PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (1143298)

Clipboard (0)
None

Related Articles

1.  The Effect of Highly Active Antiretroviral Therapy on the Survival of HIV-Infected Children in a Resource-Deprived Setting: A Cohort Study 
PLoS Medicine  2011;8(6):e1001044.
This observational cohort study by Andrew Edmonds and colleagues reports that treatment with highly active antiretroviral therapy (HAART) markedly improves the survival of HIV-infected children in Kinshasa, DRC, a resource-deprived setting.
Background
The effect of highly active antiretroviral therapy (HAART) on the survival of HIV-infected children has not been well quantified. Because most pediatric HIV occurs in low- and middle-income countries, our objective was to provide a first estimate of this effect among children living in a resource-deprived setting.
Methods and Findings
Observational data from HAART-naïve children enrolled into an HIV care and treatment program in Kinshasa, Democratic Republic of the Congo, between December 2004 and May 2010 were analyzed. We used marginal structural models to estimate the effect of HAART on survival while accounting for time-dependent confounders affected by exposure. At the start of follow-up, the median age of the 790 children was 5.9 y, 528 (66.8%) had advanced or severe immunodeficiency, and 405 (51.3%) were in HIV clinical stage 3 or 4. The children were observed for a median of 31.2 mo and contributed a total of 2,089.8 person-years. Eighty children (10.1%) died, 619 (78.4%) initiated HAART, six (0.8%) transferred to a different care provider, and 76 (9.6%) were lost to follow-up. The mortality rate was 3.2 deaths per 100 person-years (95% confidence interval [CI] 2.4–4.2) during receipt of HAART and 6.0 deaths per 100 person-years (95% CI 4.1–8.6) during receipt of primary HIV care only. The mortality hazard ratio comparing HAART with no HAART from a marginal structural model was 0.25 (95% CI 0.06–0.95).
Conclusions
HAART reduced the hazard of mortality in HIV-infected children in Kinshasa by 75%, an estimate that is similar in magnitude but with lower precision than the reported effect of HAART on survival among children in the United States.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2009, an estimated 2.5 million children were living with HIV, the majority of whom (2.3 million) were in sub-Saharan Africa. Most (90%) of these children acquired HIV from their HIV-infected mothers during pregnancy, birth, or breastfeeding, highlighting the importance of giving effective drugs for the prevention of mother to child transmission. As such interventions are still not widely accessible or available in most resource-limited countries, where the burden of HIV is highest, every day an estimated 1,000 children were newly infected with HIV in 2009, but only 360,000 children were receiving highly active antiretroviral therapy (HAART).
Although HAART improves the survival of adults living with HIV, less is known about the degree to which HAART affects the survival of HIV-infected children—although response to antiretroviral treatment is known to differ across age groups. Furthermore, as the course of HIV disease in children is different from that in adults (partly because of the impact of the virus on the immature thymus, which can lead to high HIV RNA viremia and rapid death), it is inappropriate to extrapolate results from studies of adults to pediatric populations. Therefore, it is imperative that the effect of HAART on survival be quantified specifically in children.
Why Was This Study Done?
Most observational studies of the effects of treatment on child survival have been undertaken in high-income countries, such as Italy and the United States. As most children with HIV live in low-resource areas, where multiple factors, such as delayed presentation to care and a higher incidence of co-occurring conditions, might adversely affect treatment outcomes, there is a specific need for information on the effects of HAART in children with HIV living in low-income countries. Although some investigations have taken place in pediatric cohorts from such countries (for example, Côte d'Ivoire, Haiti, Lesotho, Thailand, and Zambia), the effect of HAART on mortality has not been accurately quantified among children in a resource-deprived setting. Therefore, in this observational clinical cohort study, the researchers investigated the effect of HAART on mortality in HIV-infected children in Kinshasa, in the Democratic Republic of the Congo (DRC).
What Did the Researchers Do and Find?
The researchers analyzed data from 790 children enrolled into an HIV program in Kinshasa, DRC, between December 2004 and May 2010 and used a statistical model (marginal structural models) to adjust for time-dependent confounding factors, such as the fact that HAART is typically initiated in sicker patients, for example, those with lower CD4 cell percentages. Assuming that all children starting HAART received it uninterruptedly throughout follow-up, using this statistical model, the researchers were able to compare the hazard ratio of death had all children initiated HAART to that had no children initiated HAART during follow-up.
In the study, 619 out of the 790 children (78.4%) initiated HAART during follow-up and were followed for a median of 31.2 months, with a median of 30 HIV care visits. Of those who started treatment, 110 (17.8%) switched to an alternative regimen because of an adverse event or treatment failure. During the 2,089.8 accrued person-years of follow-up, 80 children (10.1%) died, giving an overall mortality rate of 3.8 deaths per 100 person-years. The unadjusted mortality rate ratio comparing HAART to no HAART was 0.54. Using a marginal structural model, the researchers estimated that compared to no HAART, HAART reduced the hazard (rate) of mortality during follow-up by 75%.
What Do These Findings Mean?
These findings show that treatment with HAART markedly improved the survival of children infected with HIV in Kinshasa, DRC, and suggest that HAART is as effective in improving the survival of HIV-infected children in a severely resource-deprived country (still recovering from civil war) as in more resource-privileged settings—an important finding given that the vast majority of children receiving HAART live in resource-poor areas. This study provides additional evidence that accelerating rollout of antiretroviral therapy to children with HIV in resource-poor countries is lifesaving and effective. Future research needs to address how effective HAART is in understudied populations in resource-poor countries, such as undernourished children or those with co-infections such as tuberculosis.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001044.
The World Health Organization's Web site has more information about the treatment of children living with HIV
Médecins Sans Frontières's Campaign for Access to Essential Medicines Web site has more information on pediatric HAART
doi:10.1371/journal.pmed.1001044
PMCID: PMC3114869  PMID: 21695087
2.  Antiretroviral Treatment and Prevention of Peripartum and Postnatal HIV Transmission in West Africa: Evaluation of a Two-Tiered Approach 
PLoS Medicine  2007;4(8):e257.
Background
Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
Methods and Findings
The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged ≥ 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%–4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%–9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%–7.0%) at age week 4 wk and 11.7% (95% CI 7.5%–15.9%) at 12 mo.
Conclusions
This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health.
In an observational cohort study from Côte d'Ivoire, François Dabis and colleagues report on prevention of mother-to-child HIV transmission among women receiving antiretroviral therapy according to World Health Organization recommendations.
Editors' Summary
Background
Effective treatments are available to prevent AIDS in people who are infected with HIV, but not everyone with HIV needs to take medication. Usually, anti-HIV medication is recommended only for those whose immune systems have been significantly affected by the virus, as evidenced by symptoms or by the results of a blood test, the CD4 lymphocyte (“T cell”) count. Treating HIV usually requires a combination of three or more medications. These combinations (called HAART) must be taken every day, can cause complications, and can be expensive.
Worldwide, more than half a million children became infected with HIV each year. Most of these children acquire HIV from their mothers during pregnancy or around the time of birth. If a pregnant woman with HIV takes HAART, her chances of passing HIV to the baby are greatly reduced, but the possible side effects of HAART on the baby are not known. Also, most transmission of HIV from mothers to babies occurs in poor countries where supplies of HAART are limited. For these reasons, World Health Organization (WHO) does not recommend that every pregnant woman receive HAART to prevent HIV transmission to the baby, unless the woman needs HAART for her own health (for example if her T cells are low or she has severe symptoms of HIV infection). For pregnant women with HIV who do not need to take HAART for their own health, less complicated treatments, involving a short course of one or two HIV drugs, can be used to reduce the risk of passing HIV to the baby.
Why Was This Study Done?
The WHO recommendations for HAART in pregnancy are based on the best available evidence, but it is important to know how well they work in actual practice. The authors of this study were providing HIV treatment to pregnant women with HIV in West Africa through an established clinic program in Abidjan, Côte d'Ivoire, and wanted to see how well the WHO recommendations for HAART or short-course treatments, depending on the mother's condition, were working to protect babies from HIV infection.
What Did the Researchers Do and Find?
The researchers studied 250 HIV-infected pregnant women who received HIV medications in the Abidjan program between mid-2003 and mid-2005. In accordance with WHO guidelines, 107 women began HAART for their own health during pregnancy, and 143 women did not qualify for HAART but received other short course treatments (scARV) to prevent HIV transmission to their babies. The authors monitored mothers and babies for treatment side effects and tested the babies for HIV infection up to age 1 y.
They found that HAART was relatively safe during pregnancy, although babies born to women on HAART were more likely (26.3%) to have low birth weight than babies born to women who received scARV (12.4%). Also, 7.5% of women on HAART developed side effects requiring a change in their medications. Combining the results from HAART and scART groups, the chance of HIV transmission around the time of birth was 2.2%, increasing to 5.7% at age 1 y. (Three-quarters of the infants were breast-fed; safe water for mixing formula was not reliably available.) The study found no difference in risk of HIV infection between babies whose mothers received HAART and those whose mothers received scARV according to guidelines.
What Do These Findings Mean?
These results support the safety and effectiveness of the WHO two-tiered approach for preventing mother-to-child transmission. This study was not designed to compare HAART to scART directly, because the women who received HAART were the ones with more advanced HIV infection, which might have affected their babies in many ways.
Compared to earlier pregnancy studies of HAART in rich countries, this study of the WHO approach in West Africa showed similar success in protecting infants from HIV infection around the time of birth. Unfortunately, because formula feeding was not generally available in resource-limited settings, protection declined over the first year of life with breast-feeding, but some protection remained.
This study confirms that close monitoring of pregnant women on HAART is necessary, so that drugs can be changed if side effects develop. The study does not tell us whether using scARV in pregnancy might change the virus in ways that would make it more difficult to treat the same women with HAART later if they needed it. The reason for low birth weight in some babies born to mothers on HAART is unclear. It may be because the women who needed HAART had more severe health problems from their HIV, or it may be a result of the HAART itself.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040257.
World Health Organization has a page on prevention of mother-to-child transmission of HIV
“Women, Children, and HIV” is a resource site from the François Xavier Bagnoud Center and UCSF
The MTCT-Plus initiative at Columbia University supports the programs in Abidjan
doi:10.1371/journal.pmed.0040257
PMCID: PMC1949842  PMID: 17713983
3.  Effects of highly active antiretroviral therapy and its adherence on herpes zoster incidence: a longitudinal cohort study 
Background
Herpes zoster (HZ) is common among HIV-infected individuals, but the impacts of highly active antiretroviral therapy (HAART) and HAART adherence on HZ risk have not been well studied.
Methods
The effects of HAART and HAART adherence on HZ incidence were evaluated by comparing HIV-infected women on HAART (HAART use group) with the HIV-infected women remaining HAART naïve (HAART naïve group) in the Women’s Interagency HIV Study (WIHS). A 1:1 matching with propensity score for predicting HAART initiation was conducted to balance background covariates at index visit, including HIV disease stage. Kaplan-Meier method was used to compare the risk of HZ development between the matched pairs. Cox proportional hazard models were used to assess the effects of HAART and HAART adherence on HZ incidence.
Results
Through propensity score matching, 389 pairs of participants were identified and they contributed 3,909 person years after matching. The background covariates were similar between the matched pairs at the index visit. The participants had a mean age around 39 years old, and about 61% of them were Black and 22% were Latina. No significant difference in HZ risk was observed between the HAART use group and the HAART naïve group during the first year of follow-up in any analyses. In the univariate analysis, the HAART use group had marginally lower HZ risk (Hazard Ratio (HR): 0.72; 95% Confidence Interval (CI): 0.48-1.1) over the entire follow-up period. However, women with a HAART adherence level of ≥95% had significantly lower HZ risk (HR: 0.54; 95% CI: 0.31, 0.94) compared to the HAART naïve women. The association remained significant after adjusting for quality of life score and acyclovir use, but it attenuated and was no longer statistically significant after adjusting for an intermediate variable, either CD4+ T cell counts or HIV viral load.
Conclusions
Among adult women, we observed a significant preventive effect of long-term HAART use on HZ incidence when a HAART adherence level of ≥95% was attained, and this effect was mediated through reduction of HIV viral load and improvement of CD4+ T cell counts.
doi:10.1186/1742-6405-10-34
PMCID: PMC3904465  PMID: 24373482
HAART; Adherence; Herpes zoster; Incidence; Propensity score
4.  Effectiveness of option B highly active antiretroviral therapy (HAART) prevention of mother-to-child transmission (PMTCT) in pregnant HIV women 
BMC Research Notes  2014;7:52.
Background
Ensuring that no baby is born with HIV is an essential step towards achieving an AIDS-free generation. To achieve this, strategies that decouple links between childbirth and HIV transmission are necessary. Traditional forms of prevention of mother-to-child transmission of HIV (PMTCT), has been recommended. Recognizing the importance and challenges of combination of methods to achieve rapid PMTCT, the World Health Organization (WHO) recommended option B Highly Active Antiretroviral Therapy (HAART) for all HIV-positive pregnant women. This study aimed to evaluate the effectiveness of the HAART in PMTCT. A cohort of HIV-infected pregnant women in Kenya were obtained from the DREAM Center, Nairobi. The study participants underwent adherence counselling and Option B of HAART [Nevirapine(NVP) + Lamivudine + Zidovudine] at the fourth week of gestation followed by an intravenous NVP administration intrapartum and postpartum NVP syrup to the respective infants for six weeks. Absolute pre-HAART and post-HAART CD4 counts and viral loads counts were determined. Comparison of the CD4 counts and viral loads before and after administration of HAART were done using Wilcoxon’s Matched Pairs Signed-Ranks Test.
Findings
The mean absolute CD4 cell counts in mothers after administration of HAART was significantly higher (Z = 15.664, p < 0.001) than before the administration of HAART). Also the viral load of the mothers significantly (Z = 11.324, p < 0.001) reduced following HAART treatment. Following the HAART administration in mothers, up to 90% of children were confirmed to be HIV negative.
Conclusion
Administration of HAART to mothers and children demonstrated an effective mechanism of PMTCT. However, other aspects of HAART such as adherence, costs, mothers behaviour during HAART, and the child feeding programme during the therapy should further be evaluated and ascertained how they can affect the overall efficacy of option B HAART in PMTCT.
doi:10.1186/1756-0500-7-52
PMCID: PMC3898637  PMID: 24447387
Antiretroviral; CD4 counts; Early Infant Diagnosis; Highly Active Antiretroviral Therapy (HAART); Mother-To-Child Transmission (MTCT); Prevention of Mother-To-Child Transmission (PMTCT)
5.  Emergence of Drug Resistance Is Associated with an Increased Risk of Death among Patients First Starting HAART 
PLoS Medicine  2006;3(9):e356.
Background
The impact of the emergence of drug-resistance mutations on mortality is not well characterized in antiretroviral-naïve patients first starting highly active antiretroviral therapy (HAART). Patients may be able to sustain immunologic function with resistant virus, and there is limited evidence that reduced sensitivity to antiretrovirals leads to rapid disease progression or death. We undertook the present analysis to characterize the determinants of mortality in a prospective cohort study with a median of nearly 5 y of follow-up. The objective of this study was to determine the impact of the emergence of drug-resistance mutations on survival among persons initiating HAART.
Methods and Findings
Participants were antiretroviral therapy naïve at entry and initiated triple combination antiretroviral therapy between August 1, 1996, and September 30, 1999. Marginal structural modeling was used to address potential confounding between time-dependent variables in the Cox proportional hazard regression models. In this analysis resistance to any class of drug was considered as a binary time-dependent exposure to the risk of death, controlling for the effect of other time-dependent confounders. We also considered each separate class of mutation as a binary time-dependent exposure, while controlling for the presence/absence of other mutations. A total of 207 deaths were identified among 1,138 participants over the follow-up period, with an all cause mortality rate of 18.2%. Among the 679 patients with HIV-drug-resistance genotyping done before initiating HAART, HIV-drug resistance to any class was observed in 53 (7.8%) of the patients. During follow-up, HIV-drug resistance to any class was observed in 302 (26.5%) participants. Emergence of any resistance was associated with mortality (hazard ratio: 1.75 [95% confidence interval: 1.27, 2.43]). When we considered each class of resistance separately, persons who exhibited resistance to non-nucleoside reverse transcriptase inhibitors had the highest risk: mortality rates were 3.02 times higher (95% confidence interval: 1.99, 4.57) for these patients than for those who did not exhibit this type of resistance.
Conclusions
We demonstrated that emergence of resistance to non-nucleoside reverse transcriptase inhibitors was associated with a greater risk of subsequent death than was emergence of protease inhibitor resistance. Future research is needed to identify the particular subpopulations of men and women at greatest risk and to elucidate the impact of resistance over a longer follow-up period.
Emergence of resistance to both non-nucleoside reverse transcriptase inhibitors and protease inhibitors was associated with a higher risk of subsequent death, but the risk was greater in patients with NNRTI-resistant HIV.
Editors' Summary
Background.
In the 1980s, infection with the human immunodeficiency virus (HIV) was effectively a death sentence. HIV causes AIDS (acquired immunodeficiency syndrome) by replicating inside immune system cells and destroying them, which leaves infected individuals unable to fight off other viruses and bacteria. The first antiretroviral drugs were developed quickly, but it soon became clear that single antiretrovirals only transiently suppress HIV infection. HIV mutates (accumulates random changes to its genetic material) very rapidly and, although most of these changes (or mutations) are bad for the virus, by chance some make it drug resistant. Highly active antiretroviral therapy (HAART), which was introduced in the mid-1990s, combines three or four antiretroviral drugs that act at different stages of the viral life cycle. For example, they inhibit the reverse transcriptase that the virus uses to replicate its genetic material, or the protease that is necessary to assemble new viruses. With HAART, the replication of any virus that develops resistance to one drug is inhibited by the other drugs in the mix. As a consequence, for many individuals with access to HAART, AIDS has become a chronic rather than a fatal disease. However, being on HAART requires patients to take several pills a day at specific times. In addition, the drugs in the HAART regimens often have side effects.
