Incidence and progression of cervical lesions in women with HIV: a systematic global review

Global data on cervical lesion incidence and progression in HIV-positive is essential for understanding the natural history of cervical neoplasia and informing screening policy

A call to action: Addressing the reproductive health needs of women with drug-resistant tuberculosis

Although there is substantial risk to maternal and neonatal health in the situation of pregnancy during treatment for rifampicin-resistant tuberculosis (RR-TB), there is little evidence to guide clinicians as to how to manage this complexity. Of the 49 680 patients initiated on RR-TB treatment from 2009 to 2014 in South Africa, 47% were women and 80% of them were in their reproductive years (15 - 44). There is an urgent need for increased evidence of the safety of RR-TB treatment during pregnancy, increased access to contraception during RR-TB treatment, and inclusion of reproductive health in research on the prevention and treatment of TB.

Severe adverse events during second-line tuberculosis treatment in the context of high HIV Co-infection in South Africa: a retrospective cohort study

Background: According to the World Health Organization, South Africa ranks as one of the highest burden of TB, TB/HIV co-infection, and drug-resistant TB (DR-TB) countries. DR-TB treatment is complicated to administer and relies on the use of multiple toxic drugs, with potential for severe adverse drug reactions. We report the occurrence of adverse events (AEs) during a standardised DR-TB treatment regimen at two outpatient, decentralized, public-sector sites in Johannesburg, South Africa. Methods: We reviewed medical records of the six-month intensive treatment phase for rifampicin-resistant (RR) TB patients registered May 2012 - December 2014. Patients contributed follow-up time until death, loss from treatment, censoring (6 months) or data extraction. A standardized regimen of kanamycin, moxifloxacin, ethionamide, terizidone, and pyrazinamide was used according to national guidelines. AEs were graded using the AIDS Clinical Trial Group scale. We present subhazard ratios from competing risk analysis for time to severe AE, accounting for mortality and loss from treatment. Results: Across the two sites, 578 eligible patient files were reviewed. 36.7 % were categorized as low weight (≤50 kg) at DR-TB initiation. 76.0 % had no history of TB treatment prior to the current episode of RR TB. 26.8 % were diagnosed with RR TB while hospitalized, indicating poor clinical condition. 82.5 % of patients were also HIV positive, of whom 43. 8 % were on ART prior to RR TB treatment and 32.1 % initiated ART with or after RR TB treatment. Median CD4 count was 114.5 (IQR: 45-246.5). Overall, 578 reports of AEs were captured for 204 patients (35.3 %) and 110 patients (19.0 %) had at least one severe AE reported. Patients with at least one AE experienced a median of 3 (IQR: 2-4) AEs per patient. HIV-positive patients with CD4 counts ≤100 cells/mm3 and those newly initiating ART were more likely to experience a severe AE (sHR: 2.76, 95 % CI: 1.30–5.84 and sHR: 3.07, 95 % CI: 1.46–6.46, respectively). Conclusion: Severe AE are common during the first 6 months of RR TB treatment and HIV-positive patients newly initiating ART have the highest subdistribution hazard ratio for severe AE, accounting for the competing risks of death and loss from treatment

Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

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<0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection.ConclusionsDifferences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings

Prospective One Year follow up of HIV infected women screened for cervical cancer using visual inspection with acetic acid, cytology and human papillomavirus testing in Johannesburg, South Africa

BACKGROUND: Cervical cancer is the most common cancer in Sub-Saharan Africa. There are little of HIV-infected women one-year after screening using visual inspection with acetic acid (VIA), HPV or cytology in sub-Saharan Africa. METHODS: HIV-infected women in Johannesburg South Africa were screened one year later by Pap smear, VIA and human papillomavirus (HPV) testing. Women qualified for the 12 month follow-up visit if they had a negative or cervical intra-epithelial neoplasia (CIN) 1 results at the baseline visit. Modified Poisson regression was used to analyse associations between patient baseline characteristics and progression. RESULTS: A total of 688 of 1,202 enrolled at baseline study who were CIN-2+ negative and qualified for a 12 month follow-up visit. Progression to CIN-2+ was higher in women with positive VIA results (12.6%; 24/191) than those VIA-negative (4.4%; 19/432). HPV-positive women at baseline were more likely to progress to CIN-2+ (12.3%; 36/293) than those HPV-negative (2.1%; 7/329). Cytology-positive women at baseline were more likely to progress to CIN-2+ (9.6%; 37/384) than cytology-negative women (2.5%; 6/237). Approximately 10% (10.4%; 39/376) of women with CIN 1 at baseline progressed to CIN 2+. Women who were VIA or HPV positive at baseline were more likely to progress aIRR 1.85, CI 95% (1.46 to 2.36), aIRR 1.41 CI 95% (1.14 to 1.75) respectively. CONCLUSION: Progression to CIN-2+ in HIV-infected women is significant when measured by baseline positive VIA, HPV or Pap and yearly screening by any method should be considered in this population if possible

Injectable and oral contraception and the incidence and progression of cervical disease in HIV-infected women in South Africa

Few data exist regarding the effect of hormonal contraception (HC) on incidence and progression of cervical disease (e.g., cervical dysplasia, squamous intraepithelial lesions, cervical intraepithelial neoplasia) in HIV-infected African women

Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa

ObjectiveTo examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women.MethodsA cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression.ResultsAmong 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels<200/mm3 had a higher prevalence of HPV types 16 (p<0.01) and 66 (p=0.04). No statistical relationship between cervical lesions and HAART use was found.ConclusionThe burden of HPV infection and HSIL was high and correlated with HIV-induced immunosuppression. HPV 16 was the most common type in HSIL and increased in prevalence with greater immune suppression. Prophylactic HPV 16 vaccination could prevent approximately 40% of HSIL cases. Strengthening screening programs is imperative in this population

Cost-effectiveness of using the Cervex-Brush (broom) compared to the elongated spatula for collection of conventional cervical cytology samples within a high-burden HIV setting: a model-based analysis

Abstract 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 (<$0.02) and broom ($0.23) and the probability of detecting cervical dysplasia. NHLS data was used for testing volumes and rates of HIV-positivity, suitability of specimens, and presence of endocervical cells. Expected positivity of Pap smears in HIV-infected women (73 %), odds ratios of the effectiveness of the broom (OR: 1.57), and improved sensitivity when endocervical cells present (OR: 1.89) are from literature. NHLS costs were used for the collection devices and conventional cytology ($4.89). Cost of clinic visit is from WHO CHOICE ($8.36). Results In 2010, 80 % of specimens submitted to NHLS were adequate for evaluation; in 2014, only 54 % met the same criteria. For HIV-infected women, according to the guidelines model, using the wooden spatula costs $6.25 million per year,$16.79 per woman tested. Under intended practice, for each additional HSIL case detected among HIV-infected women, the South African cervical cancer screening programme could save $13.64 (95$13.52 to $13.76) by using the broom as its standard of care collection device through increased collection of endocervical cells and consequent reduction in repeat Pap smears. Conclusion Under a wide range of parameters tested using a simulation model, the more expensive plastic broom could save the South African cervical cancer screening programme money and increase detection of high-grade cervical dysplasia in HIV-infected women compared to the current wooden spatula

Randomized Trial of Time-Limited Interruptions of Protease Inhibitor-Based Antiretroviral Therapy (ART) vs. Continuous Therapy for HIV-1 Infection

Background The clinical outcomes of short interruptions of PI-based ART regimens remains undefined. Methods A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load/ml and CD4 T cell count \u3e450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count \u3e350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints. Results The proportions of CD4 counts \u3e350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm. Conclusion We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur