OpenUCT :: Browsing by Subject "Viral load"

Browsing by Subject "Viral load"

Now showing 1 - 20 of 32

Open Access
Anaemia in acute HIV-1 subtype C infection
(Public Library of Science, 2008) Mlisana, Koleka; Auld, Sara C; Grobler, Anneke; Loggerenberg, Francois van; Williamson, Carolyn; Iriogbe, Itua; Sobieszczyk, Magdalena E; Karim, Salim S Abdool; Team, for the CAPRISA Acute Infection Study
BACKGROUND: The high prevalence of anaemia and the increased morbidity and mortality associated with anaemia during AIDS has been well described yet there has been little information about anaemia and changes in haemoglobin levels during acute and early HIV-1 infection. METHODS: HIV-negative women (n = 245) were enrolled into an observational cohort as part of the Centre for the AIDS Programme of Research in South Africa (CAPRISA) Acute Infection Study. Acute infection was diagnosed following a positive HIV RNA PCR in the absence of antibodies, or detection of HIV-1 antibodies within 3 months of a previously negative antibody test. Haemotologic parameters were assessed before infection and at regular intervals in the first twelve months of HIV infection. RESULTS: Fifty-seven participants with acute HIV infection were identified at a median of 14.5 days post-infection (range 10-81) and were enrolled in the CAPRISA Acute Infection cohort at a median of 41 days post-infection (range 15-104). Mean haemoglobin prior to HIV-1 infection was 12.7 g/dL, with a mean decline of 0.46 g/dL following infection. The prevalence of anaemia increased from 25.0% prior to HIV-1 infection to 52.6% at 3 months post-infection, 61.1% at 6 months post-infection, and 51.4% at 12 months post-infection. CONCLUSIONS: Haematologic derangements and anaemia with a trend towards iron deficiency are common with acute HIV-1 subtype C infection in this small cohort. The negative impact of anaemia concurrent with established HIV infection upon morbidity and mortality has been well documented but the prognostic potential and long-term effects of anaemia during acute HIV-1 infection remain unknown.
Open Access
Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa
(Public Library of Science, 2014) Fatti, Geoffrey; Mothibi, Eula; Meintjes, Graeme; Grimwood, Ashraf
Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25-54 years) in routine care settings in South Africa. METHODS: A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. RESULTS: 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29-1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26-1.64), particularly for the period 7-60 months of treatment, asHR = 1.73 (95% CI: 1.44-2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78-0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23-1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56-0.85) and 0.64 (95% CI: 0.47-0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3-33.2) lower in older adults. CONCLUSIONS: Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies.
Open Access
Better antiretroviral therapy outcomes at primary healthcare facilities: an evaluation of three tiers of ART services in four South African provinces
(Public Library of Science, 2010) Fatti, Geoffrey; Grimwood, Ashraf; Bock, Peter
BACKGROUND: There are conflicting reports of antiretroviral therapy (ART) effectiveness comparisons between primary healthcare (PHC) facilities and hospitals in low-income settings. This comparison has not been evaluated on a broad scale in South Africa. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa, enrolled between 2004 and 2007. Kaplan-Meier estimates, competing-risks Cox regression, generalised estimating equation population-averaged models and logistic regression were used to compare death, loss to follow-up (LTFU) and virological suppression (VS) between PHC, district and regional hospitals. 29 203 adults from 47 PHC facilities, nine district hospitals and three regional hospitals were included. Patients at PHC facilities had more advanced WHO stage disease when starting ART. Retention in care was 80.1% (95% CI: 79.3%-80.8%), 71.5% (95% CI: 69.1%-73.8%) and 68.7% (95% CI: 67.0%-69.7%) at PHC, district and regional hospitals respectively, after 24 months of treatment ( P <0.0001). In adjusted regression analyses, LTFU was independently increased at regional hospitals (aHR 2.19; 95% CI: 1.94−2.47) and mortality was independently elevated at district hospitals (aHR 1.60; 95% CI: 1.30−1.99) compared to PHC facilities after 12 months of ART. District and regional hospital patients had independently reduced probabilities of VS, aOR 0.76 (95% CI: 0.59−0.97) and 0.64 (95% CI: 0.56−0.75) respectively compared to PHC facilities over 24 months of treatment. Conclusions/Significance: ART outcomes were superior at PHC facilities, despite PHC patients having more advanced clinical stage disease when starting ART, suggesting that ART can be adequately provided at this level and supporting the South African government's call for rapid up-scaling of ART at the primary level of care. Further prospective research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or patient co-morbidity at hospital level.