Why Was This Study Done?
Drug resistance still develops even with HAART, often because patients don't stick to the complicated regimens. The detection of resistance to one drug is usually the prompt to change a patient's drug regimen to head off possible treatment failure. Although most patients treated with HAART live for many years, some still die from AIDS. We don't know much about how the emergence of drug-resistance mutations affects mortality in patients who are starting antiretroviral therapy for the first time. In this study, the researchers looked at how the emergence of drug resistance affected survival in a group of HIV/AIDS patients in British Columbia, Canada. Here, everyone with HIV/AIDS has access to free medical attention, HAART, and laboratory monitoring, and full details of all HAART recipients are entered into a central reporting system.
What Did the Researchers Do and Find?
The researchers enrolled people who started antiretroviral therapy for the first time between August 1996 and September 1999 into the HAART Observational Medical Evaluation and Research (HOMER) cohort. They then excluded anyone who was infected with already drug-resistant HIV strains (based on the presence of drug-resistance mutations in viruses isolated from the patients) at the start of therapy. The remaining 1,138 patients were followed for an average of five years. All the patients received either two nucleoside reverse transcriptase inhibitors and a protease inhibitor, or two nucleoside and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Nearly a fifth of the study participants died during the follow-up period. Most of these patients actually had drug-sensitive viruses, possibly because they had neglected taking their drugs to such an extent that there had been insufficient drug exposure to select for drug-resistant viruses. In a quarter of the patients, however, HIV strains resistant to one or more antiretroviral drugs emerged during the study (again judged by looking for mutations). Detailed statistical analyses indicated that the emergence of any drug resistance nearly doubled the risk of patients dying, and that people carrying viruses resistant to NNRTIs were three times as likely to die as those without resistance to this class of antiretroviral drug.
What Do These Findings Mean?
These results provide new information about the emergence of drug-resistant HIV during HAART and possible effects on the long-term survival of patients. In particular, they suggest that clinicians should watch carefully for the emergence of resistance to NNRTIs in their patients. Because this type of resistance is often due to poor adherence to drug regimens, these results also suggest that increased efforts should be made to ensure that patients comply with the prescribed HAART regimens, especially those whose antiretroviral therapy includes NNRTIs. As with all studies in which a group of individuals who share a common characteristic are studied over time, it is possible that some other, unmeasured difference between the patients who died and those who didn't—rather than emerging drug resistance—is responsible for the observed differences in survival. Additional studies are needed to confirm the findings here, and to investigate whether specific subpopulations of patients are at particular risk of developing drug resistance and/or dying during HAART.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030356.
US National Institute of Allergy and Infectious Diseases fact sheet on HIV infection and AIDS
US Department of Health and Human Services information on AIDS, including details of approved drugs for the treatment of HIV infection
US Centers for Disease Control and Prevention information on HIV/AIDS
Aidsmap, information on HIV and AIDS provided by the charity NAM, which includes details on antiretroviral drugs
doi:10.1371/journal.pmed.0030356
PMCID: PMC1569883  PMID: 16984218
6.  Association of CD4+ T-lymphocyte counts and new thymic emigrants in HIV-infected children during successful highly active antiretroviral therapy 
Background
In a cohort of children receiving highly active antiretroviral therapy (HAART) with sustained plasma HIV-1 RNA < 50 copies/mL, children who reached undetectable RNA after week 8 (slow responders, median: week 20) had higher HIV-1 intracellular DNA (HIV-1 DNA) and equal or greater CD4+ T-lymphocyte counts compared with children who reached undetectable plasma HIV-1 RNA by week 8 (rapid responders) throughout HAART.
Objective
To determine whether levels of T-cell receptor excision circles (TRECs) could explain the apparent inconsistency between the quantity of HIV-1 DNA and CD4+ T-lymphocyte counts in HIV-1–infected children receiving HAART with sustained virologic suppression.
Methods
T-cell receptor excision circles and HIV-1 DNA and plasma HIV-1 RNA were quantified longitudinally by PCR in 31 children (median age, 5.6 years) with sustained undetectable plasma HIV-1 RNA for >104 weeks of HAART.
Results
There was a positive correlation between TREC and HIV-1 DNA during HAART, notably at weeks 48 and 80 (P < .004). During the early stage of HAART, TREC levels positively correlated with CD4+ T-lymphocyte percentages (P < .02) and naive CD4+ T-lymphocyte counts (P < .001) and percentages (P = .05). Median TREC levels were consistently equal or higher in slow responders compared with rapid responders (P < .001) despite slow responders having consistently greater quantities of HIV-1 DNA.
Conclusion
To maintain adequate levels of CD4+ T-lymphocytes, children with high HIV-1 DNA maintain high levels of TREC while receiving HAART. Thus, a thymic control mechanism is required to maintain new CD4+ T lymphocytes in the presence of persistent virus.
Clinical implications
The TREC level is a useful marker of thymic function in HIV-infected children.
doi:10.1016/j.jaci.2006.01.013
PMCID: PMC2756961  PMID: 16630951
T-cell receptor excision circles; immune reconstitution; HIV-1 intracellular DNA; CD4+ T lymphocytes; HAART; children
7.  Public-Health and Individual Approaches to Antiretroviral Therapy: Township South Africa and Switzerland Compared 
PLoS Medicine  2008;5(7):e148.
Background
The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland.
Methods and Findings
We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/μl in South Africa and 204 cells/μl in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%–97%) in South Africa and 96% (94%–97%) in Switzerland, and 26% (22%–29%) and 27% (24%–31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81–19.2) during months 1–3 and 1.77 (0.90–3.50) during months 4–24.
Conclusions
Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
Comparing HIV treatment in Switzerland, where drug selection is individualized, and South Africa, where a programmatic approach is used, Matthias Egger and colleagues find similar virologic outcomes over two years.
Editors' Summary
Background.
Acquired immunodeficiency syndrome (AIDS) has killed more than 25 million people since the first reported case in 1981, and more than 30 million people are now infected with the human immunodeficiency virus (HIV), which causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of becoming infected. Then, in 1996, highly active antiretroviral therapy (HAART)—a combination of several antiretroviral drugs—was developed. Now, in resource-rich countries, clinicians provide individually tailored care for HIV-infected people by prescribing combinations of antiretroviral drugs chosen from more than 20 approved medicines. The approach to treatment of HIV in developed countries typically also includes frequent monitoring of the amount of virus in patients' blood (viral load), viral resistance testing (to see whether any viruses are resistant to specific antiretroviral drugs), and regular CD4 cell counts (an indication of immune-system health). Since the implementation of these interventions, the health and life expectancy of people with HIV has improved dramatically in these countries.
Why Was This Study Done?
The history of HIV care in resource-poor countries has been very different. Initially, these countries could not afford to provide HAART for their populations. In 2003, however, governments, international agencies, and funding bodies began to implement plans to increase HAART coverage in developing countries. By December 2006, more than a quarter of the HIV-infected people in low- and middle-income countries who urgently needed treatment were receiving HAART. However, instead of individualized treatment, HAART programs in developing countries follow a public-health approach developed by the World Health Organization. That is, drug regimens, clinical decision-making, and clinical and laboratory monitoring are all standardized. This public-health approach takes into account the realities of under-resourced health systems, but is it as effective as the individualized approach? The researchers addressed this question by comparing virologic responses (the effect of treatment on the viral load), changes to first-line (initial) therapy, and deaths in patients receiving HAART in South Africa (public-health approach) and in Switzerland (individualized approach).
What Did the Researchers Do and Find?
The researchers analyzed data collected since 2001 from more than 2,000 patients enrolled in HAART programs in two townships (Gugulethu and Khayelitsha) in Cape Town, South Africa, and from more than 1,000 patients enrolled in the Swiss HIV Cohort Study, a nationwide study of HIV-infected people. The patients in South Africa, who had a lower starting CD4 cell count and were more likely to have advanced AIDS than the patients in Switzerland, started their treatment for HIV infection with one of four first-line therapies, and about a quarter changed to a second-line therapy during the study. By contrast, 36 first-line regimens were used in Switzerland and half the patients changed to a different regimen. Despite these differences, the viral load was greatly reduced within a year in virtually all the patients and viral rebound (an increased viral load after a low measurement) developed within 2 years in a quarter of the patients in both countries. However, more patients died in South Africa than in Switzerland, particularly during the first 3 months of therapy.
What Do These Findings Mean?
