Articles tagged as "Preventing HIV infection in children"

“Cure” of HIV in a baby?

Absence of Detectable HIV-1 Viremia after Treatment Cessation in an Infant.

Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M, Chun TW, Strain M, Richman D, Luzuriaga K. N Engl J Med. 2013 Oct 23. [Epub ahead of print]

An infant born to a woman with human immunodeficiency virus type 1 (HIV-1) infection began receiving antiretroviral therapy (ART) 30 hours after birth owing to high-risk exposure. ART was continued when detection of HIV-1 DNA and RNA on repeat testing met the standard diagnostic criteria for infection. After therapy was discontinued (when the child was 18 months of age), levels of plasma HIV-1 RNA, proviral DNA in peripheral-blood mononuclear cells, and HIV-1 antibodies, as assessed by means of clinical assays, remained undetectable in the child through 30 months of age. This case suggests that very early ART in infants may alter the establishment and long-term persistence of HIV-1 infection.

Abstract access

Editor’s notes: This case report received wide media attention when it was presented at the Conference for Retroviruses and Opportunistic Infections in March 2013. A child, born to a mother with untreated HIV disease at the time of delivery, received combination antiretroviral therapy (ART) starting 30 hours after birth. ART was discontinued in an unplanned interruption at 18 months. When the child returned to care, the HIV viral load was undetectable, and has remained so to 36 months without re-initiation of treatment. The authors argue that the detectable viral load in the child at birth was unlikely to be due to transfusion of the mother’s blood to the child during labour. Also, that the child likely acquired HIV prior to the onset of labour, so ART was unlikely to have acted as post exposure prophylaxis. Although some of the tests for residual infection have been equivocal, the fact that the HIV viral load has not rebounded after treatment was discontinued suggests that HIV reservoirs were either not established or were abated. 

Since this is a case report with no comparator group, it remains uncertain to what degree early ART initiation influenced the outcome in this child. However, the observation that, 18 months after discontinuing ART, this child has an undetectable viral load raises the possibility that ART initiation very early after infection could profoundly alter the course of HIV infection.

Northern America
United States of America
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Intrauterine infections, but not obstetric complications, more common among pregnant women with HIV

HIV and the Risk of Direct Obstetric Complications: A Systematic Review and Meta-Analysis. 

Calvert C, Ronsmans C. PLoS One. 2013 Oct 4;8(10):e74848. doi:10.1371/journal.pone.0074848.

Background: Women of reproductive age in parts of sub-Saharan Africa are faced both with high levels of HIV and the threat of dying from the direct complications of pregnancy. Clinicians practicing in such settings have reported a high incidence of direct obstetric complications among HIV-infected women, but the evidence supporting this is unclear. The aim of this systematic review is to establish whether HIV-infected women are at increased risk of direct obstetric complications.

Methods and findings: Studies comparing the frequency of obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia and intrauterine infections in HIV-infected and uninfected women were identified. Summary estimates of the odds ratio (OR) for the association between HIV and each obstetric complication were calculated through meta-analyses. In total, 44 studies were included providing 66 data sets; 17 on haemorrhage, 19 on hypertensive disorders, five on dystocia and 25 on intrauterine infections. Meta-analysis of the OR from studies including vaginal deliveries indicated that HIV-infected women had over three times the risk of a puerperal sepsis compared with HIV-uninfected women [pooled OR: 3.43, 95% confidence interval (CI): 2.00-5.85]; this figure increased to nearly six amongst studies only including women who delivered by caesarean (pooled OR: 5.81, 95% CI: 2.42-13.97). For other obstetric complications the evidence was weak and inconsistent.

Conclusions: The higher risk of intrauterine infections in HIV-infected pregnant and postpartum women may require targeted strategies involving the prophylactic use of antibiotics during labour. However, as the huge excess of pregnancy-related mortality in HIV-infected women is unlikely to be due to a higher risk of direct obstetric complications, reducing this mortality will require non obstetric interventions involving access to ART in both pregnant and non-pregnant women.