Open Access
Broadly neutralizing antibody responses in a large longitudinal sub-Saharan HIV primary infection cohort
(Public Library of Science, 2016) Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin; Murrell, Ben; Price, Matt A; Wickramasinghe, Lalinda; Ramos, Alejandra; Bian, Charoan B; Simek, Melissa; Allen, Susan; Karita, Etienne; Kilembe, William; Lakhi, Shabir; Inambao, Mubiana; Kamali, Anatoli; Sanders, Eduard J; Anzala, Omu; Edward, Vinodh; Bekker, Linda-Gail; Tang, Jianming; Gilmour, Jill; Kosakovsky-Pond, Sergei L; Phung, Pham; Wrin, Terri; Crotty, Shane; Godzik, Adam; Poignard, Pascal
Author Summary Understanding how HIV-1-broadly neutralizing antibodies (bnAbs) develop during natural infection is essential to the design of an efficient HIV vaccine. We studied kinetics and correlates of neutralization breadth in a large sub-Saharan African longitudinal cohort of 439 participants with primary HIV-1 infection. Broadly nAb responses developed in 15% of individuals, on average three years after infection. Broad neutralization was associated with high viral load, low CD4+ T cell counts, virus subtype C infection and HLA*A3(-) genotype. A correlation with high overall plasma IgG levels and anti-Env binding titers was also found. Specificity mapping of the bnAb responses showed that glycan-dependent epitopes, in particular the N332 region, were most commonly targeted, in contrast to other bnAb epitopes, suggesting that the HIV Env N332-glycan epitope region may be a favorable target for vaccine design.
Open Access
CD8+ T-cell interleukin-7 receptor alpha expression as a potential indicator of disease status in HIV-infected children
(Public Library of Science, 2008) Sharma, Tanvi S; Hughes, Jane; Murillo, Amarylis; Riley, Joanne; Soares, Andreia; Little, Francesca; Mitchell, Charles D; Hanekom, Willem A
BACKGROUND: Initiation and modification of antiretroviral therapy in HIV-infected children depend on viral load and CD4+ T-cell count. However, these surrogates have limitations, and complementary immunological markers to assess therapeutic response are needed. Our aim was to evaluate CD8+ T-cell expression of CD127 as a marker of disease status in HIV-infected children, based on adult data suggesting its usefulness. We hypothesized that CD127 expression on CD8+ T-cells is lower in children with more advanced disease. METHODS: In a cross-sectional evaluation, we used flow cytometry to measure CD127+ expression on CD8+ T-cells in whole blood from HIV-infected children with varying disease status. This was compared with expression of CD38 on this subset, currently used in clinical practice as a marker of disease status. RESULTS: 51 HIV-infected children were enrolled. There was a strong positive correlation between CD127 expression on CD8+ T-cells and CD4+ T-cell count, and height and weight z-scores, and a strong negative correlation between CD127 expression and viral load. In contrast, we found no association between CD38 expression and these disease status markers. CONCLUSIONS: CD8+ T-cell CD127 expression is significantly higher in children with better HIV disease control, and may have a role as an immunologic indicator of disease status. Longitudinal studies are needed to determine the utility of this marker as a potential indicator of HIV disease progression.
