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1.
Int J Health Policy Manag ; 11(5): 610-628, 2022 May 01.
Article in English | MEDLINE | ID: mdl-33131222

ABSTRACT

BACKGROUND: We evaluated continuous quality improvement (CQI) targeting antenatal HIV care quality in rural South Africa using a stepped-wedge cluster-randomised controlled trial (Management and Optimisation of Nutrition, Antenatal, Reproductive, Child health, MONARCH) and an embedded process evaluation. Here, we present results of the process evaluation examining determinants of CQI practice and 'normalisation.' METHODS: A team of CQI mentors supported public-sector health workers in seven primary care clinics to (1) identify root causes of poor HIV viral load (VL) monitoring among pregnant women living with HIV and repeat HIV testing among pregnant women not living with HIV, and (2) design and iteratively test their own solutions. We used a mixed methods evaluation with field notes from CQI mentors ('dose' and 'reach' of CQI, causes of poor HIV care testing rates, implemented change ideas); patient medical records (HIV care testing by clinic and time step); and semi-structured interviews with available health workers. We analysed field notes andsemi-structured interviews for determinants of CQI implementation and 'normalisation' using Normalisation Process Theory (NPT) and Tailored Implementation of Chronic Diseases (TICD) frameworks. RESULTS: All interviewed health workers found the CQI mentors and methodology helpful for quality improvement. Total administered 'dose' was higher than planned but 'reach' was limited by resource constraints, particularly staffing shortages. Simple workable improvements to identified root causes were implemented, such as a patient tracking notebook and results filing system. VL monitoring improved over time, but not repeat HIV testing. Besides resource constraints, gaps in knowledge of guidelines, lack of leadership, poor clinical documentation, and data quality gaps reduced CQI implementation fidelity and normalisation. CONCLUSION: While CQI holds promise, we identified several health system challenges. Priorities for policy makers include improving staffing and strategies to improve clinical documentation. Additional support with implementing clinical guidelines and improving routine data quality are needed. Normalising CQI may be challenging without concurrent health system improvements.


Subject(s)
HIV Infections , Quality Improvement , Child , Female , HIV Infections/diagnosis , HIV Testing , Humans , Pregnancy , Rural Population , South Africa
2.
PLoS Med ; 17(10): e1003150, 2020 10.
Article in English | MEDLINE | ID: mdl-33027246

ABSTRACT

BACKGROUND: Evidence for the effectiveness of continuous quality improvement (CQI) in resource-poor settings is very limited. We aimed to establish the effects of CQI on quality of antenatal HIV care in primary care clinics in rural South Africa. METHODS AND FINDINGS: We conducted a stepped-wedge cluster-randomised controlled trial (RCT) comparing CQI to usual standard of antenatal care (ANC) in 7 nurse-led, public-sector primary care clinics-combined into 6 clusters-over 8 steps and 19 months. Clusters randomly switched from comparator to intervention on pre-specified dates until all had rolled over to the CQI intervention. Investigators and clusters were blinded to randomisation until 2 weeks prior to each step. The intervention was delivered by trained CQI mentors and included standard CQI tools (process maps, fishbone diagrams, run charts, Plan-Do-Study-Act [PDSA] cycles, and action learning sessions). CQI mentors worked with health workers, including nurses and HIV lay counsellors. The mentors used the standard CQI tools flexibly, tailored to local clinic needs. Health workers were the direct recipients of the intervention, whereas the ultimate beneficiaries were pregnant women attending ANC. Our 2 registered primary endpoints were viral load (VL) monitoring (which is critical for elimination of mother-to-child transmission of HIV [eMTCT] and the health of pregnant women living with HIV) and repeat HIV testing (which is necessary to identify and treat women who seroconvert during pregnancy). All pregnant women who attended their first antenatal visit at one of the 7 study clinics and were ≥18 years old at delivery were eligible for endpoint assessment. We performed intention-to-treat (ITT) analyses using modified Poisson generalised linear mixed effects models. We estimated effect sizes with time-step fixed effects and clinic random effects (Model 1). In separate models, we added a nested random clinic-time step interaction term (Model 2) or individual random effects (Model 3). Between 15 July 2015 and 30 January 2017, 2,160 participants with 13,212 ANC visits (intervention n = 6,877, control n = 6,335) were eligible for ITT analysis. No adverse events were reported. Median age at first booking was 25 years (interquartile range [IQR] 21 to 30), and median parity was 1 (IQR 0 to 2). HIV prevalence was 47% (95% CI 42% to 53%). In Model 1, CQI significantly increased VL monitoring (relative risk [RR] 1.38, 95% CI 1.21 to 1.57, p < 0.001) but did not improve repeat HIV testing (RR 1.00, 95% CI 0.88 to 1.13, p = 0.958). These results remained essentially the same in both Model 2 and Model 3. Limitations of our study include that we did not establish impact beyond the duration of the relatively short study period of 19 months, and that transition steps may have been too short to achieve the full potential impact of the CQI intervention. CONCLUSIONS: We found that CQI can be effective at increasing quality of primary care in rural Africa. Policy makers should consider CQI as a routine intervention to boost quality of primary care in rural African communities. Implementation research should accompany future CQI use to elucidate mechanisms of action and to identify factors supporting long-term success. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov under registration number NCT02626351.