Abstract  Full-text [free] access

Editor’s notes: Women with HIV are thought to have a higher risk of adverse outcomes during pregnancy. This review is valuable in summarizing available data on this topic. Many of the included studies predated the wide availability of antiretroviral therapy. There was a clear association between HIV infection and intrauterine infections, but not with the other obstetric complications, e.g., obstetric haemorrhage, hypertensive disorders of pregnancy, dystocia, examined in the review. Considering individual conditions analysed, HIV infection was associated with antepartum haemorrhage, (but not postpartum haemorrhage). It was also found to be associated with pregnancy-induced hypertension (but not pre-eclampsia or eclampsia), and uterine rupture or prolonged labour (but not other complications of dystocia). The authors note that the studies were generally of low quality, and there were too few studies to examine the effect of antiretroviral therapy on these complications.  

Given the excess of intrauterine infections in women with HIV, the authors suggest that these might be preventable with prophylactic antibiotics. Overall, where causes of maternal mortality are documented, pregnant women with HIV are more likely to die of non-pregnancy related infections, than of obstetric complications. Specifically, non-pregnancy related infections are tuberculosis, pneumonia or meningitis. Pregnant women living with HIV need access to antenatal services and a skilled attendant at delivery. But, the top priority with respect to reducing maternal mortality is effective antiretroviral therapy.

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Evidence lacking to guide timing of ART start for children aged 2-5 years

Optimal time for initiating antiretroviral therapy (ART) in HIV-infected, treatment-naive children aged 2 to 5 years old.

Siegfried N, Davies MA, Penazzato M, Muhe LM, Egger M. Cochrane Database Syst Rev. 2013 Oct 10;10:CD010309. [Epub ahead of print]

Background: The use of combination antiretroviral therapy (cART) comprising three antiretroviral medications from at least two classes of drugs is the current standard treatment for HIV infection in adults and children. Current World Health Organization (WHO) guidelines for antiretroviral therapy recommend early treatment regardless of immunologic thresholds or the clinical condition for all infants (less than one years of age) and children under the age of two years. For children aged two to five years current WHO guidelines recommend (based on low quality evidence) that clinical and immunological thresholds be used to identify those who need to start cART (advanced clinical stage or CD4 counts ≤ 750 cells/mm3 or per cent CD4 ≤ 25%). This Cochrane review will inform the current available evidence regarding the optimal time for treatment initiation in children aged two to five years with the goal of informing the revision of WHO 2013 recommendations on when to initiate cART in children.

Objectives: To assess the evidence for the optimal time to initiate cART in treatment-naive, HIV-infected children aged 2 to 5 years.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the AEGIS conference database, specific relevant conferences, www.clinicaltrials.gov, the World Health Organization International Clinical Trials Registry platform and reference lists of articles. The date of the most recent search was 30 September 2012.

Selection criteria: Randomised controlled trials (RCTs) that compared immediate with deferred initiation of cART, and prospective cohort studies which followed children from enrolment to start of cART and on cART.

Data collection and analysis: Two review authors considered studies for inclusion in the review, assessed the risk of bias, and extracted data on the primary outcome of death from all causes and several secondary outcomes, including incidence of CDC category C and B clinical events and per cent CD4 cells (CD4%) at study end. For RCTs we calculated relative risks (RR) or mean differences with 95% confidence intervals (95% CI). For cohort data, we extracted relative risks with 95% CI from adjusted analyses. We combined results from RCTs using a random effects model and examined statistical heterogeneity.

