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Population-Based CD4 Counts in a Rural Area in South Africa with High HIV Prevalence and High Antiretroviral Treatment Coverage  [PDF]
Abraham Malaza, Jo?l Mossong, Till B?rnighausen, Johannes Viljoen, Marie-Louise Newell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070126
Abstract: Background Little is known about the variability of CD4 counts in the general population of sub-Saharan Africa countries affected by the HIV epidemic. We investigated factors associated with CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment (ART) coverage. Methods CD4 counts, health status, body mass index (BMI), demographic characteristics and HIV status were assessed in 4990 adult resident participants of a demographic surveillance in rural KwaZulu-Natal in South Africa; antiretroviral treatment duration was obtained from a linked clinical database. Multivariable regression analysis, overall and stratified by HIV status, was performed with CD4 count levels as outcome. Results Median CD4 counts were significantly higher in women than in men overall (714 vs. 630 cells/μl, p<0.0001), both in HIV-uninfected (833 vs. 683 cells/μl, p<0.0001) and HIV-infected adults (384.5 vs. 333 cells/μl, p<0.0001). In multivariable regression analysis, women had 19.4% (95% confidence interval (CI) 16.1–22.9) higher CD4 counts than men, controlling for age, HIV status, urban/rural residence, household wealth, education, BMI, self-reported tuberculosis, high blood pressure, other chronic illnesses and sample processing delay. At ART initiation, HIV-infected adults had 21.7% (95% CI 14.6–28.2) lower CD4 counts than treatment-naive individuals; CD4 counts were estimated to increase by 9.2% (95% CI 6.2–12.4) per year of treatment. Conclusions CD4 counts are primarily determined by sex in HIV-uninfected adults, and by sex, age and duration of antiretroviral treatment in HIV-infected adults. Lower CD4 counts at ART initiation in men could be a consequence of lower CD4 cell counts before HIV acquisition.
Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database
Lim Poh-Lian,Zhou Jialun,Ditangco Rossana A,Law Matthew G
Journal of the International AIDS Society , 2012, DOI: 10.1186/1758-2652-15-1
Abstract: Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits.
Scaling Up Antiretroviral Treatment Services in Karnataka, India: Impact on CD4 Counts of HIV-Infected People  [PDF]
Suresh Shastri, Pavithra Hatna Boregowda, Bharat B. Rewari, Sukarma Tanwar, Anita Shet, Ajay M. V. Kumar
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072188
Abstract: Setting Twelve antiretroviral treatment centres under National AIDS Control Programme (NACP), Karnataka State, India. Objective For the period 2004-2011, to describe the trends in the numbers of people living with HIV (PLHIV) registered for care and their median baseline CD4 counts, disaggregated by age and sex. Design Descriptive study involving analysis of routinely captured data (year of registration, age, sex, baseline CD4 count) under NACP. Results 34,882 (97% of total eligible) PLHIV were included in analysis. The number registered for care has increased by over 12 times during 2004-11; with increasing numbers among females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011 – the increase was greater among females as compared to males. However, about two-thirds still presented at CD4 cell counts less than 350. Conclusion We found an increasing trend of median CD4 counts among PLHIV presenting to ART centres in Karnataka, an indicator of enhanced and early access to HIV care. Equal proportion of females and higher baseline CD4 counts among them allays any fear of differential access by gender. Despite this relative success, a substantial proportion still presented at low CD4 cell counts indicating possibly delayed HIV diagnosis and delayed linkage to HIV care. Universal HIV testing at health care facilities and strengthening early access to care are required to bridge the gap.