These findings suggest that the public-health approach to HAART practiced in South Africa is as effective in terms of virologic outcomes as the individualized approach practiced in Switzerland. This is reassuring because it suggests that “antiretroviral anarchy” (the unregulated use of antiretroviral drugs, interruptions in drug supplies, and the lack of treatment monitoring), which is likely to lead to the emergence of viral resistance, is not happening in South Africa as some experts feared it might. Thus, these findings support the continued rollout of the public-health approach to HAART in resource-poor countries. Conversely, they also suggest that a more standardized approach to HAART could be taken in Switzerland (and in other industrialized countries) without compromising its effectiveness. Finally, the higher mortality in South Africa than in Switzerland, which partly reflects the many patients in South Africa in desperate need of HAART and their more advanced disease at the start of therapy, suggests that HIV-infected patients in South Africa and in other resource-limited countries would benefit from earlier initiation of therapy.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050148.
The World Health Organization provides information about universal access to HIV treatment (in several languages) and on its recommendations for a public-health approach to antiretroviral therapy for HIV infection
More details on the Swiss HIV Cohort Study and on the studies in Gugulethu and Khayelitsha are available
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS, including detailed information about antiretroviral therapy and links to treatment guidelines for various countries
Information is available from Avert, an international AIDS charity, on HIV and AIDS around the world and on providing AIDS drug treatment for millions
doi:10.1371/journal.pmed.0050148
PMCID: PMC2443185  PMID: 18613745
8.  Kidney and liver organ transplantation in persons with human immunodeficiency virus 
Executive Summary
Objective
The objective of this analysis is to determine the effectiveness of solid organ transplantation in persons with end stage organ failure (ESOF) and human immunodeficiency virus (HIV+)
Clinical Need: Condition and Target Population
Patients with end stage organ failure who have been unresponsive to other forms of treatment eventually require solid organ transplantation. Similar to persons who are HIV negative (HIV−), persons living with HIV infection (HIV+) are at risk for ESOF from viral (e.g. hepatitis B and C) and non-viral aetiologies (e.g. coronary artery disease, diabetes, hepatocellular carcinoma). Additionally, HIV+ persons also incur risks of ESOF from HIV-associated nephropathy (HIVAN), accelerated liver damage from hepatitis C virus (HCV+), with which an estimated 30% of HIV positive (HIV+) persons are co-infected, and coronary artery disease secondary to antiretroviral therapy. Concerns that the need for post transplant immunosuppression and/or the interaction of immunosuppressive drugs with antiretroviral agents may accelerate the progression of HIV disease, as well as the risk of opportunistic infections post transplantation, have led to uncertainty regarding the overall benefit of transplantation among HIV+ patients. Moreover, the scarcity of donor organs and their use in a population where the clinical benefit of transplantation is uncertain has limited the availability of organ transplantation to persons living with ESOF and HIV.
With the development of highly active anti retroviral therapy (HAART), which has been available in Canada since 1997, there has been improved survival and health-related quality of life for persons living with HIV. HAART can suppress HIV replication, enhance immune function, and slow disease progression. HAART managed persons can now be expected to live longer than those in the pre-HAART era and as a result many will now experience ESOF well before they experience life-threatening conditions related to HIV infection. Given their improved prognosis and the burden of illness they may experience from ESOF, the benefit of solid organ transplantation for HIV+ patients needs to be reassessed.
Evidence-Based Analysis Methods
Research Questions
What are the effectiveness and cost effectiveness of solid organ transplantation in HIV+ persons with ESOF?
Literature Search
A literature search was performed on September 22, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1996 to September 22, 2009.
Inclusion Criteria
Systematic review with or without a Meta analysis, RCT, Non-RCT with controls
HIV+ population undergoing solid organ transplantation
HIV+ population managed with HAART therapy
Controls include persons undergoing solid organ transplantation who are i) HIV− ii) HCV+ mono-infected, and iii) HIV+ persons with ESOF not transplanted.
Studies that completed and reported results of a Kaplan-Meier Survival Curve analysis.
Studies with a minimum (mean or medium) follow up of 1-year.
English language citations
Exclusion Criteria
Case reports and case series were excluded form this review.
Outcomes of Interest
i) Risk of Death after transplantation
ii) Death censored graft survival (DCGS)
iii) HIV disease progression defined as the post transplant incidence of:
- opportunistic infections or neoplasms,
- CD4+ T-cell count < 200mm3, and
- any detectable level of plasma HIV viral load.
iv) Acute graft rejection,
v) Return to dialysis,
vi) Recurrence of HCV infection
Summary of Findings
No direct evidence comparing an HIV+ cohort undergoing transplantation with the same not undergoing transplantation (wait list) was found in the literature search.
The results of this review are reported for the following comparison cohorts undergoing transplantation:
i) Kidney Transplantation: HIV+ cohort compared with HIV− cohort
ii) Liver Transplantation: HIV+ cohort compared with HIV− negative cohort
iii) Liver Transplantation: HIV+ HCV+ (co-infected) cohort compared with HCV+ (mono-infected) cohort
Kidney Transplantation: HIV+ vs. HIV−
Based on a pooled HIV+ cohort sample size of 285 patients across four studies, the risk of death after kidney transplantation in an HIV+ cohort does not differ to that of an HIV− cohort [hazard ratio (HR): 0.90; 95% CI: 0.36, 2.23]. The quality of evidence supporting this outcome is very low.
Death censored graft survival was reported in one study with an HIV+ cohort sample size of 100, and was statistically significantly different (p=.03) to that in the HIV− cohort (n=36,492). However, the quality of evidence supporting this outcome was determined to be very low. There was also uncertainty in the rate of return to dialysis after kidney transplantation in both the HIV+ and HIV− groups and the effect, if any, this may have on patient survival. Because of the very low quality evidence rating, the effect of kidney transplantation on HIV-disease progression is uncertain.
The rate of acute graft rejection was determined using the data from one study. There was a nonsignificant difference between the HIV+ and HIV− cohorts (OR 0.13; 95% CI: 0.01, 2.64), although again, because of very low quality evidence there is uncertainty in this estimate of effect.
Liver Transplantation: HIV+ vs. HIV−
Based on a combined HIV+ cohort sample size of 198 patient across five studies, the risk of death after liver transplantation in an HIV+ cohort (with at least 50% of the cohort co-infected with HCV+) is statistically significantly 64% greater compared with an HIV− cohort (HR: 1.64; 95% CI: 1.32, 2.02). The quality of evidence supporting this outcome is very low.
Death censored graft survival was reported for an HIV+ cohort in one study (n=11) however the DCGS rate of the contemporaneous control HIV− cohort was not reported. Because of sparse data the quality of evidence supporting this outcome is very low indicating death censored graft survival is uncertain.
Both the CD4+ T-cell count and HIV viral load appear controlled post transplant with an incidence of opportunistic infection of 20.5%. However, the quality of this evidence for these outcomes is very low indicating uncertainty in these effects. Similarly, because of very low quality evidence there is uncertainty in the rate of acute graft rejection among both the HIV+ and HIV− groups
Liver Transplantation: HIV+/HCV+ vs. HCV+
Based on a combined HIV+/HCV+ cohort sample size of 156 from seven studies, the risk of death after liver transplantation is significantly greater (2.8 fold) in a co-infected cohort compared with an HCV+ mono-infected cohort (HR: 2.81; 95% CI: 1.47, 5.37). The quality of evidence supporting this outcome is very low. Death censored graft survival evidence was not available.
Regarding disease progression, based on a combined sample size of 71 persons in the co-infected cohort, the CD4+ T-cell count and HIV viral load appear controlled post transplant; however, again the quality of evidence supporting this outcome is very low. The rate of opportunistic infection in the co-infected cohort was 7.2%. The quality of evidence supporting this estimate is very low, indicating uncertainty in these estimates of effect.
Based on a combined HIV+/HCV+ cohort (n=57) the rate of acute graft rejection does not differ to that of an HCV+ mono-infected cohort (OR: 0.88; 95% CI: 0.44, 1.76). Also based on a combined HIV+/HCV+ cohort (n=83), the rate of HCV+ recurrence does not differ to that of an HCV+ mono-infected cohort (OR: 0.66; 95% CI: 0.27, 1.59). In both cases, the quality of the supporting evidence was very low.
Overall, because of very low quality evidence there is uncertainty in the effect of kidney or liver transplantation in HIV+ persons with end stage organ failure compared with those not infected with HIV. Examining the economics of this issue, the cost of kidney and liver transplants in an HIV+ patient population are, on average, 56K and 147K per case, based on both Canadian and American experiences.
PMCID: PMC3377507  PMID: 23074407
9.  Impact of Antiretroviral Therapy on the Incidence of Tuberculosis: The Brazilian Experience, 1995–2001 
PLoS ONE  2007;2(9):e826.
Background
The human immunodeficiency virus (HIV) fuels tuberculosis (TB) epidemics. In controlled clinical trials, antiretroviral therapy (ART) reduces TB incidence in HIV-infected patients. In this study we determine if, under programmatic conditions, Brazil's policy of universal ART access has impacted TB incidence among HIV-infected patients.
Methods
We abstracted clinical information from records of HIV-infected patients managed in the public sector in 11 Brazilian states between 1/1/1995 and 12/31/2001. Case ascertainment (TB and HIV) utilized guidelines (with added stringency) published by Brazil's Ministry of Health. We determined TB incidence and hazards ratio (HR) for ART-naïve and ART-treated [including highly active ART (HAART)] patients employing Cox proportional hazards analysis.