Subject(s)
HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Prenatal Care/standards , Viral Load/statistics & numerical data , Adult , Anti-HIV Agents/therapeutic use , Female , HIV Infections/blood , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Seropositivity/diagnosis , Humans , Implementation Science , Practice Patterns, Nurses' , Pregnancy , Primary Health Care , Process Assessment, Health Care , Quality Improvement , Quality Indicators, Health Care , RNA, Viral/blood , Rural Population , South Africa , Total Quality Management , Young Adult
3.
South Afr J HIV Med ; 20(1): 847, 2019.
Article in English | MEDLINE | ID: mdl-31061722

ABSTRACT

BACKGROUND: Preconception antiretroviral therapy (PCART) followed by sustained viral suppression is effective in preventing mother-to-child transmission of HIV. The rates of persistent and transient viraemia in such patients have not been prospectively assessed in South Africa. OBJECTIVES: We determined the prevalence of transient and persistent viraemia in HIV-positive women entering antenatal care on PCART and studied variables associated with viraemia. METHODS: We performed a prospective cross-sectional observational study of HIV-positive pregnant women presenting to a primary healthcare facility in KwaZulu-Natal. All had received at least 6 months of first-line PCART. Viral load (VL) was measured, patients were interviewed, adherence estimated using a visual analogue scale and adherence counselling provided. Viral load was repeated after 4 weeks where baseline VL exceeded 50 copies/mL. RESULTS: We enrolled 82 participants. Of them, 59 (72%) pregnancies were unplanned. Fifteen participants (18.3%) were viraemic at presentation with VL > 50 copies/mL. Of these, seven (8.5%) had viral suppression (VL < 50 copies/mL), and eight remained viraemic at the second visit. Adherence correlated significantly with viraemia at baseline. Level of knowledge correlated with adherence but not with lack of viral suppression at baseline. Socio-economic indicators did not correlate with viraemia. No instances of vertical transmission were observed at birth. CONCLUSIONS: Approximately 20% of women receiving PCART may demonstrate viraemia. Half of these may be transient. Poor adherence is associated with viraemia, and efforts to encourage and monitor adherence are essential. The rate of unplanned pregnancies is high, and antiretroviral therapy programmes should focus on family planning needs of women in the reproductive age group to prevent viral non-suppression prior to pregnancy. KEYWORDS: Preconception Antiretroviral Therapy; HIV; Viraemia; Antenatal Care; Adherence.

4.
Int J Gynaecol Obstet ; 133(2): 152-5, 2016 May.
Article in English | MEDLINE | ID: mdl-26948340

ABSTRACT

OBJECTIVE: To determine the prevalence of repeat teenage pregnancy and the interval between first/most recent and repeat pregnancies, as well as to evaluate the sexual/reproductive health characteristics of teenagers with repeat pregnancies. METHODS: A prospective observational study was undertaken at a hospital in KwaZulu-Natal, South Africa, between May and September 2013. Teenagers aged 13-19years who were pregnant, had recently delivered, or had terminated a pregnancy were enrolled. A questionnaire was used to obtain data. RESULTS: Among 341 participants, 281 (82.4%) were seen for a first pregnancy and 60 (17.6%) for a repeat pregnancy. The interval between first/most recent and repeat pregnancies was 24months or lower in 45 (75.0%) of repeat pregnancy participants. Only 58 (17.0%) participants had previously used contraception (54 [93.1%] of whom stopped within 12months) and 28 (8.2%) had used emergency contraception. More participants with repeat pregnancy than with first pregnancy had a positive HIV status (18 [30.0%] vs 26 [9.3%]; P<0.001), more than one sexual partner in the past 12months (21 [35.0%] vs 35 [12.5%]; P<0.001), and a partner at least 5years older (38 [63.3%] vs 128 [45.6%]; P<0.001). CONCLUSION: High repeat pregnancy rates, low contraception use, and high HIV prevalence among teenagers in South Africa is worrying. Focused interventions targeting teenagers following their first pregnancy need to be urgently implemented.


Subject(s)
Birth Intervals/statistics & numerical data , Contraception Behavior/statistics & numerical data , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Pregnancy in Adolescence/statistics & numerical data , Adolescent , Female , Humans , Pregnancy , Prospective Studies , South Africa/epidemiology , Surveys and Questionnaires , Young Adult
5.
BMJ Qual Saf ; 22(11): 891-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23204513

ABSTRACT

OBJECTIVE: New approaches are needed to evaluate quality improvement (QI) within large-scale public health efforts. This case report details challenges to large-scale QI evaluation, and proposes solutions relying on adaptive study design. STUDY DESIGN: We used two sequential evaluative methods to study a QI effort to improve delivery of HIV preventive care in public health facilities in three districts in KwaZulu-Natal, South Africa, over a 3-year period. We initially used a cluster randomised controlled trial (RCT) design. PRINCIPAL FINDINGS: During the RCT study period, tensions arose between intervention implementation and evaluation design due to loss of integrity of the randomisation unit over time, pressure to implement changes across the randomisation unit boundaries, and use of administrative rather than functional structures for the randomisation. In response to this loss of design integrity, we switched to a more flexible intervention design and a mixed-methods quasiexperimental evaluation relying on both a qualitative analysis and an interrupted time series quantitative analysis. CONCLUSIONS: Cluster RCT designs may not be optimal for evaluating complex interventions to improve implementation in uncontrolled 'real world' settings. More flexible, context-sensitive evaluation designs offer a better balance of the need to adjust the intervention during the evaluation to meet implementation challenges while providing the data required to evaluate effectiveness. Our case study involved HIV care in a resource-limited setting, but these issues likely apply to complex improvement interventions in other settings.


Subject(s)
HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Public Health , Quality Improvement , Female , HIV Infections/transmission , Humans , Infant, Newborn , Motivation , Pregnancy , Program Evaluation , Research Design , South Africa
6.
J Acquir Immune Defic Syndr ; 56(2): e45-8, 2011 Feb 01.
Article in English | MEDLINE | ID: mdl-21084998

ABSTRACT

OBJECTIVE: To model the effect of health systems performance on rates of mother-to-child HIV transmission. METHODS: We modeled the effect of variation in performance of the multiple steps of different prevention of mother-to-child transmission (PMTCT) protocols using hypothetical and reported data. SETTING: Data from a PMTCT program in a large province in South Africa was used to compare model predictions with reported outcomes for mother-to-child HIV transmission. MAIN OUTCOME MEASURE: Perinatal HIV transmission was predicted for infants of 6 weeks of age. RESULTS: HIV-infected pregnant women who fulfill eligibility criteria are initiated on lifelong antiretroviral treatment, whereas noneligible HIV-infected women and their infants receive single-dose nevirapine in a health system functioning at reported performance levels, and the overall vertical transmission rate would be 19.5%. Adding azidothymidine for women not eligible for lifelong treatment would further decrease the overall transmission rates only marginally to 17%. If the same steps were accomplished at 95% reliability, then the overall transmission rates would be 9.4% and 4.1%, respectively. CONCLUSIONS: Introduction of more effective combination antiretroviral interventions will yield only marginal reductions in childhood HIV infections and mortality unless health systems achieve high levels of performance at each step of the PMTCT pathway. Investment in and support for the mechanisms of delivering and sustaining PMTCT interventions at scale are required if gains in maternal and child survival are to be realized in countries highly affected by HIV.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , Delivery of Health Care/methods , HIV Infections/epidemiology , HIV Infections/transmission , Infectious Disease Transmission, Vertical/prevention & control , Quality of Health Care , Female , HIV Infections/prevention & control , Humans , Incidence , Infant , Infant, Newborn , Pregnancy , South Africa/epidemiology , Treatment Outcome
7.
Clin Infect Dis ; 49(1): 93-101, 2009 Jul 01.
Article in English | MEDLINE | ID: mdl-19489712