CD4 Counts and Viral Loads of Newly Diagnosed HIV-Infected Individuals: Implications for Treatment as Prevention  [PDF]
Sarishen Govender, Kennedy Otwombe, Thandekile Essien, Ravindre Panchia, Guy de Bruyn, Lerato Mohapi, Glenda Gray, Neil Martinson
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090754
Abstract: Objective To report the viral load and CD4 count in HIV-infected, antiretroviral na?ve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines. Design This was a cross-sectional study in a high-volume, free-of-charge HIV testing centre in Soweto, South Africa. Methods We enrolled first time HIV testers and collected demographic and risk-behaviour data and measured CD4 count and viral load. Results Between March and October 2011, a total of 4793 adults attended VCT and 1062 (22%) tested positive. Of the 1062, 799 (75%) were ART na?ve and 348/799 (44%) were first-time HIV testers. Of this group of 348, 225 (65%) were female. Overall their median age, CD4 count and viral load was 34 years (IQR: 28-41), 364 (IQR: 238-542) cells/mm3 and 13,000 (IQR: 2050-98171) copies/ml, respectively. Female first time HIV testers had higher CD4 counts (419 IQR: 262-582 vs. 303 IQR: 199-418 cells/mm3) and lower viral loads (9,100 vs. 34,000 copies/ml) compared to males. Of 183 participants with CD4 count >350 cells/mm3, 62 (34%) had viral loads > 10,000 copies/ml. Conclusions A large proportion of HIV infected adults not qualifying for immediate ART at the CD4 count threshold of 350 cells/mm3 have high viral loads. HIV-infected men at their first HIV diagnosis are more likely to have lower CD4 counts and higher viral loads than women.
CD4 Cell Counts at HIV Diagnosis among HIV Outpatient Study Participants, 2000–2009  [PDF]
Kate Buchacz,Carl Armon,Frank J. Palella,Rose K. Baker,Ellen Tedaldi,Marcus D. Durham,John T. Brooks
AIDS Research and Treatment , 2012, DOI: 10.1155/2012/869841
Abstract: Background. It is unclear if CD4 cell counts at HIV diagnosis have improved over a 10-year period of expanded HIV testing in the USA. Methods. We studied HOPS participants diagnosed with HIV infection ≤6 months prior to entry into care during 2000–2009. We assessed the correlates of CD4 count <200 cells/mm3 at HIV diagnosis (late HIV diagnosis) by logistic regression. Results. Of 1,203 eligible patients, 936 (78%) had a CD4 count within 3 months after HIV diagnosis. Median CD4 count at HIV diagnosis was 299 cells/mm3 and did not significantly improve over time ( ). Comparing periods 2000-2001 versus 2008-2009, respectively, 39% and 35% of patients had a late HIV diagnosis ( ). Independent correlates of late HIV diagnosis were having an HIV risk other than being MSM, age ≥35 years at diagnosis, and being of nonwhite race/ethnicity. Conclusions. There is need for routine universal HIV testing to reduce the frequency of late HIV diagnosis and increase opportunity for patient- and potentially population-level benefits associated with early antiretroviral treatment. 1. Introduction Recent HIV surveillance data suggest that approximately 33% of HIV-infected persons in the United States present for HIV testing late and have AIDS (CD4+ cell count <200?cells/mL or an AIDS-defining illness) within one year after HIV diagnosis [1, 2]. Patients are less likely to experience the full benefits of highly active combination antiretroviral (cART) therapy if they enter HIV care and initiate treatment at a CD4 count <350?cells/mm3 [3, 4]; the clinical cost is even more profound when the CD4 count is <200?cells/mm3 or the patient has already developed clinical AIDS [5–8]. In addition, persons who remain unaware of their HIV-positive status (estimated 21% to 25% of infected persons in the USA in recent years) [9, 10] may not only miss the benefits of earlier cART treatment, but are also more likely to remain chronically viremic and are thereby more likely to transmit HIV to their sexual and needle-sharing partners [9]. The CDC has been promoting strategies to encourage more widespread HIV screening to diagnose infected persons earlier in the course of their illness, including by releasing in 2006 the guidelines for implementing routine universal opt-out testing in healthcare settings [11]. Yet, the latest HIV surveillance data [1, 2] and epidemiologic studies in multiple US populations indicate that the proportion of persons who are diagnosed late in the course of HIV infection [2, 12, 13] or present late for HIV care [14, 15] remains unacceptably high. Stable or worsening
Kiran LJ*, Gokul CG, Santhosh Ramakrishna, Narendranath S
International Journal of Bioassays , 2012,
