the basis that access to ART was limited prior to 2007.

Overall the most common causes of admission among adults, across all geographical regions, were AIDS-associated illness and bacterial infections. Tuberculosis was the most common cause among adults, accounting for 18% of all admissions, followed by bacterial pneumonia (15%). Among children, similarly AIDS-associated illnesses (particularly tuberculosis and Pneumocystis pneumonia) and bacterial infections were the most common causes of admission. Among the 20% of adults who died during their admission, the most common causes of death were tuberculosis, bacterial infections, cerebral toxoplasmosis and cryptococcal meningitis. Among children the most common causes of death were tuberculosis, bacterial infections and Pneumocystis pneumonia. Tuberculosis is likely to have been underestimated in these studies. Autopsy studies consistently illustrate that around half of HIV-positive people who have tuberculosis identified at autopsy had not been diagnosed prior to death.

The review highlights that the majority of severe HIV-associated disease remains attributable to advanced immunosuppression. This is reflected by a median CD4 count at admission among adults of 168 cells per µl. Some 30% of people first tested HIV positive at the time of the admission. The review underlines the need to promote HIV testing so that HIV-positive people can access ART, and prevent the complications of advanced HIV disease. It also underscores the need for better coverage of screening for tuberculosis and preventive therapy for people without active disease.  

Avoid TB deaths
Comorbidity, Epidemiology
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Comparing strategies for HIV testing and counselling for children and adolescents

Uptake and yield of HIV testing and counselling among children and adolescents in sub-Saharan Africa: a systematic review.

Govindasamy D, Ferrand RA, Wilmore SM, Ford N, Ahmed S, Afnan-Holmes H, Kranzer K. J Int AIDS Soc. 2015 Oct 14;18(1):20182. doi: 10.7448/IAS.18.1.20182. eCollection 2015.

Introduction: In recent years children and adolescents have emerged as a priority for HIV prevention and care services. We conducted a systematic review to investigate the acceptability, yield and prevalence of HIV testing and counselling (HTC) strategies in children and adolescents (5 to 19 years) in sub-Saharan Africa.

Methods: An electronic search was conducted in MEDLINE, EMBASE, Global Health and conference abstract databases. Studies reporting on HTC acceptability, yield and prevalence and published between January 2004 and September 2014 were included. Pooled proportions for these three outcomes were estimated using a random effects model. A quality assessment was conducted on included studies.

Results and discussion: A total of 16 380 potential citations were identified, of which 21 studies (23 entries) were included. Most studies were conducted in Kenya (n=5) and Uganda (n=5) and judged to provide moderate (n=15) to low quality (n=7) evidence, with data not disaggregated by age. Seven studies reported on provider-initiated testing and counselling (PITC), with the remainder reporting on family-centred (n=5), home-based (n=5), outreach (n=5) and school-linked HTC among primary schoolchildren (n=1). PITC among inpatients had the highest acceptability (86.3%; 95% confidence interval [CI]: 65.5 to 100%), yield (12.2%; 95% CI: 6.1 to 18.3%) and prevalence (15.4%; 95% CI: 5.0 to 25.7%). Family-centred HTC had lower acceptance compared to home-based HTC (51.7%; 95% CI: 10.4 to 92.9% vs. 84.9%; 95% CI: 74.4 to 95.4%) yet higher prevalence (8.4%; 95% CI: 3.4 to 13.5% vs. 3.0%; 95% CI: 1.0 to 4.9%). School-linked HTC showed poor acceptance and low prevalence.

Conclusions: While PITC may have high test acceptability priority should be given to evaluating strategies beyond healthcare settings (e.g. home-based HTC among families) to identify individuals earlier in their disease progression. Data on linkage to care and cost-effectiveness of HTC strategies are needed to strengthen policies.

Abstract  Full-text [free] access

Editor’s notes: In sub-Saharan Africa children and adolescents are a priority group for HIV prevention and care services. Children and adolescents living with HIV are less likely than adults to know their HIV status, to access treatment and to achieve virologic suppression. As with adults, the first essential step to managing HIV in children and adolescents is to provide appropriate HIV testing and counselling services. This is the first systematic review to assess HIV testing and counselling strategies in this age group, 5-19 years. One key finding is the lack of data on testing and counselling services for this age group. Most services replicate strategies developed for adults with little consideration for the specific needs of children and adolescents. The studies illustrated that health care facility-based provider-initiated testing and counselling had relatively high acceptance, yield and linkage-to-care, but tended to identify individuals at a late stage of disease. In contrast, community-based approaches had the potential to diagnose asymptomatic children. Further work on innovative approaches, family-centred and mobile-based, should be assessed.  