Main results: Two RCTs in HIV-positive children aged 1 to 12 years were identified. One trial was the pilot study for the larger second trial and both compared initiation of cART regardless of clinical-immunological conditions with deferred initiation until per cent CD4 dropped to <15%. The two trials were conducted in Thailand, and Thailand and Cambodia, respectively. Unpublished analyses of the 122 children enrolled at ages 2 to 5 years were included in this review. There was one death in the immediate cART group and no deaths in the deferred group (RR 2.9; 95% CI 0.12 to 68.9). In the subgroup analysis of children aged 24 to 59 months, there was one CDC C event in each group (RR 0.96; 95% CI 0.06 to 14.87) and 8 and 11 CDC B events in the immediate and deferred groups respectively (RR 0.95; 95% CI 0.24 to 3.73). In this subgroup, the mean difference in CD4 per cent at study end was 5.9% (95% CI 2.7 to 9.1). One cohort study from South Africa, which compared the effect of delaying cART for up to 60 days in 573 HIV-positive children starting tuberculosis treatment (median age 3.5 years), was also included. The adjusted hazard ratios for the effect on mortality of delaying ART for more than 60 days was 1.32 (95% CI 0.55 to 3.16).

Authors' conclusions: This systematic review shows that there is insufficient evidence from clinical trials in support of either early or CD4-guided initiation of ART in HIV-infected children aged 2 to 5 years. Programmatic issues such as the retention in care of children in ART programmes in resource-limited settings will need to be considered when formulating WHO 2013 recommendations. 

Abstract   Full-text [free] access

Editor’s notes: Immediate treatment of HIV infection with antiretroviral therapy (ART), i.e., regardless of immunological thresholds, is recommended for infants and children up to two years of age.  This recommendation followed the findings of the children with HIV early antiretroviral (CHER) trial. The CHER trial showed significantly lower mortality in infants who received immediate ART compared to those who received deferred ART (i.e. ART started only when they met immunological and/or clinical criteria).

This Cochrane review sought to investigate the optimal timing for ART start in the 2-5 year age-group to inform development of the WHO 2013 HIV treatment guidelines. The review included two trials: one was a pilot study for the main trial, and the main trial itself. This included a broader age-group of one to twelve years, and a post-hoc sub-group analysis was required for the 2-5 year age-group. The sample size was small, and there were very few outcome events. The one cohort study included in the review had similar limitations and had a very short follow-up period. Overall, no significant difference was found in mortality or in numbers of clinical events between children who received immediate versus deferred ART.

It is not possible to draw conclusions about the clinical impact of immediate versus deferred ART from these studies. The long term beneficial or adverse effects of ART in this age-group are also not clear. Retention in care and adherence to ART are particularly problematic in this age-group and may countermand any clinical benefits, if they exist. There remains equipoise and trials are needed to address the optimal timing of ART initiation for older children. 

Africa, Asia
Cambodia, South Africa, Thailand
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Taking services to the community: the effective provision of TB, HIV and vertical HIV prevention services by community care workers

Community-based intervention to enhance provision of integrated TB-HIV and PMTCT services in South Africa.

Uwimana J, Zarowsky C, Hausler H, Swanevelder S, Tabana H, Jackson D. . Int J Tuberc Lung Dis. 2013 Oct;17(10 Suppl 1):48-55.doi: 10.5588/ijtld.13.0173.

Objective: To conduct an impact assessment of an intervention to enhance the provision of community-based integrated services for tuberculosis (TB), human immunodeficiency virus (HIV) and prevention of mother-to-child transmission (PMTCT).

Methods: The intervention consisted of a combination of training of community care workers (CCWs), structural adjustments, harmonisation of scope of practice and stipend of CCWs and enhanced supervision of CCWs to provide comprehensive TB-HIV/PMTCT services in a rural South African district. A before and after study design was used with a household survey to assess the operational effectiveness of the intervention. Six clusters were randomised into intervention and control arms. Quantitative data were analysed using logistic regression, adjusting for cluster design.

Results: Logistic regression analyses of the survey data show that CCWs from the intervention arm performed better in the provision of TB-HIV/PMTCT services, such as screening for TB and sexually transmitted infections, adherence to anti-tuberculosis treatment and antiretroviral therapy and counselling on infant feeding compared to the control CCWs (P < 0.05). However, intervention CCWs performed worse in the integrated management of childhood illnesses education and social welfare referrals (P < 0.05). The uptake of HIV testing increased significantly in the intervention arm, from 55% to 78% (P < 0.001).

Conclusion: The intervention was effective in enhancing the provision of community-based TB-HIV and PMTCT services. However, attention to other primary health care services is required to ensure that all key services are provided.

Abstract  Full-text [free] access 

Editor’s notes: Community care workers (CCWs) have the potential to expand primary health care beyond health facilities. However, in many settings where integrated TB-HIV services have mainly been promoted at facility level, there is little engagement of communities and community care workers. This is inefficient, and can lead to fragmented services. This clustered, before after study, assessed the impact of an intervention that trained/upskilled CCWs to provide comprehensive TB-HIV/vertical HIV prevention services. The intervention integrated CCWs into one cadre, established a facility-community linkage, harmonized the scope of practice of CCWs and improved CCW supervision. The findings are very positive, suggesting that the intervention increased the coverage of TB-HIV/STI case finding, infant feeding counselling and antiretroviral treatment adherence support, and improved anti-tuberculosis treatment adherence and outcomes. However, other outcomes were more mixed: with less education on the integrated management of childhood illnesses, referral for vital documents and referral for social grants, performance was worse; but there was improved referral for weighing and immunization. The findings highlight the feasibility and effectiveness of community-based integrated TB-HIV/PMTCT services provision, and the need to ensure that other outcomes are not adversely affected.  

Africa
South Africa
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LPV/r mono-therapy: a future option for preventing mother to child transmission?

Lopinavir/Ritonavir monotherapy as a nucleoside analogue-sparing strategy to prevent HIV-1 mother-to-child transmission: The ANRS 135 PRIMEVA phase 2/3 randomized trial.

Tubiana R, Mandelbrot L, Le Chenadec J, Delmas S, Rouzioux C, Hirt D, Treluyer JM, Ekoukou D, Bui E, Chaix ML, Blanche S, Warszawski J; ANRS 135 PRIMEVA (Protease Inhibitor Monotherapy Evaluation)Study Group. Clin Infect Dis. 2013 Sep;57(6):891-902. doi: 10.1093/cid/cit390. Epub 2013 Jun 12.

Background:  Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1-infected women not requiring antiretrovirals for themselves could control maternal viral load (VL).

Methods:  Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/µL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance.

Results:  Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL <200 copies/mL at 34 weeks' gestation (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%-95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper limit = 5.2%).

Conclusions:  LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof of concept for future nucleoside-sparing strategies.

Clinical Trials Registration. NCT00424814; Afssaps AIDS Clinical Trial Group A61176-34.

Abstract access 

Editor’s notes: Treating pregnant mothers with antiretroviral therapy (ART) is an effective strategy for eliminating new HIV infections in children. Currently recommended regimens comprise two nucleoside reverse transcriptase inhibitors (NRTIs) and either a ritonavir boosted protease inhibitor or non-nucleoside reverse transcriptase inhibitor (NNRTI). However, as NRTIs’ can cross the placenta and have a natural affinity for mitochondrial and nuclear human DNA, concerns have been raised that children exposed to NRTIs in-utero are at risk of long-term toxicity. In this ‘proof-of-concept’ randomized controlled trial (RCT) the researchers compared a NRTI-sparing regimen (ritonavir boosted lopinavir [LPV/r] mono-therapy) to standard of care (2 NRTIs plus LPV/r) in pregnant women who did not require ART for their own health. Mono-therapy was found to have satisfactory virological efficacy in terms of the primary end-point, maternal viral load (VL) <200 copies/ml at 8 weeks; however these women were more likely to have low level viraemia at birth (78.3% versus 97.2% with VL<50 copies/ml [p=0.01] with only one woman on mono-therapy having VL >400 copies/ml). As the authors state, the implications of low level maternal viraemia at birth are uncertain, with the targets set in national guidelines varying between 1000 copies/ml in USA to 50 copies/ml in UK. These results indicate that NRTI-sparing regimens, such as protease inhibitor (PI) mono-therapy, may be an alternative strategy for preventing mother to child transmission in an immune-competent woman with low viral loads in high-income settings. However, as this strategy requires serial VL monitoring, PI mono-therapy is unlikely to be a viable option for many low- and middle income countries. 