ABSTRACT

BACKGROUND: Septic shock is common and results in significant morbidity and mortality. Adjunctive treatment with corticosteroids is common, but definitive data are lacking. We aimed to determine the efficacy and safety of corticosteroid therapy among patients with septic shock. METHODS: Medline, Embase, Cochrane Library, Web of Science, and Google Scholar were searched for randomized trials and observational studies published from January 1993 through December 2008. Studies were selected if they included adults with septic shock, discussed treatment with intravenous corticosteroids, and reported at least 1 outcome of interest (e.g., mortality, shock reversal, or incidence of superinfection). Two reviewers independently agreed on eligibility, assessed methodologic quality, and abstracted data. RESULTS: Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated for 28-day all-cause mortality, shock reversal at 7 days, and incidence of superinfection with use of random-effects models. Analyses, stratified by adrenal responsiveness, were prespecified. Eight studies (6 randomized trials) involving a total of 1876 patients were selected. Overall, corticosteroid therapy did not result in a statistically significant difference in mortality (42.2% [369 of 875 patients] vs. 38.4% [384 of 1001]; RR, 1.00; 95% CI, 0.84-1.18). A statistically significant difference in the incidence of shock reversal at 7 days was observed between patients who received corticosteroids and those who did not (64.9% [314 of 484 patients] vs. 47.5% [228 of 480]; RR, 1.41; 95% CI, 1.22-1.64), with similar point estimates for both corticotropin stimulation test responders and nonresponders. No statistically significant difference was found in the incidence of superinfection between patients treated with corticosteroids and patients not treated with corticosteroids (25.3% [114 of 450 patients] vs. 22.7% [100 of 441]; RR, 1.11; 95% CI, 0.86-1.42). CONCLUSIONS: In patients with septic shock, corticosteroid therapy appears to be safe but does not reduce 28-day all-cause mortality rates. It does, however, significantly reduce the incidence of vasopressor-dependent shock, which may be a clinically worthwhile goal.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Shock, Septic/drug therapy , Humans , Shock, Septic/mortality , Treatment Outcome
8.
PLoS One ; 4(5): e5483, 2009.
Article in English | MEDLINE | ID: mdl-19434234

ABSTRACT

BACKGROUND: Recent changes to South Africa's prevention of mother-to-child transmission of HIV (PMTCT) guidelines have raised hope that the national goal of reducing perinatal HIV transmission rates to less than 5% can be attained. While programmatic efforts to reach this target are underway, obtaining complete and accurate data from clinical sites to track progress presents a major challenge. We assessed the completeness and accuracy of routine PMTCT data submitted to the district health information system (DHIS) in three districts of Kwazulu-Natal province, South Africa. METHODOLOGY/PRINCIPAL FINDINGS: We surveyed the completeness and accuracy of data reported for six key PMTCT data elements between January and December 2007 from all 316 clinics and hospitals in three districts. Through visits to randomly selected sites, we reconstructed reports for the same six PMTCT data elements from clinic registers and assessed accuracy of the monthly reports previously submitted to the DHIS. Data elements were reported only 50.3% of the time and were "accurate" (i.e. within 10% of reconstructed values) 12.8% of the time. The data element "Antenatal Clients Tested for HIV" was the most accurate data element (i.e. consistent with the reconstructed value) 19.8% of the time, while "HIV PCR testing of baby born to HIV positive mother" was the least accurate with only 5.3% of clinics meeting the definition of accuracy. CONCLUSIONS/SIGNIFICANCE: Data collected and reported in the public health system across three large, high HIV-prevalence Districts was neither complete nor accurate enough to track process performance or outcomes for PMTCT care. Systematic data evaluation can determine the magnitude of the data reporting failure and guide site-specific improvements in data management. Solutions are currently being developed and tested to improve data quality.


Subject(s)
Database Management Systems , Delivery of Health Care/statistics & numerical data , Government Programs/statistics & numerical data , HIV Infections/prevention & control , HIV Infections/transmission , Infectious Disease Transmission, Vertical/prevention & control , Infectious Disease Transmission, Vertical/statistics & numerical data , Female , HIV Infections/epidemiology , Humans , Pregnancy , Registries , South Africa/epidemiology
9.
AIDS ; 22(11): 1333-43, 2008 Jul 11.
Article in English | MEDLINE | ID: mdl-18580613

ABSTRACT

OBJECTIVES: Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting. METHODS: HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring. RESULTS: All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression. CONCLUSION: Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , HIV-1 , Adolescent , Adult , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , Drug Administration Schedule , Drug Resistance, Viral/genetics , Feasibility Studies , Female , HIV Infections/immunology , HIV Infections/transmission , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Mutation , Nevirapine/therapeutic use , Patient Compliance , Pilot Projects , Pregnancy , Pregnancy Complications, Infectious , Socioeconomic Factors , Treatment Outcome , Viral Load
10.
AIDS Res Hum Retroviruses ; 24(2): 265-70, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18284325