HIV testing
Africa
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Invasive cervical cancer and HIV – young women need access to screening

Implementation and operational research: age distribution and determinants of invasive cervical cancer in a "screen-and-treat" program integrated with HIV/AIDS care in Zambia.

Kapambwe S, Sahasrabuddhe VV, Blevins M, Mwanahamuntu MH, Mudenda V, Shepherd BE, Chibwesha CJ, Pfaendler KS, Hicks ML, Vermund SH, Stringer JS, Parham GP. J Acquir Immune Defic Syndr. 2015 Sep 1;70(1):e20-6. doi: 10.1097/QAI.0000000000000685.

Background: Cervical cancer screening efforts linked to HIV/AIDS care programs are being expanded across sub-Saharan Africa. Evidence on the age distribution and determinants of invasive cervical cancer (ICC) cases detected in such programs is limited.

Methods: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia, the largest public sector programs of its kind in sub-Saharan Africa. We examined age distribution patterns by HIV serostatus of histologically confirmed ICC cases and used multivariable logistic regression to evaluate independent risk factors for ICC among younger (≤35 years) and older (>35 years) women.

Results: Between January 2006 and April 2010, of 48 626 women undergoing screening, 571 (1.2%) were diagnosed with ICC, including 262 (46%) HIV seropositive (median age: 35 years), 131 (23%) HIV seronegative (median age: 40 years), and 178 (31%) of unknown HIV serostatus (median age: 38 years). Among younger (≤35 years) women, being HIV seropositive was associated with a 4-fold higher risk of ICC [adjusted odds ratio = 4.1 (95% confidence interval: 2.8, 5.9)] than being HIV seronegative. The risk of ICC increased with increasing age among HIV-seronegative women and women with unknown HIV serostatus, but among HIV-seropositive women, the risk peaked around age 35 and nonsignificantly declined with increasing ages. Other factors related to ICC included being married (vs. being unmarried/widowed) in both younger and older women, and with having 2+ (vs. ≤1) lifetime sexual partners among younger women.

Conclusions: HIV infection seems to have increased the risk of cervical cancer among younger women in Zambia, pointing to the urgent need for expanding targeted screening interventions.

Abstract access 

Editor’s notes: Increasingly, HIV care services (includes AIDS) are providing platforms for introduction of cervical cancer screening programmes in sub-Saharan Africa. Screening is often also available for HIV-negative women. This analysis of data from a large routine programme gives a useful indication of the rates of identification of invasive cervical cancer (ICC), and describes the burden and distribution of disease; information relevant to future service provision. The association described of ICC with HIV and sexual behaviour is well-known. The findings highlight the importance of ensuring that younger women (especially if known to be HIV-positive) have access to routine screening. A significant part of the burden is borne by older women. HIV status may not always be known or revealed. Important questions remain concerning the cost-benefit of providing screening services and the effect of ART on risk of ICC. In addition, the potential role of human papilloma virus vaccine, which GAVI is currently implementing in demonstration projects in the region, in influencing the risk of ICC in younger women remains to be determined. 

Avoid TB deaths
Cancers, HIV
Africa
Zambia
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HIV-associated stigma may impede HIV medication adherence among people living with HIV

The association of HIV-related stigma to HIV medication adherence: a systematic review and synthesis of the literature.

Sweeney SM, Vanable PA. AIDS Behav. 2015 Aug 25. [Epub ahead of print]

This paper provides a review of the quantitative literature on HIV-related stigma and medication adherence, including: (1) synthesis of the empirical evidence linking stigma to adherence, (2) examination of proposed causal mechanisms of the stigma and adherence relationship, and (3) methodological critique and guidance for future research. We reviewed 38 studies reporting either cross-sectional or prospective analyses of the association of HIV-related stigma to medication adherence since the introduction of antiretroviral therapies (ART). Although there is substantial empirical evidence linking stigma to adherence difficulties, few studies provided data on psychosocial mechanisms that may account for this relationship. Proposed mechanisms include: (a) enhanced vulnerability to mental health difficulties, (b) reduction in self-efficacy, and (c) concerns about inadvertent disclosure of HIV status. Future research should strive to assess the multiple domains of stigma, use standardized measures of adherence, and include prospective analyses to test mediating variables.