Europe
France
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High prevalence of primary resistance in HIV-infected pregnant women

HIV-1 drug resistance in recently HIV-infected pregnant mother's naive to antiretroviral therapy in Dodoma urban, Tanzania.

Vairo F, Nicastri E, Liuzzi G, Chaula Z, Nguhuni B, Bevilacqua N, Forbici F, Amendola A, Fabeni L, De Nardo P, Perno CF, Cannas A, Sakhoo C, Capobianchi MR, Ippolito G. BMC Infect Dis. 2013 Sep 21;13(1):439. [Epub ahead of print]

Background: HIV resistance affects virological response to therapy and efficacy of prophylaxis in mother-to-child-transmission. The study aims to assess the prevalence of HIV primary resistance in pregnant women naive to antiretrovirals.

Methods: Cross sectional baseline analysis of a cohort of HIV + pregnant women (HPW) enrolled in the study entitled Antiretroviral Management of Antenatal and Natal HIV Infection (AMANI, peace in Kiswahili language). The AMANI study began in May 2010 in Dodoma, Tanzania. In this observational cohort, antiretroviral treatment was provided to all women from the 28th week of gestation until the end of the breastfeeding period. Baseline CD4 cell count, viral load and HIV drug-resistance genotype were collected.

Results: Drug-resistance analysis was performed on 97 naive infected-mothers. The prevalence of all primary drug resistance and primary non-nucleoside reverse-transcriptase inhibitors resistance was 11.9% and 7.5%, respectively. K103S was found in two women with no M184V detection. HIV-1 subtype A was the most commonly identified, with a high prevalence of subtype A1, followed by C, D, C/D recombinant, A/C recombinant and A/D recombinant. HIV drug- resistance mutations were detected in A1 and C subtypes.

Conclusion: Our study reports an 11.9% prevalence of primary drug resistance in naive HIV-infected pregnant women from a remote area of Tanzania. Considering that the non-nucleoside reverse-transcriptase inhibitors are part of the first-line antiretroviral regimen in Tanzania and all of Africa, resistance surveys should be prioritized in settings where antiretroviral therapy programs are scaled up.

Abstract Full-text [free] access

Editor’s notes: This nested cross-sectional study of HIV-positive pregnant women in a rural area of Tanzania found a high prevalence of HIV-1 drug resistance. To be eligible for inclusion in this study, patients had to have been diagnosed with HIV during their current pregnancy and have had no prior exposure to antiretroviral therapy (including single dose nevirapine). Thus, transmitted drug resistance is a more likely explanation than acquired drug resistance. These findings, which are consistent with other reports from the region, raise concerns about the future use of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens in the region, whether this is for preventing mother to child transmission or as a recommended first-line regimen.

Africa
United Republic of Tanzania
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Adolescent mothers are not linking to care

HIV-Infected adolescent mothers and their infants: low coverage of HIV services and high risk of HIV transmission in KwaZulu-Natal, South Africa.  

Horwood C, Butler LM, Haskins L, Phakathi S, Rollins N. PLoS One. 2013 Sep 20;8(9):e74568. doi: 10.1371/journal.pone.0074568.

Objectives: Rates of pregnancy and HIV infection are high among South African adolescents, yet little is known about rates of mother-to-child transmission of HIV (MTCT) in this group. We report a comparison of the characteristics of adolescent mothers and adult mothers, including HIV prevalence and MTCT rates.

Methods: We examined patterns of health service utilization during the antenatal and early postnatal period, HIV prevalence and MTCT amongst adolescent (20-years-old) and adult (20 to 39-years-old) mothers with infants aged 16 weeks attending immunization clinics in six districts of KwaZulu-Natal between May 2008 and April 2009.