Abstract: The main objective of the study is 1. To compare the effect of triple drug therapy with stavudine + lamivudine + nevirapine on CD4 counts 6months and 12 months after therapy. 2. To compare the effect of triple drug therapy with zidovudine + lamivudine + nevirapine on CD4 counts 6months and 12 months after therapy. 3. To compare the efficacy of the above two mentioned regimens. Methods: In this retrospective study, data was collected from the antiretroviral therapy (ART) Centre where 46 subjects infected with HIV received stavudine + lamivudine + nevirapine and 54 subjects infected with HIV received zidovudine + lamivudine + nevirapine. Baseline CD4 counts were recorded and compared with CD4 counts after 6 months and 12 months after therapy in each regimen. Changes in CD4 counts in both the regimen were also compared. Statistical analysis was done using ANOVA followed by Tukey test for group wise comparison. Results: Statistical analysis showed that there was no significant change in CD4 count after 6 months of treatment in stavudine group whereas there was significant increase in CD4 counts after 12 months after therapy with stavudine + lamivudine + nevirapine. But there was a significant increase in CD4 counts after both 6 months and 12 months of treatment with zidovudine + lamivudine + nevirapine. But when efficacy of both the regimen was compared with each other there was no significant change in the CD4 counts. Conclusion: This nevirapine and zidovudine + lamivudine + nevirapine are equally efficacious but improvement of CD4 counts after initial 6 months of therapy is better with zidovudine + lamivudine + nevirapine treated group than compared with stavudine + lamivudine + nevirapine treated group.
Cancers in the TREAT Asia HIV Observational Database (TAHOD): a retrospective analysis of risk factors
Petoumenos Kathy,Hui Eugenie,Kumarasamy Nagalingeswaran,Kerr Stephen J
Journal of the International AIDS Society , 2010, DOI: 10.1186/1758-2652-13-51
Abstract: Background This retrospective survey describes types of cancers diagnosed in HIV-infected subjects in Asia, and assesses risk factors for cancer in HIV-infected subjects using contemporaneous HIV-infected controls without cancer. Methods TREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV-related information. For risk factor analyses, two HIV-infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS-defining cancers (ADCs), and non-ADCs. Non-ADCs were further categorized as being infection related (NADC-IR) and unrelated (NADC-IUR). Results A total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC-IURs and NADCs-IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non-Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm3 were approximately 80% less likely to be diagnosed with an ADC (p < 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs-IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs-IR. Conclusions The spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non-Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth-muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.
Immune Activation, Cd4+ T Cell Counts, and Viremia Exhibit Oscillatory Patterns over Time in Patients with Highly Resistant HIV Infection  [PDF]
Christina M. R. Kitchen, Lilit Yeghiazarian, Rebecca Hoh, Joseph M. McCune, Elizabeth Sinclair, Jeffrey N. Martin, Steven G. Deeks
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021190
Abstract: The rates of immunologic and clinical progression are lower in patients with drug-resistant HIV compared to wild-type HIV. This difference is not fully explained by viral load. It has been argued that reductions in T cell activation and/or viral fitness might result in preserved target cells and an altered relationship between the level of viremia and the rate of CD4+ T cell loss. We tested this hypothesis over time in a cohort of patients with highly resistant HIV. Fifty-four antiretroviral-treated patients with multi-drug resistant HIV and detectable plasma HIV RNA were followed longitudinally. CD4+ T cell counts and HIV RNA levels were measured every 4 weeks and T cell activation (CD38/HLA-DR) was measured every 16 weeks. We found that the levels of CD4+ T cell activation over time were a strong independent predictor of CD4+ T cell counts while CD8+ T cell activation was more strongly associated with viremia. Using spectral analysis, we found strong evidence for oscillatory (or cyclic) behavior in CD4+ T cell counts, HIV RNA levels, and T cell activation. Each of the cell populations exhibited an oscillatory behavior with similar frequencies. Collectively, these data suggest that there may be a mechanistic link between T cell activation, CD4+ T cell counts, and viremia and lends support for the hypothesis of altered predator-prey dynamics as a possible explanation of the stability of CD4+ T cell counts in the presence of sustained multi-drug resistant viremia.