Abstract access 

Editor’s notes: People living with HIV often experience stigma and discrimination including social isolation and negative stereotyping. Recent evidence suggests that stigma may influence adherence to HIV medication among people living with HIV. This paper presents findings from a systematic review of the evidence on the impact of HIV-associated stigma on HIV medication adherence. The authors identified 38 studies which quantitatively assessed the association between stigma and medication adherence. All studies found evidence indicating that stigma contributed to adherence difficulties among people living with HIV. Included studies looked at diverse patient populations sampled from different countries and contexts. While stigma is heavily influenced by the socio-cultural context, the association between stigma and adherence across diverse contexts indicates that there may be commonalities in what causes stigma and how this relates to adherence.

The authors of this review suggest three possible causal mechanisms of HIV-associated stigma and medication adherence: (1) There may be links between stigma and depressive symptoms, and between depressive symptoms and adherence. Internalized stigma may enhance vulnerability to depressive symptoms, and this may influence adherence to HIV medication. (2) Stigma may cause reductions in self-efficacy – a person’s judgment of his or her ability to organize and execute behaviours - which may influence medication adherence. (3) People may fear HIV status disclosure by being seen taking HIV medication. Fear of status disclosure, and associated stigma, may cause people to avoid taking HIV medication.

The studies included in this review indicate a clear link between HIV-associated stigma and HIV medication adherence. There may be commonalities in what causes stigma across multiple populations. Future research should assess the influence of multiple forms of stigma on adherence, and on testing causal mechanisms between stigma and adherence. 

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Benefits to women and newborns by integrating HIV and ANC services

Integration of PMTCT and antenatal services improves combination antiretroviral therapy (cART) uptake for HIV-positive pregnant women in Southern Zambia - a prototype for option B+?

Herlihy JM, Hamomba L, Bonawitz R, Goggin CE, Sambambi K, Mwale J, Musonda V, Musokatwane K, Hopkins KL, Semrau K, Hammond EE, Duncan J, Knapp AB, Thea DM. J Acquir Immune Defic Syndr. 2015 Jul 15. [Epub ahead of print]

Background: Early initiation of combination anti-retroviral therapy (cART) for HIV-positive pregnant women can decrease vertical transmission to less than 5%. Programmatic barriers to early cART include decentralized care, disease stage assessment delays, and loss-to-follow-up.

Intervention: Our intervention had 3 components: integrated HIV and antenatal services in one location with one provider; lab courier to expedite CD4 counts; and community-based follow-up of women-infant pairs to improve PMTCT attendance. Pre-intervention HIV-positive pregnant women were referred to HIV clinics for disease stage assessment and cART initiation for advanced disease CD4< 350 or WHO stage >2.

Methods: We employed a quasi-experimental design with pre/post-intervention evaluations at 6 government antenatal clinics (ANC) in Southern Province, Zambia. Retrospective clinical data were collected from clinic registers during a 7-month baseline period. Post-intervention data were collected from all ART-naive, HIV-positive pregnant women and their infants presenting to ANC from December 2011-June 2013.

Results: Data from 510 baseline women-infant pairs were analyzed and 624 pregnant women were enrolled during the intervention period. Proportion of HIV-positive pregnant women receiving CD4 counts increased from 50.6% to 77.2%, RR=1.81 95% CI: 1.57-2.08; p<0.01. Proportion of cART-eligible pregnant women initiated on cART increased from 27.5% to 71.5% RR=2.25, 95% CI: 1.78-2.83; p<0.01. Proportion of eligible HIV-exposed infants with documented 6-week HIV PCR test increased from 41.9% to 55.8%, RR=1.33, 95% CI: 1.18-1.51; p<0.01.

Conclusion: Integration of HIV care into ANC and community-based support improved uptake of CD4 counts, proportion of cART-eligible women initiated on cART and infants tested.