Findings: Interviews were conducted with 19 093 mothers aged between 12 and 39 years whose infants were aged 16 weeks. Most mothers had attended antenatal care four or more times during their last pregnancy (80.3%), and reported having an HIV test (98.2%). A greater proportion of HIV-infected adult mothers, compared to adolescent mothers, reported themselves as HIV-positive (41.2% vs. 15.9%, p,0.0001), reported having a CD4 count taken during their pregnancy (81.0% vs. 66.5%, p,0.0001), and having received the CD4 count result (84.4% vs. 75.7%, p,0.0001). Significantly fewer adolescent mothers received the recommended PMTCT regimen. HIV antibody was detected in 40.4% of 7 800 infants aged 4–8 weeks tested for HIV, indicating HIV exposure. This was higher among infants of adult mothers (47.4%) compared to adolescent mothers (17.9%, p,0.0001). The MTCT rate at 4–8 weeks of age was significantly higher amongst infants of adolescent mothers compared to adult mothers (35/325 [10.8%] vs. 185/2,800 [6.1%], OR 1.7, 95% CI 1.2–2.4).

Conclusion: Despite high levels of antenatal clinic attendance among pregnant adolescents in KwaZulu-Natal, the MTCT risk is higher among infants of HIV-infected adolescent mothers compared to adult mothers. Access to adolescent-friendly family planning and PMTCT services should be prioritised for this vulnerable group.

Abstract  Full-text [free] access

Editorial notes:   Adolescents have high pregnancy rates in South Africa, with one third reporting a pregnancy by the age of 20 years. Adolescents are also at disproportionately high risk of HIV infection. A high proportion of lifetime HIV risk is accrued before age 25 years. This study from KwaZulu-Natal, comparing health service utilization and mother-to-child transmission rates between adult and adolescent mothers, report some concerning disparities.  The majority of mothers had attended frequently for antenatal care and been tested for HIV.  Adolescent mothers were more likely to have tested late (in the last trimester of pregnancy or postnatally), less likely to have had a CD4 count or to have received an effective prevention of mother-to-child transmission regimen.  In addition, adolescent mothers were more likely to be living in adverse social conditions than their adult counterparts.  These disparities resulted in higher HIV mother-to-child transmission rates among adolescents than in adults.

The findings highlight the differential service delivery, access to care and service uptake in the adolescent age-group.  Given the high rates of pregnancy and HIV in this age-group, there is a need to focus on adolescents if elimination of new HIV infections among children is to be achieved. Strategies to make reproductive health services more accessible to adolescents are urgently required. This must include addressing the particular vulnerabilities of adolescents as well as training of healthcare providers.     

Africa
South Africa
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High uptake of home-based testing of regular male partners of women attending for ANC services

Home visits during pregnancy enhance male partner HIV counselling and testing in Kenya: a randomized clinical trial.

Onyango OA, Grace JS, James K, Barbra R, John K, Daisy K, Carey F. AIDS. 2013 Aug 12. [Epub ahead of print]

Background:  HIV testing male partners of pregnant women may decrease HIV transmission to women and promote uptake of prevention of mother-to-child HIV transmission (PMTCT) interventions. However, it has been difficult to access male partners in antenatal care (ANC) clinics. We hypothesized that home visits to offer HIV testing to partners of women attending ANC would increase partner HIV testing.

Methods:  Women attending their first ANC were enrolled, interviewed using smartphone audio-computer assisted self-interviews and randomized to home visits or written invitations for male partners to come to clinic, if they were married or cohabiting, unaccompanied by partners and had no prior couple HIV counselling and testing (CHCT). Enrolled men were offered CHCT (HIV testing and mutual disclosure). Prevalence of CHCT, male HIV seropositivity, couple serodiscordance and intimate partner violence, reported as physical threat from partner, were compared at 6 weeks.

Results:  Among 495 women screened, 312 were eligible, and 300 randomized to clinic-based or home-based CHCT. Median age was 22 years (interquartile range 20-26 years), and 87% were monogamous. CHCT was significantly higher in home-visit than in clinic-invitation arm (n = 128, 85% vs. n = 54, 36%; P < 0.001). Home-arm identified more HIV-seropositive men (12.0 vs. 8.0%; P = 0.248) and more HIV-discordant couples (14.7 vs. 4.7%; P = 0.003). There was no difference in intimate partner violence.