Open Access
Collaborative care for the detection and management of depression among adults receiving antiretroviral therapy in South Africa: study protocol for the CobALT randomised controlled trial
(BioMed Central, 2018-03-22) Fairall, Lara; Petersen, Inge; Zani, Babalwa; Folb, Naomi; Georgeu-Pepper, Daniella; Selohilwe, One; Petrus, Ruwayda; Mntambo, Ntokozo; Bhana, Arvin; Lombard, Carl; Bachmann, Max; Lund, Crick; Hanass-Hancock, Jill; Chisholm, Daniel; McCrone, Paul; Carmona, Sergio; Gaziano, Thomas; Levitt, Naomi; Kathree, Tasneem; Thornicroft, Graham
Background The scale-up of antiretroviral treatment (ART) programmes has seen HIV/AIDS transition to a chronic condition characterised by high rates of comorbidity with tuberculosis, non-communicable diseases (NCDs) and mental health disorders. Depression is one such disorder that is associated with higher rates of non-adherence, progression to AIDS and greater mortality. Detection and treatment of comorbid depression is critical to achieve viral load suppression in more than 90% of those on ART and is in line with the recent 90-90-90 Joint United Nations Programme on HIV/AIDS (UNAIDS) targets. The CobALT trial aims to provide evidence on the effectiveness and cost-effectiveness of scalable interventions to reduce the treatment gap posed by the growing burden of depression among adults on lifelong ART. Methods The study design is a pragmatic, parallel group, stratified, cluster randomised trial in 40 clinics across two rural districts of the North West Province of South Africa. The unit of randomisation is the clinic, with outcomes measured among 2000 patients on ART who screen positive for depression using the Patient Health Questionnaire (PHQ-9). Control group clinics are implementing the South African Department of Health’s Integrated Clinical Services Management model, which aims to reduce fragmentation of care in the context of rising multimorbidity, and which includes training in the Primary Care 101 (PC101) guide covering communicable diseases, NCDs, women’s health and mental disorders. In intervention clinics, we supplemented this with training specifically in the mental health components of PC101 and clinical communications skills training to support nurse-led chronic care. We strengthened the referral pathways through the introduction of a clinic-based behavioural health counsellor equipped to provide manualised depression counselling (eight sessions, individual or group), as well as adherence counselling sessions (one session, individual). The co-primary patient outcomes are a reduction in PHQ-9 scores of at least 50% from baseline and viral load suppression rates measured at 6 and 12 months, respectively. Discussion The trial will provide real-world effectiveness of case detection and collaborative care for depression including facility-based counselling on the mental and physical outcomes for people on lifelong ART in resource-constrained settings. Trial registration ClinicalTrials.gov ( NCT02407691 ) registered on 19 March 2015; Pan African Clinical Trials Registry ( 201504001078347 ) registered on 19/03/2015; South African National Clinical Trials Register (SANCTR) ( DOH-27-0515-5048 ) NHREC number 4048 issued on 21/04/2015.
Open Access
Detectable HIV-1 in semen in individuals with very low blood viral loads
(2020-03-05) Kariuki, Samuel M; Selhorst, Philippe; Norman, Jennifer; Cohen, Karen; Rebe, Kevin; Williamson, Carolyn; Dorfman, Jeffrey R
Abstract Background Several reports indicate that a portion (5–10%) of men living with HIV-1 intermittently shed HIV-1 RNA into seminal plasma while on long term effective antiretroviral therapy (ART). This is highly suggestive of an HIV-1 reservoir in the male genital tract. However, the status of this reservoir in men living with HIV-1 who are not under treatment is underexplored and has implications for understanding the origins and evolution of the reservoir. Finding Forty-three HIV-1 positive, antiretroviral therapy naïve study participants attending a men’s health clinic were studied. Semen viral loads and blood viral loads were generally correlated, with semen viral loads generally detected in individuals with blood viral loads > 10,000 cp/ml. However, we found 1 individual with undetectable viral loads (<20cp/ml) and 2 individuals with very low blood viral load (97 and 333cp/ml), but with detectable HIV-1 in semen (485–1157 copies/semen sample). Blood viral loads in the first individual were undetectable when tested three times over the prior 5 years. Conclusions Semen HIV-1 viral loads are usually related to blood viral loads, as we confirm. Nonetheless, this was not true in a substantial minority of individuals suggesting unexpectedly high levels of replication in the male genital tract in a few individuals, despite otherwise effective immune control. This may reflect establishment of a local reservoir of HIV-1 populations.