Abstract access 

Editor’s notes: Integrating HIV services into other elements of health care, such as family planning or maternal health services, can increase uptake of HIV testing and antiretroviral therapy (ART) initiation. For pregnant women, timely HIV diagnosis and treatment can greatly reduce the probability of mother-to-child transmission. Integrating HIV services into maternal antenatal clinic (ANC) services therefore has potential to bring benefit to women living with HIV and their newborns. This paper describes an experimental study in which six ANC clinics in Zambia – all with high attendance and in provinces with high HIV prevalence – integrated HIV testing and treatment into their routine ANC services. This integration took the form of training existing ANC providers in HIV diagnosis and management; providing a rapid CD4 measurement service; and training volunteer lay counsellors to maintain regular contact with mothers living with HIV to improve ART initiation and adherence. The programme was associated with dramatic increases in ART initiation, early testing of infants and early ART initiation. The integrated approach used here has potential to improve prevention of mother-to-child transmission services. This is done through streamlined combination antiretroviral therapy (cART) initiation and decreasing time gaps in referral models. The approach assists in reducing HIV associated stigma and fear as the clinics offer maternal/child health services as well as HIV care. The clinics offer continuity through a community lay counsellor who follows the mother infant pair through pregnancy, delivery and breastfeeding. Further work is necessary to evaluate strategies for HIV care retention through similar models using community health workers and family-centric HIV care.

Africa
Zambia
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Switching to second-line ART – we need to do better

Monitoring and switching of first-line antiretroviral therapy in sub-Saharan Africa: collaborative analysis of adult treatment cohorts.

Haas AD, Keiser O, Balestre E, Brown S, Bissagnene E, Chimbetete C, Dabis F, Davies MA, Hoffmann CJ, Oyaro P, Parkes-Ratanshi R, Reynolds SJ, Sikazwe I, Wools-Kaloustian K, Zannou DM, Wandeler G, Egger M, for IeDea Southern Africa EA, West A. Lancet HIV. 2015 Jul 1;2(7):e271-e278.

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297 825 eligible patients, 10 352 (3%) switched to second-line ART during 782 412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine viral load monitoring, 1·21 (1·13–1·30) for targeted viral load monitoring, and 0·49 (0·43–0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5–59·6) switched by 2 years, and of 15 892 patients with confirmed immunological failure, 19·3% (18·5–20·0) switched by 2 years. Of 10 352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117–335) with routine viral load monitoring, but were lower with other types of monitoring (range 114–133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Abstract access 

Editor’s notes: Routine viral load monitoring should allow the early identification of first-line antiretroviral therapy (ART) failure, allowing prompt switch to second-line ART. Prolongation of treatment with a failing regimen compromises future therapeutic options (through the accumulation of drug resistance mutations) and potentially leads to increased morbidity and mortality. Previous reports from Africa have suggested that surprisingly few people switch to second-line therapy, even in programmes with routine viral load monitoring. This raises concerns that there are challenges on the ground with identification and management of ART failure.

This is a comprehensive analysis bringing together data from a number of well-characterised cohorts in Africa. In this analysis, switching to second-line ART was rare (3% over an average of almost three years follow-up). In programmes with routine viral load monitoring, only half of the people with confirmed virologic failure on first-line ART (two viral loads >1000 copies/ml) were recorded as having been switched to second-line ART. Furthermore, half of the people that were switched to a second-line regimen did not have evidence of confirmed virologic failure, suggesting that some may have been switched too early without first attempting adherence programmes which may achieve re-suppression on first-line ART. Unsurprisingly, rates of switching were lower in programmes with CD4+ monitoring (with or without targeted viral load testing) or clinical monitoring alone. 

While guidelines and algorithms around identification and management of first-line ART failure are relatively clear and straightforward, translating this into action on the ground seems to be difficult. At least part of this is likely to be due to the lack of tools to reliably measure adherence and the consequent difficulty that frontline health care workers have in identifying people that truly require a switch to second-line ART. Moreover, most programmes still do not routinely monitor indicators relating to virologic suppression or treatment failure and so this might not be seen as a priority by health care workers and programme managers. There is a need for research to explore how best to maximise virologic suppression in resource-constrained settings, as well as studies to evaluate the impact of programmes such as point-of-care viral load testing.

Africa
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Sexual risk reduction and behavioural programme increases uptake of circumcision in hard-to-reach men

A cluster randomized controlled trial to increase the availability and acceptability of voluntary medical male circumcision in Zambia: the Spear and Shield Project.

Weiss SM, Zulu R, Jones DL, Redding CA, Cook R, Chitalu N. Lancet HIV. 2015 May 1;2(5):e181-e189.

Background: Widespread voluntary medical male circumcision in Africa could avert an estimated 3.436 million HIV infections and 300 000 deaths over the next 10 years. Most Zambian men have expressed little interest in the procedure. We tested the effect of the Spear and Shield intervention designed to increase demand for voluntary medical male circumcision among these hard-to-reach men.