ABSTRACT

Multiple HIV-1-specific cytokine and proliferative responses by CD4(+) T cells have not been studied in acutely infected infants. Using an intracellular cytokine staining assay, 34 untreated clade C HIV-1-infected infants (2-102 days old) were assessed for IFN-gamma, 28/34 for IL-2, and 26/34 for TNF-alpha responses to all HIV-1 proteins. Responses were detected in 29%, 36%, and 15% of infants, respectively. Twelve of the original 34 infants were then studied longitudinally for 14 months to determine the effect of viral load on IFN-gamma Gag-specific responses: seven infants were treated for 1 year, stopped treatment, and resumed when CD4% was < 20 and five infants were treated only when the CD4% was <20. Following treatment cessation, there was an immediate increase in viral load followed by an increase in the magnitude of CD4(+) Gag-specific responses. Despite this, the majority of infants (54%) had to restart treatment by 24 months of age, indicating that the immune responses were antigen driven but not associated with protection. Among untreated infants HIV-specific CD4(+) responses were detected sporadically indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , gag Gene Products, Human Immunodeficiency Virus/immunology , Animals , CD4 Lymphocyte Count , Cell Proliferation , Cells, Cultured , Humans , Infant , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Longitudinal Studies , Tumor Necrosis Factor-alpha/biosynthesis , Viral Load
11.
Curr Opin HIV AIDS ; 3(2): 180-5, 2008 Mar.
Article in English | MEDLINE | ID: mdl-19372963

ABSTRACT

PURPOSE OF REVIEW: At a time when highly effective drugs to prevent peripartum transmission of HIV are readily available and affordable, HIV remains the single most important cause of the death of infants and young children in southern and east Africa. RECENT FINDINGS: Evidence from the past 5 years highlights four main points. The survival of children born to HIV-infected mothers relies on the mothers remaining well and alive. Suboptimal feeding practices of HIV-exposed infants can significantly increase infant mortality aside of any impact on postnatal transmission of HIV. Antiretroviral drugs are now available that can reduce morbidity and mortality in infected women as well as the transmission of HIV to their infants. Finally, the inability of health systems to deliver prevention of mother-to-child transmission services is the greatest obstacle to reducing HIV infection among infants and improving maternal and child survival. SUMMARY: The goal of improved maternal and child survival and not just the avoidance of HIV infection in infants must be the goal of prevention of mother-to-child transmission programmes. Research is needed to identify interventions that will improve the ability of health systems to deliver prevention of mother-to-child transmission services in addition to new and more effective therapeutic interventions.

12.
J Virol ; 81(23): 12775-84, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17881456

ABSTRACT

Human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa typically progress to AIDS or death by 2 years of life in the absence of antiretroviral therapy. This rapid progression to HIV disease has been related to immaturity of the adaptive immune response in infants. We screened 740 infants born to HIV-infected mothers and tracked development and specificity of HIV-specific CD8+ T-cell responses in 63 HIV-infected infants identified using gamma interferon enzyme-linked immunospot assays and intracellular cytokine staining. Forty-four in utero-infected and 19 intrapartum-infected infants were compared to 45 chronically infected children >2 years of age. Seventy percent (14 of 20) in utero-infected infants tested within the first week of life demonstrated HIV-specific CD8+ T-cell responses. Gag, Pol, and Nef were the principally targeted regions in chronic pediatric infection. However, Env dominated the overall response in one-third (12/36) of the acutely infected infants, compared to only 2/45 (4%) of chronically infected children (P = 0.00083). Gag-specific CD4+ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virus-specific CD8+ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , HIV Infections/congenital , HIV Infections/immunology , T-Lymphocyte Subsets/immunology , Africa South of the Sahara , CD4-Positive T-Lymphocytes/immunology , Female , HIV/immunology , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Interferons/biosynthesis , Male , Pregnancy , Pregnancy Complications, Infectious , gag Gene Products, Human Immunodeficiency Virus/immunology , nef Gene Products, Human Immunodeficiency Virus/immunology , pol Gene Products, Human Immunodeficiency Virus/immunology
13.
AIDS ; 21(10): 1253-61, 2007 Jun 19.
Article in English | MEDLINE | ID: mdl-17545701

ABSTRACT

OBJECTIVES: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/immunology , Nevirapine/administration & dosage , CD4 Lymphocyte Count , Disease Progression , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/immunology , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Morbidity , Mothers , Perinatal Care/methods , South Africa/epidemiology , Viral Load , Viremia/immunology
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