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Background Invasive cervical cancer is the most common cancer is Sub-Saharan Africa partly due to lack of effective screening programmes and the HIV epidemic. The baseline analysis of a South Africa study comparing three cervical cancer screening methods, i.e. cytology, visual inspection with acetic acid (VIA) and HPV testing in HIV-infected women, has been completed and quality assurance of VIA interpretation was evaluated. Methods HIV-infected women, aged 18–65, were recruited from Johannesburg, South Africa and VIA performed with 5% acetic acid. Nurses received a two-week training on the VIA procedure. VIA interpretation by the nurse and recording of a digital image was performed in real time. The study physician reviewed weekly the digital imaging and recorded their own interpretation of the VIA appearance. Women with a positive VIA and 25% of women with a negative VIA had confirmatory colposcopic biopsy. Sensitivity and specificity for VIA interpretation for cervical intraepithelial neoplasia (CIN)-2 + for both the nurse and the doctor were compared retrospectively. Results 1202 HIV infected women with a median age of 37 years and CD4 of 394 cells/mm3 participated. 45% of the women had a positive VIA result. Sensitivity and specificity for VIA to determine CIN 2+, as performed by the nurse and doctor, was 65.4% (59.7–71.1)/68.5% (65.3–71.7) and 75.5% (70.5–80.4)/68.1(65.0–71.3) respectively. There was no statistical difference in the VIA readings comparing the first 600 VIA interpretation to the final 593 VIA readings [nurse (p = 0.613) or doctors (p = 0.624)]. Evaluating the first 300 VIA to the final 300 results was also similar (p = 0.505 for nurse; p = 0.802 for doctors). Conclusion Throughout the study there was no statistical difference in the sensitivity in interpreting VIA. These results show that after two weeks of training, nurses were consistent in their VIA readings and could accurately predict 65.4% of CIN 2+.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; pConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

Background The prevalence of asymptomatic STIs and urethritis/cervicitis pathogen-associated patient characteristics were determined among patients attending a HIV treatment centre in Johannesburg. Methods Consenting consecutive HIV-infected patients, asymptomatic for symptoms/signs of genital discharge, were screened over 12 months for gonorrhoea, trichomoniasis, chlamydial and Mycoplasma genitalium infections using a real-time PCR assay. Bacterial vaginosis (BV) and Candida were detected by microscopy (women only). Serological assays diagnosed syphilis (RPR/TPPA) and herpes simplex type 2 (IgG ELISA) infections. Patients returned at 2 weeks; those with positive results were treated and given contact slips for partners. If available, patients9 most recent CD4 (83%) and viral load (VL) (60%) results were recorded. Demographic, clinical and behavioural data were collected by nurse-administered questionnaire. A descriptive analysis was conducted to obtain frequency distributions of patient and STI prevalence data. Associations were investigated using the χ 2 test at a 5% level of significance. A multiple logistic regression model was fitted to find factors associated with urethritis/cervicitis pathogens. Results 1109 patients were enrolled (551 men, 558 women). Compared with men, women were younger with a mean age [SD] of 35.0 [7.3] vs 37.9 [7.9] years (p Conclusions Urethritis/cervicitis pathogens were highly prevalent among this asymptomatic population. The benefit of introducing such STI screening programmes to improve reproductive health and HIV prevention efforts requires further study.

Background The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. Methods We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. Results We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Conclusions Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution.

Background HIV-seropositive women have a higher risk of oncogenic HPV infection, cervical neoplasia, and cervical cancer than HIV-seronegative women. As HIV-seropositive women begin to live longer due to effective highly active antiretroviral therapy (HAART), their risk of developing cervical cancer may increase. Little data exist regarding the progression of cervical neoplasia in HIV seropositive women from sub-Saharan Africa.

Background Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution. Methods We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans) or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables. Results In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels). Conclusions Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.

Objective: South Africa has very high rates of both HIV infection and cervical pathology. The management of ASC-H is colposcopy and directed biopsy, but with so many women diagnosed with HSIL and a dearth of colposcopy centres in South Africa, women with cytologic diagnosis of ASC-H may not be prioritized for colposcopy. The aim of this study was to determine if HIV-positive women with a cytologic diagnosis of ASC-H should undergo immediate colposcopy or whether colposcopy can be delayed, within the context of an underfunded health care setting with so many competing health needs. Materials and Methods: A computer database search was performed from the archives of an NGO-administered clinic that offers comprehensive HIV care. All women with a cytologic diagnosis of ASC-H on cervical smears from September 2005 until August 2009 were identified. Histologic follow up was sought in all patients. Results: A total of 2111 cervical smears were performed and 41 diagnosed as ASC-H (1.94%). No histologic follow up data was available in 15 cases. Follow up histologic results were as follows: three negative (11.5%), five koilocytosis and/ or CIN1 (19.2%), ten CIN2 (38.5%) and eight CIN3 (30.8%). There were no cases of invasive carcinoma on follow up. Conclusion: The current appropriate management of HIV-positive women in low-resource settings with a diagnosis of ASC-H on cervical smear is colposcopy, despite the costs involved. In the future and if cost-effective in developing nations, use of novel markers may help select which HIV-positive women can be managed conservatively and which ones referred for more active treatment. More research in this regard is warranted.

SummaryBackgroundHematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease.MethodsThis study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition.ResultsThe frequencies of neutropenia (absolute neutrophil count ≤1.3×109/l), anemia (hemoglobin ≤10g/dl), and thrombocytopenia (platelets ≤125×109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p

Background From 2010 to 2014, approximately 2 million Pap smears from HIV-infected women were submitted to the South African National Health Laboratory Services (NHLS) through the national cervical cancer screening programme. The objective of this analysis was to determine whether using the plastic Cervex brush (“broom”) would be a cost-effective approach to improve cytology specimen quality as compared to the wooden spatula used currently. Methods A decision analysis model was built using the expected adequacy rates for samples collected with the spatula (