Results
Information from 463 HIV-infected patients met study criteria. The median age of the study population was 34 years, 70% were male, and mean follow-up to primary endpoints—TB, death, and last clinic visit—was 330, 1059, and 1125 days, respectively. Of the 463 patients, 76 (16%) remained ART-naïve. Of the patients who never received HAART (n = 157) 81 were treated with ART non-HAART. Of the patients who received any ART (n = 387), 306 were treated with HAART (includes those patients who later switched from ART non-HAART to HAART). Tuberculosis developed in 39/463 (8%) patients. Compared to HAART- and ART non-HAART-treated patient groups, TB incidence was 10- (p<0.001) and 2.5-fold (p = 0.03) higher in ART-naïve patients, respectively. The median baseline absolute CD4+ T-lymphocyte count for patients who developed TB was not significantly different from that of patients who remained TB free. In multivariate analysis, the incidence of TB was statistically significantly lower in HAART-treated [HR 0.2; 95% (CI 0.1, 0.6); p<0.01] compared to ART naïve patients. A baseline CD4+ T-lymphocyte count <200 cells/mm3 [HR 2.5; (95% CI 1.2, 5.4); p<0.01], prior hospitalization [HR 4.2; (95% CI 2.0, 8.8); p<0.001], prior incarceration [HR 4.1; 95% CI 1.6, 10.3); p<0.01], and a positive tuberculin skin test [HR 3.1; (95% CI 1.1, 9.0); p = 0.04] were independently and positively associated with incident TB.
Conclusion
In this population-based study we demonstrate an 80% reduction in incident TB, under programmatic conditions, in HAART-treated HIV-infected patients compared to ART-naïve patients.
doi:10.1371/journal.pone.0000826
PMCID: PMC1952142  PMID: 17786198
10.  Immune reconstitution inflammatory syndrome among HIV-infected South African infants initiating antiretroviral therapy 
AIDS (London, England)  2009;23(9):1097-1107.
Objectives
To determine the incidence, clinical manifestations and risk factors for immune reconstitution inflammatory syndrome (IRIS) in young children initiating highly active antiretroviral therapy (HAART).
Design
A prospective cohort of antiretroviral-naïve HIV-infected children less than 24 months of age enrolled in a treatment strategies trial in Johannesburg, South Africa.
Methods
Among 169 HIV-infected children initiating HAART, April 2005 to November 2006, the records of 83 children suspected to have IRIS within 6 months of starting treatment were reviewed to determine whether they met criteria for IRIS. Seven were excluded due to incomplete follow-up. Pretreatment and post-treatment characteristics of children with and without IRIS were compared.
Results
Overall, 34/162 (21%) children developed IRIS at a median of 16 days (range 7–115 days) post-HAART initiation. Bacille Calmette-Guérin reaction was most common occurring in 24/34 (71%) children, primarily injection site lesions and/or ipsilateral axillary lymphadenitis with abscess. Other IRIS conditions (not mutually exclusive) included Mycobacterium tuberculosis (n = 12), cytomegalovirus pneumonia (n = 1), Streptococcus pneumonia sepsis (n = 1), and severe seborrheic dermatitis (n = 1). Children with IRIS were younger (median age 7 vs. 10 months, P = 0.007) with a lower CD4 cell percentage (median 13.9 vs. 19.2, P = 0.009) at HAART initiation than controls. After 24 weeks on HAART, 62% of IRIS cases vs. 28% of controls had HIV RNA more than 400 copies/ml (P = 0.001), odds ratio = 2.88 (95% confidence interval = 1.14–7.29) after adjusting for baseline factors.
Conclusion
Infants and young children with advanced HIV disease initiating HAART are at high risk for developing IRIS, leading to additional morbidity and possibly impairing virologic response to antiretroviral treatment.
doi:10.1097/QAD.0b013e32832afefc
PMCID: PMC2810152  PMID: 19417581
immune reconstitution inflammatory syndrome; pediatric HAART; pediatric HIV
11.  Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting 
Background
Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression.
Methods
The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity.
Results
Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels.
Conclusions
Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy.
doi:10.1086/587900
PMCID: PMC3154876  PMID: 18426371
12.  Prevalence of Anemia and Immunological Markers in HIV-Infected Patients on Highly Active Antiretroviral Therapy in Northeastern Nigeria 
Infectious Diseases  2013;6:25-33.
Background
There are conflicting reports on the impact of highly active antiretroviral therapy (HAART) in resolving hematological complications. Whereas some studies have reported improvements in hemoglobin and other hematological parameters resulting in reduction in morbidity and mortality of HIV patients, others have reported no improvement in hematocrit values of HAART-treated HIV patients compared with HAART-naïve patients.
Objective
This current study was designed to assess the impact of HAART in resolving immunological and hematological complications in HIV patients by comparatively analyzing the results (immunological and hematological) of HAART-naive patients and those on HAART in our environment.
Methods
A total of 500 patients participated, consisting of 315 HAART-naive (119 males and 196 females) patients and 185 HAART-experienced (67 males and 118 females) patients. Hemoglobin (Hb), CD4+ T-cell count, total white blood count (WBC), lymphocyte percentage, plateletes, and plasma HIV RNA were determined.
Results
HAART-experienced patients were older than their HAART-naive counterparts. In HAART-naive patients, the incidence of anemia (packed cell volume [PCV] <30%) was 57.5%, leukopenia (WBC < 2.5), 6.1%, and thrombocytopenia < 150, 9.6%; it was, significantly higher compared with their counterparts on HAART (24.3%, 1.7%, and 1.2%, respectively). The use of HAART was not associated with severe anemia. Of HAART-naive patients, 57.5% had a CD4 count < 200 cells/μL in comparison with 20.4% of HAART-experienced patients (P < 0.001). The mean viral load log10 was significantly higher in HAART-naive than in HAART-experienced patients (P < 0.001). Total lymphocyte count < 1.0 was a significant predictor of
Conclusion
HAART has the capability of reducing the incidence of anemia, other deranged hematological and immunological parameters associated with disease progression, and death in HIV-infected patients. Total lymphocyte count fails to predict CD4 count < 200 cells/μL in our cohort; thus, its use in the management and monitoring of HIV-infected patients in our settings is not reliable.
doi:10.4137/IDRT.S10477
PMCID: PMC3988622  PMID: 24847174
antiretroviral; lymphocyte; total leukocyte count; CD4; World Health Organization/Aids Clinical Trials Group
PLoS ONE  2015;10(2):e0117715.
Background
Intestinal parasites (IPs) are major concerns in most developing countries where HIV/AIDS cases are concentrated and almost 80% of AIDS patients die of AIDS-related infections. In the absence of highly active antiretroviral therapy (HAART), HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic and other intestinal parasites. The aim of the study was to determine the prevalence of intestinal parasites in relation to CD4+ T cells levels and anemia among HAART initiated and HAART naïve pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia.
Methods
A prospective comparative cross-sectional study was conducted among HAART initiated and HAART naive pediatric HIV/AIDS patients attending a model ART center at Zewditu Memorial Hospital between August 05, 2013 and November 25, 2013. A total of 180 (79 HAART initiated and 101 HAART naïve) children were included by using consecutive sampling. Stool specimen was collected and processed using direct wet mount, formol-ether concentration and modified Ziehl-Neelsen staining techniques. A structured questionnaire was used to collect data on socio-demographic and associated risk factors. CD4+ T cells and complete blood counts were performed using BD FACScalibur and Cell-Dyn 1800, respectively. The data was analyzed by SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. P values < 0.05 were taken as statistically significant.
Results
The overall prevalence of IPs was 37.8% where 27.8% of HAART initiated and 45.5% of HAART naive pediatric HIV/AIDS patients were infected (p < 0.05). Cryptosporidium species, E. histolytica/dispar, Hook worm and Taenia species were IPs associated with CD4+ T cell counts <350 cells/μμL in HAART naive patients. The overall prevalence of anemia was 10% in HAART and 31.7% in non-HAART groups. Hook worm, S. stercoralis and H. nana were helminthes significantly associated with anemia in non-HAART patients [AOR, 95% CI: 4.5(1.3, 15.2), P< 0.05]. The prevalence of IPs in non-HAART patients was significantly associated with eating unwashed/raw fruit [AOR, 95%CI: 6.3(1.2, 25.6), P<0.05], open field defecation [AOR, 95%CI: 9.3(1.6, 53.6), P<0.05] and diarrhea [AOR, 95%CI: 5.2(1.3, 21.3), P<0.05]. IPs significantly increased in rural residents [AOR, 95%CI: 0.4(0.1, 0.9, P<0.05)].