Conclusion:  Home visits of pregnant women were safe and resulted in more male partner testing and mutual disclosure of HIV status. This strategy could facilitate prevention of maternal HIV acquisition, improve PMTCT uptake and increase male HIV diagnosis.

Abstract access

Editor’s notes: The evidence to support home-based testing as a means to increase knowledge of HIV status is becoming well-established. This trial which looked at focused home-based HIV testing for partners of pregnant women examined the specific question of how to better engage men in antenatal testing. This focused home-based approach more than doubled the number of male partners who tested, when compared with facility-based testing. The authors highlight that the 85% uptake is higher than other general door-to-door home-based or community-based approaches. The study also explored intimate partner violence as a potential adverse consequence of the intervention and found no difference between study arms. While the sample in this study is relatively modest, the findings may provide a key to unlock several challenges at once. It could increase the relatively low uptake of testing in sexually active men, use antenatal care (ANC) as an opportunity to prevent onward transmission between partners in sero-discordant relationships and help address non-disclosure as a barrier to effective prevention of HIV transmission from mother to child.

Africa
Kenya
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Poor treatment outcomes for children taking abacavir in South Africa

Poor Early Virologic Performance and Durability of Abacavir-based First-line Regimens for HIV-infected Children.

Technau KG, Lazarus E, Kuhn L, Abrams EJ, Sorour G, Strehlau R, Reubenson G, Davies MA, Coovadia A. Pediatr Infect Dis  J. 2013 Aug;32(8):851-855.

Background:  Concerns about stavudine (d4T) toxicity have led to increased use of abacavir (ABC) in first-line pediatric antiretroviral treatment (ART) regimens. Field experience with ABC in ART-naïve children is limited.

Methods:  Deidentified demographic, clinical and laboratory data on HIV-infected children initiating ART between 2004 and 2011 in a large pediatric HIV treatment program in Johannesburg, South Africa, were used to compare viral suppression at 6 and 12 months by initial treatment regimen, time to suppression (<400 copies/mL) and rebound (>1000 copies/mL after initial suppression). Adjusted logistic regression was used to investigate confounders and calendar effects.

Results:  Two thousand thirty-six children initiated either d4T/3TC- or ABC/3TC-based first-line regimens in combination with either boosted lopinavir (LPV/r) or efavirenz (EFV). 1 634 received d4T regimens (LPV/r n = 672; EFV n = 962) and 402 ABC regimens (LPV/r n = 192; EFV n = 210). At 6 and 12 months on ART, viral suppression rate was poorer in ABC versus d4T groups within both the LPV/r and EFV groups (P < 0.0001 for all points). In ABC groups, time to suppression was significantly slower (log-rank P < 0.0001 and P = 0.0092 for LPV/r- and EFV-based, respectively) and time to rebound after suppression significantly faster (log-rank P = 0.014 and P = 0.0001 for LPV/r- and EFV-based, respectively). Logistic regression confirmed the worse outcomes in the ABC groups even after adjustment for confounders.

Conclusion:  Data from this urban pediatric ART service program show significantly poorer virological performance of ABC compared with d4T-based regimens, a signal that urgently warrants further investigation.

Abstract access

Editor’s notes: Given the toxicity of stavudine (d4T), there has been a move towards using abacavir (ABC) with lamivudine (3TC) as the nucleoside backbone in children, despite few data on effectiveness of this regimen for treatment in paediatric HIV.  In adults, ABC has been shown to be less potent than other NRTIs. This retrospective cohort study from a single large paediatric HIV treatment programme in South Africa shows significantly poorer virological outcomes for ABC compared to d4T.  These findings persisted despite higher CD4 percentages in the ABC group, and were consistent for both boosted lopinavir and efavirenz regimens.  The reasons for these findings are not clear and may be due to ABC and 3TC sharing the same cross-resistant mutation (M184V) unlike d4T, and to ABC having a lower genetic barrier to resistance than d4T.  