Open Access
Early and late direct costs in a Southern African antiretroviral treatment programme: a retrospective cohort analysis
(Public Library of Science, 2009) Leisegang, Rory; Cleary, Susan; Hislop, Michael; Davidse, Alistair; Regensberg, Leon; Little, Francesca; Maartens, Gary
Gary Maartens and colleagues describe the direct heath care costs and identify the drivers of cost over time in an HIV managed care program in Southern Africa.
Open Access
Effectiveness of patient adherence groups as a model of care for stable patients on antiretroviral therapy in Khayelitsha, Cape Town, South Africa
(Public Library of Science, 2013) Luque-Fernandez, Miguel Angel; Cutsem, Gilles Van; Goemaere, Eric; Hilderbrand, Katherine; Schomaker, Michael; Mantangana, Nompumelelo; Mathee, Shaheed; Dubula, Vuyiseka; Ford, Nathan; Hernán, Miguel A
BACKGROUND: Innovative models of care are required to cope with the ever-increasing number of patients on antiretroviral therapy in the most affected countries. This study, in Khayelitsha, South Africa, evaluates the effectiveness of a group-based model of care run predominantly by non-clinical staff in retaining patients in care and maintaining adherence. Methods and FINDINGS: Participation in "adherence clubs" was offered to adults who had been on ART for at least 18 months, had a current CD4 count >200 cells/ml and were virologically suppressed. Embedded in an ongoing cohort study, we compared loss to care and virologic rebound in patients receiving the intervention with patients attending routine nurse-led care from November 2007 to February 2011. We used inverse probability weighting to estimate the intention-to-treat effect of adherence club participation, adjusted for measured baseline and time-varying confounders. The principal outcome was the combination of death or loss to follow-up. The secondary outcome was virologic rebound in patients who were virologically suppressed at study entry. Of 2829 patients on ART for >18 months with a CD4 count above 200 cells/µl, 502 accepted club participation. At the end of the study, 97% of club patients remained in care compared with 85% of other patients. In adjusted analyses club participation reduced loss-to-care by 57% (hazard ratio [HR] 0.43, 95% CI = 0.21-0.91) and virologic rebound in patients who were initially suppressed by 67% (HR 0.33, 95% CI = 0.16-0.67). DISCUSSION: Patient adherence groups were found to be an effective model for improving retention and documented virologic suppression for stable patients in long term ART care. Out-of-clinic group-based models facilitated by non-clinical staff are a promising approach to assist in the long-term management of people on ART in high burden low or middle-income settings.
Open Access
Failure to eradicate Isospora belli diarrhoea despite immune reconstitution in adults with HIV--a case series
(Public Library of Science, 2012) Boyles, Tom H; Black, John; Meintjes, Graeme; Mendelson, Marc
Isospora belli causes diarrhoea in patients with AIDS. Most respond to targeted therapy and recommendations are that secondary prophylaxis can be stopped following immune reconstitution with ART. We report eight cases of chronic isosporiasis that persisted despite standard antimicrobial therapy, secondary prophylaxis, and good immunological and virological response to ART. Median CD4 nadir was 175.5 cells/mm 3 and median highest CD4 while symptomatic was 373 cells/mm 3 . Overall 34% of stool samples and 63% of duodenal biopsy specimens were positive for oocytes. Four patients died, two remain symptomatic and two recovered. Possible explanations for persistence of symptoms include host factors such as antigen specific immune deficiency or generalised reduction in gut immunity. Parasite factors may include accumulating resistance to co-trimoxazole. Research is required to determine the optimum dose and duration of co-trimoxazole therapy and whether dual therapy may be necessary. Mortality was high and pending more data we recommend extended treatment with high-dose co-trimoxazole in similar cases.