Methods: This cluster randomised controlled trial was done between Feb 1, 2012, and Oct 31, 2014, in Lusaka, Zambia, where HIV prevalence is 20.8%. 13 community health centres were stratified by HIV voluntary counselling and testing rates and patient census, and randomly assigned (5:5:3) to experimental (the intervention), control, or observation-only conditions. Community health centre health-care providers at all 13 sites received training in voluntary medical male circumcision. Eligible participants were aged at least 18 years, HIV-negative, uncircumcised, and had not proactively requested or planned for voluntary medical male circumcision at the time of enrolment. Trial statisticians did not participate in randomisation. After voluntary counselling and HIV testing, participants were recruited; female partners were invited to participate. The primary outcomes at the individual level were the likelihood of voluntary medical male circumcision by 12 months post intervention, and condom use after voluntary medical male circumcision among participants receiving the intervention. The trial is registered with ClinicalTrials.gov, number NCT01688167.

Findings: 800 uncircumcised HIV-negative men (400 in the experimental group, 400 in the control group) were enrolled. 161 participants in the experimental group and 96 in the control group had voluntary medical male circumcision (adjusted odds ratio 2.45, 95% CI 1.24–4.90; p=0.02). Condom use was examined in participants who had voluntary medical male circumcision and reported sexual activity within 1 month of a post-circumcision assessment (88 in the experimental group and 64 in the control group). Condom use over time increased in the experimental group (p=0.03) but not in the control group (p=0.2). One patient died in each group; no adverse events related to study participation were reported.

Interpretation: Comprehensive HIV prevention programmes can increase the demand for and uptake of voluntary medical male circumcision services.

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Editor’s notes: Voluntary medical male circumcision reduces the risk of HIV acquisition in men by approximately 60%, yet in some high-prevalence countries uptake is low. This presents challenges in meeting WHO targets of 80% coverage. In Zambia, only 37% of the national target has been achieved. In this cluster randomised trial, 13 community health centres were randomised to receive training in the “Spear and Shield” programme, control (training for an equivalent period of time on general disease prevention strategies) or observation only. The Spear and Shield programme consisted of four weekly 90 minute group sessions. Men in the programme group had about 2.5 times the odds of having male circumcision, compared to the control group participants. This increase in uptake of male circumcision was not associated with an increase in sexual risk behaviours. In fact there was an increase in condom use in the programme group. According to WHO, demand creation continues to be the major challenge in meeting male circumcision coverage goals. The authors propose that scaling up an evidence-informed programme such as Spear and Shield, while training community health care workers to perform circumcisions, might be one of the best and most cost-effective ways to significantly reduce HIV rates in high-incidence settings.

Africa
Zambia
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Where are the weak links in prevention of mother-to-child HIV transmission programmes?

Reconstructing the PMTCT cascade using cross-sectional household survey data: The PEARL Study.

Chi BH, Tih PM, Zanolini A, Stinson K, Ekouevi DK, Coetzee D, Welty TK, Bweupe M, Shaffer N, Dabis F, Stringer EM, Stringer JS. J Acquir Immune Defic Syndr. 2015 Jun 11. [Epub ahead of print]

Background: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity.

Methods: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past two years. Among mothers confirmed to be HIV-infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed via DNA PCR.

Results: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95%CI: 7%-12%).

Conclusions: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL Study - including HIV testing of HIV-exposed children in household surveys - to better understand program effectiveness.

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Editor’s notes: Programmes to prevent the transmission of HIV from mother-to-child can virtually eliminate transmission when conducted with adequate coverage and quality. This population-based study recruited women living with HIV who had given birth in the past 24 months from four sub-Saharan African countries including Cameroon, Côte d’Ivoire, South Africa and Zambia. The 976 mothers allowed their children to be tested for HIV, and reported on the level of maternal health services they received for that child, the “prevention of mother-to-child HIV transmission cascade”. While 98% of mothers had at least one contact with antenatal care services, only 36% eventually received services considered to be adequate for preventing transmission of HIV to their children. This study is notable for highlighting exactly where coverage gaps exist along the treatment pathway. In particular, 53% of mothers did not receive the result of an HIV test, and so would not have received follow-up services to prevent transmission. As a population-based study, these data provide a fuller picture of service coverage which cannot be captured by traditional monitoring and evaluations systems. These results can inform where systems strengthening must occur along the “prevention of mother-to-child HIV transmission cascade”, so that transmission risk is minimized for all children born to women living with HIV.

Africa
Cameroon, Côte d'Ivoire, South Africa, Zambia
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