The study has the inherent limitations of a retrospective cohort; in particular the types of formulations and doses, and data on ART exposure during pregnancy and breastfeeding, were not available for analysis.  Notwithstanding these limitations, the study raises an important concern about the possible lower effectiveness of ABC compared to other nucleoside analogues, a finding that has also been observed in adults.  Notably, the recent PENTA-5 trial showed more rapid evolution of resistance with a failing ABC-based regimen. 

If confirmed, these findings have significant public health implications as they may influence longer term outcomes with reduced regimen options at later time points. Given that ABC is recommended as the first line regimen in children and that children have fewer drug options than adults, further investigation of the effectiveness of ABC in children is urgently needed. 

Africa
South Africa
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Improved PMTCT strategies substantially reduce transmission rates in South Africa

Reduction in perinatal HIV infections in KwaZulu-Natal, South Africa, in the era of more effective prevention of mother to child transmission interventions (2004-2012)

Moodley P, Parboosing R, Moodley D., Acquir Immune Defic Syndr. 2013 Jul 1;63(3):410-5. doi: 10.1097/QAI.0b013e3182926931.

Objective: To describe a trend in perinatal HIV transmission associated with the implementation of rapidly changing prevention of mother to child transmission (PMTCT) interventions from 2004 to 2012.

Method: Retrospective analysis of infant HIV polymerase chain reaction results of infants from 2004 to 2012 archived from a Laboratory Information System.

Setting: KwaZulu-Natal, South Africa.

Main outcome measure: HIV infection in infants aged 4-8 weeks.

Results:  The proportion of 4- to 8-week-old infants who tested HIV polymerase chain reaction positive decreased significantly (P < 0.0001) from 27.5% in 2004 to 2.9% in 2012. The reduction rates in perinatal HIV infections in 4- to 8-week-old HIV-exposed infants decreased significantly (P < 0.0001) by 48.7% following single-dose nevirapine (sdNVP) (2005 to April 2008), 68.4% with zidovudine from 28 weeks and sdNVP together with triple antiretroviral therapy for women with CD4 cell count < 200 cells/mm (May 2008-April 2010), and 89.5% with zidovudine from 14 weeks, sdNVP, and triple antiretroviral therapy for women with CD4 cell count < 350 cells/mm (May 2010-December 2012).

Conclusions: We show an almost 10-fold reduction in mother to child transmission from 2004 to 2012 in infants aged 4-8 weeks during a rapid implementation of more complex and robust PMTCT interventions. The significant reductions in mother to child transmission in the South African PMTCT program are encouraging for a middle-income country with the second highest antenatal HIV prevalence in the world.

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Editor’s notes: This retrospective study analyzed data from routine infant HIV tests, and thus provides empirical evidence of the effect of implementation of rapidly changing PMTCT guidelines in this high HIV prevalence setting over the past decade.  During this period, HIV prevalence among women attending antenatal clinics did not change substantially (between 37-39%), but the prevalence among HIV exposed infants aged 4-8 weeks decreased dramatically from 27.6% (95%CI 19.1-36.2) in 2004 to 2.9% (95%CI 2.8-3.0%) in 2012.  A similar decrease was seen among infants aged eight weeks to 15 months (30.1% in 2004 to 7.3% in 2012). The higher rate in the older infants is likely due to transmission through breastfeeding. The data from 2010-2012 are based on implementation of WHO Option A, and this changed in April 2013 to Option B (triple ARVs starting at 14 weeks gestation and continued intrapartum and through delivery if not breastfeeding, or until one week after cessation of all breastfeeding, with the infant given daily NVP or AZT from birth through age 4-6 weeks regardless of infant feeding method).  The expectation is that Option B, and B Plus (lifelong ART for all HIV-infected pregnant women regardless of CD4 count) should reduce MTCT to below 5% by 2015.  

Africa
South Africa
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