Open Access
Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study
(Public Library of Science, 2012) Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
Open Access
Hepatitis B infection, viral load and resistance in HIV-infected patients in Mozambique and Zambia
(Public Library of Science, 2016) Wandeler, Gilles; Musukuma, Kalo; Zürcher, Samuel; Vinikoor, Michael J; Llenas-García, Jara; Aly, Mussa M; Mulenga, Lloyd; Chi, Benjamin H; Ehmer, Jochen; Hobbins, Michael A; Bolton-Moore, Carolyn; Hoffmann, Christopher J; Egger, Matthias; IeDEA-Southern Africa
BACKGROUND: Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa. METHODS: We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy (ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine ® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression. RESULTS: Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval [CI]: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir. CONCLUSION: One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.
Open Access
Increased alpha-9 human papillomavirus species viral load in human immunodeficiency virus positive women
(2014-01-31) Mbulawa, Zizipho Z; Johnson, Leigh F; Marais, Dianne J; Gustavsson, Inger; Moodley, Jennifer R; Coetzee, David; Gyllensten, Ulf; Williamson, Anna-Lise
Abstract Background Persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR-HPV viral load are associated with the development of cancer. This study investigated the effect of human immunodeficiency virus (HIV) co-infection, HIV viral load and CD4 count on the HR-HPV viral load; and also investigated the predictors of cervical abnormalities. Methods Participants were 292 HIV-negative and 258 HIV-positive women. HR-HPV viral loads in cervical cells were determined by the real-time polymerase chain reaction. Results HIV-positive women had a significantly higher viral load for combined alpha-9 HPV species compared to HIV-negative women (median 3.9 copies per cell compared to 0.63 copies per cell, P = 0.022). This was not observed for individual HPV types. HIV-positive women with CD4 counts >350/μl had significantly lower viral loads for alpha-7 HPV species (median 0.12 copies per cell) than HIV-positive women with CD4 ≤350/μl (median 1.52 copies per cell, P = 0.008), but low CD4 count was not significantly associated with increased viral load for other HPV species. High viral loads for alpha-6, alpha-7 and alpha-9 HPV species were significant predictors of abnormal cytology in women. Conclusion HIV co-infection significantly increased the combined alpha-9 HPV viral load in women but not viral loads for individual HPV types. High HR-HPV viral load was associated with cervical abnormal cytology.
Open Access
Increasing transfers-out from an antiretroviral treatment service in South Africa: patient characteristics and rates of virological non-suppression
(Public Library of Science, 2013) Nglazi, Mweete D; Kaplan, Richard; Orrell, Catherine; Myer, Landon; Wood, Robin; Bekker, Linda-Gail; Lawn, Stephen D
Objectives: To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township. METHODS: This retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors. RESULTS: 4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively. CONCLUSIONS: With scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer.
Open Access
Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection
(Public Library of Science, 2009) Moore, Penny L; Ranchobe, Nthabeleng; Lambson, Bronwen E; Gray, Elin S; Cave, Eleanor; Abrahams, Melissa-Rose; Bandawe, Gama; Mlisana, Koleka; Karim, Salim S Abdool; Williamson, Carolyn
Author Summary Most HIV-1 infected individuals develop neutralizing antibodies against their own virus, termed an autologous neutralizing response. It is known that this response exerts pressure on the envelope of HIV, the target of such antibodies, resulting in neutralization escape. Here we have identified the targets of these antibodies and the precise genetic basis of neutralization escape in 4 individuals infected with HIV-1 subtype C. We show that V1V2 is commonly involved in escape, and that the C3 region is also a target in some cases. The latter observation confirms this region is exposed in subtype C, unlike subtype B. We show that neutralization escape is conferred by a few amino acid mutations, some of which are outside the antibody target site. Moreover, escape from these limited specificities even within a single individual occurs via a variety of different pathways involving substitutions, indels and glycan shifts. The finding in 2 individuals that an anti-C3 response developed first, followed by an anti-V1V2 response, suggests there may be specific regions of envelope particularly vulnerable to antibody neutralization. Overall, we propose a mechanistic explanation for how HIV-1 epitopes drive sequential waves of neutralization escape in early subtype C infection.