Conclusion
The overall prevalence of intestinal parasites significantly differed by HAART status and cryptosporidium species were found only in HAART naïve patients with low CD4+ T cell counts. Anemia was also more prevalent and significantly associated with IPs in non-HAART patients. This study identified some environmental and associated risk factors for intestinal parasitic infections. Therefore, Public health measures should continue to emphasize the importance of environmental and personal hygiene to protect HIV/AIDS patients from infections with intestinal parasites and maximize the benefits of HAART.
doi:10.1371/journal.pone.0117715
PMCID: PMC4320101  PMID: 25658626
Context
Highly active antiretroviral treatment (HAART) usage in India is escalating. With the government of India launching the free HAART rollout as part of the "3 by 5" initiative, many people living with HIV/AIDS (PLHA) have been able to gain access to HAART medications. Currently, the national HAART centers are located in a few district hospitals (in the high- and medium-prevalence states) and have very stringent criteria for enrolling PLHA. Patients who do not fit these criteria or patients who are too ill to undergo the prolonged wait at the government hospitals avail themselves of nongovernment organization (NGO) services in order to take HAART medications. In addition, the government program has not yet started providing second-line HAART (protease inhibitors). Hence, even with the free HAART rollout, NGOs with the expertise to provide HAART continue to look for funding opportunities and other innovative ways of making HAART available to PLHA. Currently, no study from Indian NGOs has compared the direct and indirect costs of solely managing opportunistic infections (OIs) vs HAART.
Objective
Compare direct medical costs (DMC) and nonmedical costs (NMC) with 2005 values accrued by the NGO and PLHA, respectively, for either HAART or exclusive OI management.
Study design
Retrospective case study comparison.
Setting
Low-cost community care and support center - Freedom Foundation (NGO, Bangalore, south India).
Patients
Retrospective analysis data on PLHA accessing treatment at Freedom Foundation between January 1, 2003 and January 1, 2005. The HAART arm included case records of PLHA who initiated HAART at the center, had frequent follow-up, and were between 18 and 55 years of age. The OI arm included records of PLHA who were also frequently followed up, who were in the same age range, who had CD4+ cell counts < 200/microliter (mcL) or an AIDS-defining illness, and who were not on HAART (solely for socioeconomic reasons). A total of 50 records were analyzed. Expenditures on medication, hospitalization, diagnostics, and NMC (such as food and travel for a caregiver) were calculated for each group.
Results
At 2005 costs, the median DMC plus NMC in the OI group was 21,335 Indian rupees (Rs) (mean Rs 24,277/-) per patient per year (pppy) (US $474). In the HAART group, the median DMC plus NMC was Rs 18,976/- (mean Rs 21,416/-) pppy (US $421). Median DMC plus NMC pppy in the OI arm was Rs 13623.7/- paid by NGO and Rs 1155/- paid by PLHA. Median DMC and NMC pppy in the HAART arm were Rs 1425/- paid by NGO and Rs 17,606/- paid by PLHA.
Conclusion
Good health at no increased expenditure justifies providing PLHA with HAART even in NGO settings.
doi:10.1186/1758-2652-8-4-24
PMCID: PMC2765856
Background
Little is known about immune-reconstitution inflammatory syndrome (IRIS) in children in the United States.
Methods
LEGACY is a longitudinal cohort study of HIV-infected participants age 0-24 years at enrollment during 2005-2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the six months pre- and post-initiation of the first HAART regimen with a virologic response. We defined OI as IRIS if an OI’s incidence increased after HAART initiation. “Responders” were defined as experiencing ≥1 log decline in viral load within six months following HAART initiation.
Results
Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were non-responders, and 86 experienced OI. Responders accounted for 98/124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders, and 15.9 and 9.1 (P =0.2), respectively, among non-responders. Overall, OI incidences among responders and non-responders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely to experience herpes simplex, herpes zoster, and CMV, before HAART initiation (all, P<0.05).
Conclusions
We detected few OIs and no IRIS among participants initiating HAART. The unexpectedly higher OI prevalence among responders, mostly occurring before HAART initiation, may have motivated higher adherence by responders and subsequent categorization as a responder.
doi:10.1097/INF.0b013e31829ee893
PMCID: PMC3785006  PMID: 24067552
HIV infection; pediatric; immune reconstitution inflammatory syndrome (IRIS); opportunistic infection; highly active antiretroviral therapy
Background
African Americans with human immunodeficiency virus type 1 (HIV-1) infection and kidney disease are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT), particularly in urban areas with high rates of poverty and injection drug use. It is unknown how the widespread use of highly active antiretroviral therapy (HAART) has affected survival during RRT in this vulnerable population.
Methods
African American patients infected with HIV-1 who required RRT were identified from 2 cohorts that included 4509 Africans Americans infected with HIV-1 who were recruited during the period 1988–2004 in Baltimore, Maryland. Survival after initiation of RRT was compared for those who initiated treatment in the pre-HAART and the HAART eras using Kaplan-Meier curves. Cox proportional hazards regression analysis was used to adjust for potential confounders.
Results
RRT was initiated in 162 patients (3.6%) during 10.6 years of follow-up (119 during the HAART era). Compared with patients who started RRT in the pre-HAART era, those in the HAART era were older (P< .001) and more likely to have CD4 cell counts of ≥200 cells/mm3 (P = .01). A total of 126 patients (78%) died during follow-up; among those who initiated RRT during the HAART era, 87 deaths occurred (73%). Median survival time in the pre-HAART era was 22.4 months (95% confidence interval [CI], 9.3–30.7); during the HAART era, it was 19.9 months (95% CI, 14.7–26.5; P = .94). In the multiple Cox regression model, factors independently associated with increased mortality included age (hazard ratio [HR], 1.30; 95% CI, 1.06–1.60; P = .01), lower serum albumin level (HR, 0.72; 95% CI, 0.57–0.91; P< .007), lower CD4 cell count (HR, 0.90; 95% CI, 0.82–0.99; P< .03), and the lack of HAART (HR, 0.52; 95% CI, 0.33–0.82; P = .005).
Conclusions
Older age, lower serum albumin level, lower CD4 cell count, and the lack of HAART are independent predictors of poor survival among African Americans infected with HIV-1 undergoing RRT in a resource-limited urban area. RRT survival was similar in the pre-HAART and HAART eras, likely reflecting inadequate HIV treatment in this population.
doi:10.1086/523728
PMCID: PMC4096866  PMID: 18190325
JAMA pediatrics  2013;167(6):520-527.
Objective
To determine the cardiac effects of prolonged exposure to highly active antiretroviral therapy (HAART) on HIV-infected (HIV+) children.
Design
In the National Institutes of Health (NIH)-funded Pediatric HIV/AIDS Cohort Study’s Adolescent Master Protocol (AMP), we used linear regression models to compare echocardiogram measures.
Setting
14 U.S. pediatric HIV clinics.
Patients/Participants
Perinatally-infected HIV+ children receiving HAART with HIV-exposed but uninfected (HEU) children and HIV+ (mostly HAART-unexposed) historical pediatric controls from the NIH-funded Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection (P2C2-HIV) Study.
Main Exposure
Long-term HAART.
Outcome Measures
Echocardiographic measures of left ventricular (LV) function and structure.
Results
The 325 AMP HIV+ children had lower viral loads, higher CD4 counts, and longer duration of antiretroviral therapy than 70 P2C2 HIV+ children (all P’s < 0·001). Z scores for LV fractional shortening (a measure of cardiac function) were significantly lower among P2C2 HIV+ children than among the AMP HIV+ group or the 189 AMP HEU controls (P < 0.05). For HIV+ children, lower nadir CD4 percentage and higher current viral load were associated with significantly lower cardiac function (LV contractility and LV fractional shortening Z scores; P’s = 0.001) and increased LV end-systolic dimension Z score (P’s < 0.03). In an interaction analysis by HIV+ cohort, P2C2 HIV+ children with longer ART exposure or lower nadir CD4 percentage had lower mean LV fractional shortening Z scores, while mean Z scores were relatively constant among AMP HIV+ children (P<0·05 for all interactions).
Conclusions
HAART appears to be cardioprotective in HIV+ children and adolescents.
doi:10.1001/jamapediatrics.2013.1206
PMCID: PMC4180681  PMID: 23608879
PLoS ONE  2011;6(12):e27907.
Objectives
We describe pregnant womens' access to PMTCT and HAART services and associated birth outcomes in South Africa.
Methods
Women recuperating in postnatal wards of a referral hospital participated in an evaluation during February–May 2010 during which their maternity records were examined to describe their access to VCT, CD4 Counts, dual ART or HAART during pregnancy.
Results
Of the 1609 women who participated in this evaluation, 39% (95%CI36.7–41.5%) tested HIV-positive during their pregnancy. Of the HIV-positive women 2.9% did not have a CD4 count done and an additional 31.3% did not receive their CD4 results. The majority (96.8%) of the HIV-positive women commenced dual ART at their first antenatal visit independent of their CD4 result. During February–May 2010, 48.0% of the women who had a CD4 result were eligible for HAART (CD4<200 cells/mm3) and 29.1% of these initiated HAART during pregnancy. Under the current South African PMTCT guidelines 71.1% (95%CI66.4–75.4%) of HIV positive pregnant women could be eligible for HAART (CD4<350 cells/mm3). There were significantly more preterm births among HIV-positive women (p = 0.01) and women who received HAART were no more at risk of preterm deliveries (AOR 0.73;95%CI0.39–1.36;p = 0.2) as compared to women who received dual ART. Nine (2.4%; 95%CI1.1–4.5%) HIV exposed infants were confirmed HIV infected at birth. The in-utero transmission rate was highest among women who required HAART but did not initiate treatment (8.5%) compared to 2.7% and 0.4% among women who received HAART and women who were not eligible for HAART and received PMTCT prophylaxis respectively.