CD4 cell counts in adults with newly diagnosed HIV infection in Barbados
Kilaru,Krishna R.; Kumar,Alok; Sippy,Namrata;
Revista Panamericana de Salud Pública , 2004, DOI: 10.1590/S1020-49892004001100002
Abstract: objective: to evaluate the absolute cd4 cell counts of all the newly diagnosed hiv-infected persons who presented at the ladymeade reference unit (lru), which serves as the national hiv/aids referral and treatment center for the country of barbados. design and methods: the study group was comprised of hiv-infected adults who had been diagnosed with hiv infection and referred to the lru between january and december 2002. all the patients referred to the lru had a cd4 cell count done at their first visit to the unit, as part of the routine workup to assess their disease status and need for antiretroviral therapy. results: of the 106 newly diagnosed adults, 62 of them (58.5%) were males, who had a median age at presentation of 40 years; the other 44 of them (41.5%) were females, and their median age at presentation was 36 years. nearly one-fifth (18.2%) of the females were aged 16-25 years, whereas only 8.1% of the males were in this age group. the majority (57.6%) of the study group were diagnosed because they presented with an hiv/aids-related illness. overall, the median cd4 cell count at the time of diagnosis was 183/μl; 52 of 103 adults (50.5%) with a newly diagnosed hiv infection had a cd4 cell count that was <200. among males, the median cd4 cell count was 161/μl, and 32 (53.3%) of 60 males had cd4 cell counts <200. in contrast, among females, the median cd4 cell count was 223, and 20 (46.5%) of 43 females had a cd4 cell count that was <200/μl. however, this difference in the proportion of males and females with a cd4 cell count less than 200/μl was not statistically significant (p = 0.63). conclusions: at the time of hiv diagnosis, over one-half of the adults had an initial cd4 cell count that was consistent with relatively advanced disease. proportionally more women than men presented at a younger age, and proportionally more women than men presented in the early stages of the disease. these patterns indicate a clear need for enhanced educational efforts regar
HIV Patients Developing Primary CNS Lymphoma Lack EBV-Specific CD4+ T Cell Function Irrespective of Absolute CD4+ T Cell Counts  [PDF]
Olivier Gasser,Florian K Bihl,Marcel Wolbers,Elisabetta Loggi,Ingrid Steffen,Hans H Hirsch,Huldrych F Günthard,Bruce D Walker,Christian Brander,Manuel Battegay,Christoph Hess ,for the Swiss HIV Cohort Study
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040096
Abstract: Background In chronic HIV infection, antiretroviral therapy–induced normalization of CD4+ T cell counts (immune reconstitution [IR]) is associated with a decreased incidence of opportunistic diseases. However, some individuals remain at risk for opportunistic diseases despite prolonged normalization of CD4+ T cell counts. Deficient Epstein-Barr virus (EBV)-specific CD4+ T cell function may explain the occurrence of EBV-associated opportunistic malignancy—such as primary central nervous system (PCNS) lymphoma—despite recovery of absolute CD4+ T cell counts. Methods and Findings Absolute CD4+ T cell counts and EBV-specific CD4+ T cell-dependent interferon-γ production were assessed in six HIV-positive individuals prior to development of PCNS lymphoma (“cases”), and these values were compared with those in 16 HIV-infected matched participants with no sign of EBV-associated pathology (“matched controls”) and 11 nonmatched HIV-negative blood donors. Half of the PCNS lymphoma patients fulfilled IR criteria (defined here as CD4+ T cell counts ≥500/μl blood). EBV-specific CD4+ T cells were assessed 0.5–4.7 y prior to diagnosis of lymphoma. In 0/6 cases versus 13/16 matched controls an EBV-specific CD4+ T cell response was detected (p = 0.007; confidence interval for odds ratio [0–0.40]). PCNS lymphoma patients also differed with regards to this response significantly from HIV-negative blood donors (p < 0.001, confidence interval for odds ratio [0–0.14]), but there was no evidence for a difference between HIV-negative participants and the HIV-positive matched controls (p = 0.47). Conclusions Irrespective of absolute CD4+ T cell counts, HIV-positive patients who subsequently developed PCNS lymphoma lacked EBV-specific CD4+ T cell function. Larger, ideally prospective studies are needed to confirm these preliminary data, and clarify the impact of pathogen-specific versus surrogate marker-based assessment of IR on clinical outcome.
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