Open Access
Low prevalence of liver disease but regional differences in HBV treatment characteristics mark HIV/HBV co-infection in a South African HIV clinical trial
(Public Library of Science, 2013) Ive, Prudence; MacLeod, William; Mkumla, Nompumelelo; Orrell, Catherine; Jentsch, Ute; Wallis, Carole L; Stevens, Wendy; Wood, Robin; Sanne, Ian; Bhattacharya, Debika
BACKGROUND: Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA 'Safeguard the household study' in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation. METHODS: 812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline. RESULTS: Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3-4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007). CONCLUSION: One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.
Open Access
Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study
(Public Library of Science, 2013) Estill, Janne; Egger, Matthias; Johnson, Leigh F; Gsponer, Thomas; Wandeler, Gilles; Davies, Mary-Ann; Boulle, Andrew; Wood, Robin; Garone, Daniela; Stringer, Jeffrey S A
Objectives Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. Design: Mathematical modelling study based on data from ART programmes. METHODS: We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. RESULTS: RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. CONCLUSIONS: VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.
Open Access
Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies
(Public Library of Science, 2014) Boulle, Andrew; Schomaker, Michael; May, Margaret T; Hogg, Robert S; Shepherd, Bryan E; Monge, Susana; Keiser, Olivia; Lampe, Fiona C; Giddy, Janet; Ndirangu, James
Analyzing survival in HIV treatment cohorts, Andrew Boulle and colleagues find mortality rates in South Africa comparable to or better than those in North America by 4 years after starting antiretroviral therapy. Please see later in the article for the Editors' Summary
Open Access
Not all are lost: interrupted laboratory monitoring, early death, and loss to follow-up (LTFU) in a large South African treatment program
(Public Library of Science, 2012) Ahonkhai, Aima A; Noubary, Farzad; Munro, Alison; Stark, Ruth; Wilke, Marisa; Freedberg, Kenneth A; Wood, Robin; Losina, Elena
BACKGROUND: Many HIV treatment programs in resource-limited settings are plagued by high rates of loss to follow-up (LTFU). Most studies have not distinguished between those who briefly interrupt, but return to care, and those more chronically lost to follow-up. METHODS: We conducted a retrospective cohort study of 11,397 adults initiating antiretroviral therapy (ART) in 71 Southern African Catholic Bishops Conference/Catholic Relief Services HIV treatment clinics between January 2004 and December 2008. We distinguished among patients with early death, within the first 7 months on ART; patients with interruptions in laboratory monitoring (ILM), defined as missing visits in the first 7 months on ART, but returning to care by 12 months; and those LTFU, defined as missing all follow-up visits in the first 12 months on ART. We used multilevel logistic regression models to determine patient and clinic-level characteristics associated with these outcomes. RESULTS: In the first year on ART, 60% of patients remained in care, 30% missed laboratory visits, and 10% suffered early death. Of the 3,194 patients who missed laboratory visits, 40% had ILM, resuming care by 12 months. After 12 months on ART, patients with ILM had a 30% increase in detectable viremia compared to those who remained in care. Risk of LTFU decreased with increasing enrollment year, and was lowest for patients who enrolled in 2008 compared to 2004 [OR 0.49, 95%CI 0.39-0.62]. CONCLUSIONS: In a large community-based cohort in South Africa, nearly 30% of patients miss follow-up visits for CD4 monitoring in the first year after starting ART. Of those, 40% have ILM but return to clinic with worse virologic outcomes than those who remain in care. The risk of chronic LTFU decreased with enrollment year. As ART availability increases, interruptions in care may become more common, and should be accounted for in addressing program LTFU.
Open Access
A novel diagnostic target in the hepatitis C virus genome
(Public Library of Science, 2009) Drexler, Jan Felix; Kupfer, Bernd; Petersen, Nadine; Grotto, Rejane Maria Tommasini; Rodrigues, Silvia Maria Corvino; Grywna, Klaus; Panning, Marcus; Annan, Augustina; Silva, Giovanni Faria; Douglas, Jill
Christian Drosten and colleagues develop, validate, and make openly available a prototype hepatitis C virus assay based on the conserved 3' X-tail element, with potential for clinical use in developing countries.