Conclusion
In this urban South African community the antenatal HIV prevalence remains high (39%) and timeous access to CD4 results during pregnancy is limited. Under the current South African guidelines, and assuming that access to CD4 results has improved, more than 70% of HIV-positive pregnant women in this community would be requiring HAART.
doi:10.1371/journal.pone.0027907
PMCID: PMC3230616  PMID: 22162993
Background
As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression.
Methods
With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables.
Results
We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782–29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P<0.001) and inversely correlated with current CD4 T-cell count (P=0.024). Site of care held independent prediction of higher costs, with marked control of expenses at sites 2 (P=0.001) and 5 (P<0.001).
Conclusion
Higher costs of HAART were strongly associated with previous treatment failures, detectable HIV viremia, and lower CD4 T-cell count at the time of evaluation, with no correlation at all with sex, age, hepatitis C virus coinfection, and nadir CD4 T-cell counts. Newer drugs, which are typically those associated with high prices, at the time of the analysis were still prevalently prescribed to rescue and maintain viral suppression in patients with more complex treatment history. Further analyses of the contribution of the single drug/regimen to the estimated cost are warranted.
doi:10.2147/CEOR.S69183
PMCID: PMC4278727  PMID: 25565872
highly active antiretroviral treatment; human immunodeficiency virus; costs; treatment failures; viremia; current CD4 count
Background:
The aims of this study were to determine the pattern and frequency of oral lesions and to compare the prevalence of HIV-related oral lesions in paediatric Nigerian patients on HAART with those not on HAART.
Materials and Methods:
All patients aged 15 years and below attending the Infectious Disease Clinic of Aminu Kano Teaching Hospital with a diagnosis of HIV were consecutively examined in a cross-sectional study over a 2-year period. Information was obtained by history, physical examinations, HIV testing, and enumeration of CD+ T cells. The results are presented. A P-value of <0.05 was considered significant.
Results:
A total of 105 children comprising 63 males and 42 female who met the inclusion criteria participated in the study, mean age in months was 53.3±42.2, with a mean of 3.4±2.2 for male and 2.8±1.8 for female respectively. Oral lesions occurred in 61.9% of the children Overall, 22 (21.0%) had at least one oral lesion, 43 (41.0%) had multiple lesion. The most common lesion was oral candidiasis (79.1%). The angular cheilitis (43.8%) variant was most frequent. The mean CD4 counts were 1138 cells/mm3, 913 cells/mm3 and 629 cells/mm3 for those without oral lesion, with single lesion and multiple oral lesions respectively. These differences were not statistically significant (ANOVA: F=0.185, df=2, 80, 82, P=0.831. Patients on HAART comprised about 61.9% and these were found to have reduced risk for development of such oral lesions as angular cheilitis (OR=0.76; 95% CI=0.56-1.02; P=0.03), pseudomembranous candidiasis (OR=0.71; 95% CI=0.54-0.94; P=0.024) and HIV-gingivitis (OR=0.59; 95% CI=0.46-0.75; P=0.001). HAART had some beneficial but insignificant effect on development of HIV-periodonttitis (OR=0.60; 95% CI=0.51-0.70; P=0.09). The chances of occurrence of other oral lesions were not significantly reduced by HAART (Kaposi sarcoma, OR=1.24; 95% CI=0.31-5.01; P=0.47, erythematous candidiasis, OR=1.13; 95% CI=0.62-2.06).
Conclusion:
HIV-related Oral lesions are frequently seen in HIV-infected Nigerian children. Paediatric patients receiving HAART had significantly lower prevalence of oral lesions, particularly oral candidiasis and HIV-gingivitis.
doi:10.4103/0300-1652.104385
PMCID: PMC3531035  PMID: 23293416
HIV/AIDS; Nigeria; oral manifestations; paediatrics
BMC Oral Health  2006;6:12.
Background
The aim of the study was to compare the prevalence and types of HIV-related oral lesions between children and adult Tanzanian patients on HAART with those not on HAART and to relate the occurrence of the lesions with anti-HIV drug regimen, clinical stage of HIV disease and CD4+ cell count.
Methods
Participants were 532 HIV infected patients, 51 children and 481 adults, 165 males and 367 females. Children were aged 2–17 years and adults 18 and 67 years. Participants were recruited consecutively at the Muhimbili National Hospital (MNH) HIV clinic from October 2004 to September 2005. Investigations included; interviews, physical examinations, HIV testing and enumeration of CD4+ T cells.
Results
A total of 237 HIV-associated oral lesions were observed in 210 (39.5%) patients. Oral candidiasis was the commonest (23.5%), followed by mucosal hyperpigmentation (4.7%). There was a significant difference in the occurrence of oral candidiasis (χ2 = 4.31; df = 1; p = 0.03) and parotid enlargement (χ2 = 36.5; df = 1; p = 0.04) between children and adults. Adult patients who were on HAART had a significantly lower risk of; oral lesions (OR = 0.32; 95% CI = 0.22 – 0.47; p = 0.005), oral candidiasis (OR = 0.28; 95% CI = 0.18 – 0.44; p = 0.003) and oral hairy leukoplakia (OR = 0.18; 95% CI = 0.04 – 0.85; p = 0.03). There was no significant reduction in occurrence of oral lesions in children on HAART (OR = 0.35; 95% CI = 0.11–1.14; p = 0.15). There was also a significant association between the presence of oral lesions and CD4+ cell count < 200 cell/mm3 (χ2 = 52.4; df = 2; p = 0.006) and with WHO clinical stage (χ2 = 121; df = 3; p = 0.008). Oral lesions were also associated with tobacco smoking (χ2 = 8.17; df = 2; p = 0.04).
Conclusion
Adult patients receiving HAART had a significantly lower prevalence of oral lesions, particularly oral candidiasis and oral hairy leukoplakia. There was no significant change in occurrence of oral lesions in children receiving HAART. The occurrence of oral lesions, in both HAART and non-HAART patients, correlated with WHO clinical staging and CD4+ less than 200 cells/mm3.
doi:10.1186/1472-6831-6-12
PMCID: PMC1559688  PMID: 16916469
Background
Although highly active antiretroviral therapy (HAART) reduces mortality in the developed world, it remains undocumented in resource-poor settings. We assessed the effect of HAART on patient mortality and tuberculosis incidence rate under routine clinical care conditions in Ethiopia. The objective of this study was to assess the effect of HAART on patient mortality and tuberculosis incidence rate under routine clinical care conditions in a resource-limited setting in south Ethiopia. Starting in January 2003, we followed all consecutive adult HIV infected patients who visited the HIV clinic. Since August 2003, we treated patients with HAART. Only basic laboratory services were available.
Results
We followed 185 patients in the pre-HAART cohort and 180 patients in the HAART cohort. The mortality rate was 15.4 per 100 person-years of observation (PYO) in the HAART group and tuberculosis incidence rate was 3.7 per 100 PYO. In the pre-HAART group, the mortality rate was 58.1 per 100 PYO and the tuberculosis incidence rate was 11.1 per 100 PYO. HAART resulted in a 65% decline in mortality (adjusted hazard ratio [95%CI] = 0.35 [0.19–0.63]; P < 0.001). Tuberculosis incidence rate was lower in the HAART group (adjusted hazard ratio [95%CI] = 0.11 [0.03–0.48]; P < 0.01). Most of the deaths occurred during the first three months of treatment.
Conclusion
HAART improved survival and decreased tuberculosis incidence to a level similar to that achieved in the developed countries during the early years of HAART. However, both the mortality and the tuberculosis incidence rate were much higher in terms of absolute figures in this resource-limited setting. Attention should be paid to the early weeks of treatment when mortality is high. The high tuberculosis incidence rate, when coupled with the improved survival, may lead to increased tuberculosis transmission. This highlights the need for strengthening tuberculosis prevention efforts with the scale-up of treatment programmes
doi:10.1186/1742-6405-3-10
PMCID: PMC1475602  PMID: 16600050
BMC Infectious Diseases  2014;14:304.
Background
Optimal timing for initiating highly active antiretroviral therapy (HAART) in HIV-TB coinfected patients is challenging for clinicians. We aim to evaluate the impact of different timing of HAART initiation on TB outcome of HIV-infected adults in Taiwan.
Methods
A population-based retrospective cohort study was conducted through linking the HIV and TB registries of Taiwan Centers for Disease Control (CDC) during 1997 to 2006. Clinical data of HIV-TB co-infected patients, including the presence of immune reconstitution inflammatory syndrome (IRIS), was collected through medical records review. The outcome of interest was all-cause mortality within 1 year following TB diagnosis. The Cox proportional hazard model was used to explore the probability of death and IRIS after TB diagnosis by adjusting for confounding factors and factors of interest. The probability of survival and TB IRIS were calculated by the Kaplan-Meier method and compared between different HAART initiation timing groups by the log-rank test.
Results
There were 229 HIV-TB co-infected patients included for analysis and 60 cases (26.2%) died within one year. Besides decreasing age and increasing CD4 lymphocyte count, having started HAART during TB treatment was significantly associated with better survival (adjusted Hazard Ratio was 0.11, 95% CI 0.06–0.21). As to the timing of HAART initiation, there was only non-significant benefit on survival among cases initiating HAART within 15 days, at 16–30 days and at 31–60 days of TB treatment than initiating after 60 days. Cases with HAART initiated after 30 days had lower risk in developing IRIS than cases with HAART initiated earlier. Cases with IRIS had significantly higher rate of re-hospitalization (49% vs. 4%, p < 0.001) and prolonged hospitalization (28 days vs. 18.5 days, p < 0.01).
Conclusion
The present study found that starting HAART during TB treatment is associated with better one-year survival, although earlier initiation within 60 days of TB treatment did not show statistical differences in survival than later initiation. Initiation of HAART within 30 days appeared to increase the risk of IRIS. Deferring HAART to 31–60 days of TB treatment might be optimal after considering the risks and benefits.
doi:10.1186/1471-2334-14-304
PMCID: PMC4058447  PMID: 24897928
Tuberculosis; HIV; Mortality; HAART
PLoS Medicine  2013;10(8):e1001494.
Using a randomized controlled trial, Marc Lallemant and colleagues ask if a CD4-based monitoring and treatment switching strategy provides a similar clinical outcome compared to the standard viral load-based strategy for adults with HIV in Thailand.
Please see later in the article for the Editors' Summary
Background
Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.
Methods and Findings
The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50–250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6–11.4) in VL versus 7.4% (5.1–10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2–8.4) in VL versus 7.5% (5.0–11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7–19.4) in VL and 24.7 months (15.9–35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8–8.0) in VL versus 15.8 months (8.5–20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.
Conclusions
The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.
Trial registration
ClinicalTrials.gov NCT00162682
Please see later in the article for the Editors' Summary
Editors' Summary
Background
About 34 million people (most of them living in low-and middle-income countries) are currently infected with HIV, the virus that causes AIDS. HIV infection leads to the destruction of immune system cells (including CD4 cells, a type of white blood cell), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected individuals died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (HAART)—combined drugs regimens that suppress viral replication and allow restoration of the immune system—became available. For people living in affluent countries, HIV/AIDS became a chronic condition but, because HAART was expensive, HIV/AIDS remained a fatal illness for people living in resource-limited countries. In 2003, the international community declared HIV/AIDS a global health emergency and, in 2006, it set the target of achieving universal global access to HAART by 2010. By the end of 2011, 8 million of the estimated 14.8 million people in need of HAART in low- and middle-income countries were receiving treatment.
Why Was This Study Done?
At the time this trial was conceived, national and international recommendations were that HIV-positive individuals should start HAART when their CD4 count fell below 200 cells/mm3 and should have their CD4 count regularly monitored to optimize HAART. In 2013, the World Health Organization (WHO) recommendations were updated to promote expanded eligibility for HAART with a CD4 of 500 cells/mm3 or less for adults, adolescents, and older children although priority is given to individuals with CD4 count of 350 cells/mm3 or less. Because HIV often becomes resistant to first-line antiretroviral drugs, WHO also recommends that viral load—the amount of virus in the blood—should be monitored so that suspected treatment failures can be confirmed and patients switched to second-line drugs in a timely manner. This monitoring and switching strategy is widely used in resource-rich settings, but is still very difficult to implement for low- and middle-income countries where resources for monitoring are limited and access to costly second-line drugs is restricted. In this randomized non-inferiority trial, the researchers compare the performance of a CD4-based treatment monitoring and switching strategy with the standard viral load-based strategy among HIV-positive adults in Thailand. In a randomized trial, individuals are assigned different interventions by the play of chance and followed up to compare the effects of these interventions; a non-inferiority trial investigates whether one treatment is not worse than another.
What Did the Researchers Do and Find?
The researchers assigned about 700 HIV-positive adults who were beginning HAART for the first time to have their CD4 count (CD4 arm) or their CD4 count and viral load (VL arm) determined every 3 months. Participants were switched to a second-line therapy if their CD4 count declined by more than 30% from their peak CD4 count (CD4 arm) or if a viral load of more than 400 copies/ml was recorded (VL arm). The 3-year cumulative risk of clinical failure (defined as death, a new AIDS-defining event, or a CD4 count of less than 50 cells/mm3) was 8% in the VL arm and 7.4% in the CD4 arm. This difference in clinical failure risk met the researchers' predefined criterion for non-inferiority. The probability of a treatment switch was similar in the two arms, but the average time from treatment initiation to treatment switch and the average duration of a high viral load after treatment switch were both longer in the CD4 arm than in the VL arm. Finally, the future-drug-option score, a measure of viral drug resistance profiles, was similar in the two arms at the time of treatment switch.
What Do These Findings Mean?
These findings suggest that, in Thailand, a CD4 switching strategy is non-inferior in terms of clinical outcomes among HIV-positive adults 3 years after beginning HAART when compared to the recommended viral load-based switching strategy and that there is no difference between the strategies in terms of viral suppression and immune restoration after 3-years follow-up. Importantly, however, even though patients in the CD4 arm spent longer with a high viral load than patients in the VL arm, the emergence of HIV mutants resistant to antiretroviral drugs was similar in the two arms. Although these findings provide no information about the long-term outcomes of the two monitoring strategies and may not be generalizable to routine care settings, they nevertheless provide reassurance that using CD4 counts alone to monitor HAART in HIV treatment programs in resource-limited settings is an appropriate strategy to use as viral load measurement becomes more affordable and feasible in these settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001494.
The World Health Organization provides information on all aspects of HIV/AIDS (in several languages); its 2010 recommendations for antiretroviral therapy for HIV infection in adults and adolescents are available as well as the June 2013 Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach
The 2012 UNAIDS World AIDS Day Report provides up-to-date information about the AIDS epidemic and efforts to halt it
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the global HIV/AIDS epidemic, on HIV and AIDS in Thailand, on universal access to AIDS treatment, and on starting, monitoring and switching HIV treatment (in English and Spanish)
The UK National Health Service Choices website provides information (including personal stories) about HIV and AIDS
More information about this trial (the PHPT-3 trial) is available
Patient stories about living with HIV/AIDS are available through Avert; the nonprofit website Healthtalkonline also provides personal stories about living with HIV, including stories about HIV treatment
doi:10.1371/journal.pmed.1001494
PMCID: PMC3735458  PMID: 23940461
PLoS ONE  2010;5(11):e13868.
Objective
Preventing unintended pregnancy among HIV-positive women constitutes a critical and cost-effective approach to primary prevention of mother-to-child transmission of HIV and is a global public health priority for addressing the desperate state of maternal and child health in HIV hyper-endemic settings. We sought to investigate whether the prevalence of contraceptive use and method preferences varied by HIV status and receipt of highly active antiretroviral therapy (HAART) among women in Soweto, South Africa.
Methods
We used survey data from 563 sexually active, non-pregnant women (18–44 years) recruited from the Perinatal HIV Research Unit in Soweto (May–December, 2007); 171 women were HIV-positive and receiving HAART (median duration of use = 31 months; IQR = 28, 33), 178 were HIV-positive and HAART-naïve, and 214 were HIV-negative. Medical record review was conducted to confirm HIV status and clinical variables. Logistic regression models estimated adjusted associations between HIV status, receipt of HAART, and contraceptive use.
Results
Overall, 78% of women reported using contraception, with significant variation by HIV status: 86% of HAART users, 82% of HAART-naïve women, and 69% of HIV-negative women (p<0.0001). In adjusted models, compared with HIV-negative women, women receiving HAART were significantly more likely to use contraception while HAART-naïve women were non-significantly more likely (AOR: 2.40; 95% CI: 1.25, 4.62 and AOR: 1.59; 95% CI: 0.88, 2.85; respectively). Among HIV-positive women, HAART users were non-significantly more likely to use contraception compared with HAART-naïve women (AOR: 1.55; 95% CI: 0.84, 2.88). Similar patterns held for specific use of barrier (primarily male condoms), permanent, and dual protection contraceptive methods.
Conclusion
Among HIV-positive women receiving HAART, the observed higher prevalence of contraceptive use overall and condoms in particular promises to yield fewer unintended pregnancies and reduced risks of vertical and sexual HIV transmission. These findings highlight the potential of integrated HIV and reproductive health services to positively impact maternal, partner, and child health.
doi:10.1371/journal.pone.0013868
PMCID: PMC2974641  PMID: 21079770

Results 1-25 (1143298)